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Acinetobacter baumannii causes healthcare-associated infections worldwide. Capsular polysaccharide (CPS) is shown an important virulence factor of A. baumannii both in vitro and in vivo. Capsule locus 2 (KL2) for CPS is the most common KL type and is associated with carbapenem resistance. It is unclear whether KL2 is related to the clinical outcome of invasive A. baumannii infection. Here we had followed patients with A. baumannii bacteraemia prospectively between 2009 and 2014. One-third of the unduplicated blood isolates were randomly selected each year for microbiological and clinical studies. The KL2 gene cluster was identified using polymerase chain reaction. A total of 148 patients were enrolled randomly. Eighteen isolates (12.2%) carried KL2, and 130 isolates (87.8%) didn't. Compared with non-KL2 isolates, KL2 isolates had significantly higher resistance to imipenem, sulbactam, and tigecycline. Compared with the non-KL group, in the KL2 group, the hospital stay before development of bacteraemia was longer (P

Background Patients with invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA), especially those with an elevated minimal inhibitory concentration (MIC) of vancomycin (VA), are likely to have treatment failure and poor outcomes. The aim of this study was to delineate and correlate the genotypes and phenotypes of clinical VA-intermediate S. aureus (VISA) from invasive infections in Taiwan. Methods Between 2006 and 2010, a total of 670 non-duplicate MRSA isolates were collected from patients with invasive infections, mostly from blood, as part of a nationwide antimicrobial surveillance program named Tigecycline in vitro Surveillance in Taiwan. Among them, 10 (1.5%) VISA (VA MIC = 4 mg/L) isolates were identified. Molecular typing with staphylococcal cassette chromosome mec (SCCmec), multilocus sequence typing, staphylococcal protein A (spa), mec-associated hypervariable region (dru), accessory gene regulator (agr), and pulse-field gel electrophoresis, and phenotypic analysis including antibiotic susceptibility testing, gene encoding Panton-Valentine leukocidin (pvl), and superantigenic toxin profiles, were analyzed. Results All but one isolate was defined as molecular health-care-associated MRSA: 6 as SCCmecIII-ST239-spa t037-agrI-dru7 (1 isolate) and dru14 (5 isolates), 2 as SCCmecII-ST5-spa t586-agrII-dru4, and one as SCCmecII-ST89-spa t3520-agrIII-dru7. One isolate was defined as SCCmecIV-ST59-spa t437-agrI-dru8, which was categorized as molecular community-associated MRSA. Five pulsotypes were identified; only one had a positive D-test and 3 were insusceptible to daptomycin (MIC ≧1 mg/L). Five isolates possessed sea-selk-selq, among them 4 belonged to SCCmecIII-ST239-spa t037-agrI. Conclusion In this study, VISA was rarely isolated from invasive MRSA infections, and most cases harbored limited genotypes and corresponding phenotypes.

Background The emergence of concurrent levofloxacin- and trimethoprim/sulfamethoxazole (TMP/SMX)-resistant Stenotrophomonas maltophilia (LTSRSM) in Taiwan is becoming a serious problem, but clinical data analysis on this has not been reported. Methods A matched case-control-control study was conducted to investigate risk factors for LTSRSM occurrence in hospitalized patients. For patients with LTSRSM infection/colonization (the case group), two matched control groups were used: control group A with levofloxacin- and TMP/SMX-susceptible S. maltophilia (LTSSSM) and control group B without S. maltophilia. Besides, tigecycline, ceftazidime, cefepime, ciprofloxacin, gentamicin, amikacin, and colistin susceptibilities in collected LTSRSM and levofloxacin- and TMP/SMX-susceptible S. maltophilia (LTSSSM) isolates were compared. Results From January 2014 to June 2016, 129 LTSRSM from cultured 1213 S. maltophilia isolates (10.6%) were identified. A total of 107 LTSRSM infected patients paired with 107 LTSSSM-, and 107 non-S. maltophilia-infected ones were included. When compared with control group A, previous fluoroquinolone and TMP/SMX use was found to be independently associated with LTSRSM occurrence. When compared with control group B, mechanical ventilation, cerebrovascular disease, and previous fluoroquinolone use were risk factors for LTSRSM occurrence. Eighty-five LTSRSM and 85 LTSSSM isolates were compared for antibiotic susceptibilities; the resistance rates and minimum inhibitory concentrations of tigecycline and ceftazidime were significantly higher for LTSRSM than for LTSSSM isolates. Conclusion The emergence of LTSRSM showing cross resistance to tigecycline and ceftazidime would further limit current therapeutic options. Cautious fluoroquinolone and TMP/SMX use may be helpful to limit such high-level resistant strains of S. maltophilia occurrence.

Purpose Antibiotics are frequently used in patients receiving intermittent or continuous renal replacement therapy (RRT). RRT may alter the pharmacokinetics (PK), as well as the ability to achieve PK/pharmacodynamic (PD) targets. Therapeutic drug monitoring (TDM) could help evaluatedrug exposure and guide antibiotic dosage adjustment. The present review describes recent TDM data on antibiotic exposure and PK/PD target attainment in patients receiving intermittent or continuous RRT, proposing practical guidelines for performing TDM. Methods Studies on antibiotic TDM performed in patients receiving intermittent or continuous RRT published between 2000 and 2020 were searched and assessed. The authors focused on studies that reported data on PK/PD target attainment. TDM recommendations were based on clinically relevant PK/PD relationships and previously published guidelines. Results In total, 2383 reports were retrieved. After excluding non-relevant publications, 139 articles were selected. Overall, 107 studies reported PK/PD target attainment for 24 agents. Data were available for various intermittent and continuous RRT techniques. The study design, TDM practice, and definition of PK/PD targets were inconsistent across studies. Drug exposure and target attainment rates were highly variable. TDM appears necessary to control drug exposure in patients receiving intermittent and continuous RRT techniques, especially for antibiotics with narrow therapeutic margins and in critically ill patients. Practical recommendations can provide insights on relevant PK/PD targets, sampling, and timing of TDM for various antibiotic classes. Conclusion Highly variable antibiotic exposure and target attainment have been reported in patients receiving intermittent or continuous RRT. TDM for aminoglycosides, beta-lactams, glycopeptides, linezolid, and colistin is recommended in patients receiving RRT and suggested for daptomycin, fluoroquinolones, and tigecycline in critically ill patients on RRT.

Background Tigecycline is an antibiotic that well tolerated for treating complicated infections. It has received attention as an anti-cancer agent and expected to solve two major obstacles, sides effects that accompany chemotherapy and drug resistance, in the breast cancer treatment. However, previous studies reported that the levels in the blood are typically low of tigecycline, so higher doses are needed to treat cancer, that may increase the risk of side effects. To achieve better anti-cancer effects for tigecycline, we need to find a novel adjunct agent. Methods In this study, we used different concentration of pyrvinium pamoate combined with tigecycline to treat cell. And assess the effect of two drugs in inhibit cell proliferation, induce cell autophagy, or increase cell apoptosis to evaluate the consequent of combined therapy. Results We observed that after the combined therapy, the cell cycle arrest at G1/s phase, the level of p21 increased, but decreased the levels of CDK2. Others, two drugs via different mechanisms to inhibit cancer cell proliferation and with selective cytotoxic to different cell lines. That could enhance the effect of breast cancer treatment. Conclusion Combining low dose of tigecycline use with pyrvinium pamoate is a novel approach for breast cancer treatment. Appropriate combined therapy in breast cancer is recommended to improve outcomes. Other problems like drug resistance occur in patients or the microbes surrounding breast tissues would confer susceptibility to cancers then influence the effectiveness of treatment, which could be improved through combined therapy.

Purpose: With the emergence of multidrug-resistant and pan-resistant strains, Klebsiella pneumoniae (K. pneumoniae) shows higher treatment failure rates and mortality in clinics. It is more important to develop an effective method for treating K. pneumonia infections. The main objectives of this study were to determine the minimal inhibitory concentration (MIC) and the mutant prevention concentration (MPC) for eight antimicrobial agents against K. pneumoniae isolated from different hosts and compare the emergence of resistant mutants between animal strains and human strains. Materials and Methods: A total of 72 nonduplicate K. pneumoniae isolates and 8 antimicrobial agents (amikacin, azithromycin, levofloxacin, doxycycline, nitrofurantoin, colistin, tigecycline, and imipenem) were used. The MIC and MPC values were determined using agar plate assays. The values of the selection index (SI) were calculated with MPC90/MIC90. Pharmacodynamic parameters were calculated using published plasma pharmacokinetic variables. Results: For human isolate strains, the MPC50/90 (μg/mL) values were as follows: amikacin, 32/128; azithromycin, 64/128; levofloxacin, 4/16; doxycycline, 32/32; nitrofurantoin, 128/512; colistin, 4/8; tigecycline, 8/16; and imipenem, 4/8. The value of SI was 8 for azithromycin, doxycycline, and tigecycline; 16 for amikacin, levofloxacin, and nitrofurantoin; 4 for imipenem; and 2 for colistin. For animal isolate strains, the MPC90 values were 128 μg/mL for azithromycin and doxycycline, 64 μg/mL for amikacin, 32 μg/mL for levofloxacin, 512 μg/mL for nitrofurantoin, 8 μg/mL for colistin and tigecycline, 4 μg/mL for imipenem. The value of SI was 2 for colistin and imipenem, 8 for tigecycline, 16 for amikacin, and 32 for the other four agents. In combination with pharmacokinetic parameters, these findings indicated that the plasma concentrations of the seven antibiotics except imipenem were below the MPC for the entire dosing interval. Conclusion: The ability of eight antibiotics to prevent resistant mutants of K. pneumoniae was different between animal strains and human strains. Higher doses than those currently approved should be required to prevent the enrichment of mutants of drug-resistant bacteria in the clinics.

Актуальність. Бойові поранення кінцівок, кількість яких стрімко зросла з 2014 року, часто ускладнюються розвитком хірургічної інфекції. Сучасною тенденцією є зростання частки неферментуючих грамнегативних паличок серед етіологічних чинників госпітальних хірургічних інфекційних ускладнень. Мета дослідження: обґрунтувати вибір раціональної антибактеріальної терапії та профілактики спричиненої цими мікроорганізмами госпітальної хірургічної інфекції поранень кінцівок. Матеріали та методи. У трьох військово-медичних клінічних центрах (міста Київ, Львів, Вінниця) проведено аналіз результатів бактеріологічних досліджень бойових поранень. Аналіз стійкості до антибіотиків та профілів резистентності проводили відповідно до рекомендацій EUCAST та національних рекомендацій з інфекційного контролю. Порівняння резистентності до окремих препаратів проводили за критерієм Пірсона χ2. Результати. Проаналізовано результати 326 бактеріологічних обстежень, з яких отримано дані про 378 мікроорганізмів. Частка паличок роду Acinetobacter та роду Pseudomonas сягає 40 % серед усього спектра контамінант бойових поранень кінцівок. За станом чутливості до різних хіміотерапевтичних препаратів більшість ізолятів належить до полірезистентних або штамів із розширеною резистентністю. Рекомендації з антибактеріальної терапії госпітальних хірургічних інфекцій, до яких входить монотерапія карбапенемами та комбінації з включенням цефалоспоринів та фторхінолонів, будуть неефективні. До тигецикліну, колістину B та фосфоміцину виявляє стійкість менше від 25 % ізолятів P.aeruginosa та Acinetobacter spp. Виявлено штами з однаковими комбінаціями детермінант стійкості, такі штами виявляються навіть у географічно віддалених госпіталях. ­Висновки. Полірезистентність мікроорганізмів, факти об’єднання штамів в однакові фенотипи резистентності, що виявляються в різних госпіталях, вказують на те, що сучасні бойові поранення контамінуються спорідненими клональними популяціями, які мають єдине госпітальне джерело походження. Розробляти заходи антибактеріальної терапії потрібно в масштабах усього лікувально-евакуаційного ланцюга, без урахування локальних особливостей резистентності.

Background The increase in carbapenem-resistant Klebsiella pneumoniae (CRKP) infections is of great concern because of limited treatment options. New antimicrobials were recently approved for clinical therapy. This study evaluated the epidemiology of carbapenemase-producing K. pneumoniae isolates collected at a Greek university hospital during 2017-2020, and their susceptibilities to ceftazidime-avibactam (CAZ/AVI), meropenem-vaborbactam (M/V), imipenem-relebactam (I/R), eravacycline, plazomicin, and comparators. Methods Minimum inhibitory concentrations (MICs) were evaluated by Etest. Only colistin MICs were determined by the broth microdilution method. Carbapenemase genes were detected by PCR. Selected isolates were typed by multilocus sequence typing (MLST). Results A total of 266 carbapenemase-producing K. pneumoniae strains were isolated during the 4-year study period. Among them, KPC was the most prevalent (75.6%), followed by NDM (11.7%), VIM (5.6%), and OXA-48 (4.1%). KPC-producing isolates belonged mainly to ST258 and NDM producers belonged to ST11, whereas OXA-48- and VIM producers were polyclonal. Susceptibility to tigecycline, fosfomycin, and colistin was 80.5%, 83.8%, and 65.8%, respectively. Of the novel agents tested, plazomicin was the most active inhibiting 94% of the isolates at ≤ 1.5 μg/ml. CAZ/AVI and M/V inhibited all KPC producers and I/R 98.5% of them. All OXA-48 producers were susceptible to CAZ/AVI and plazomicin. The novel β-lactam/β-lactamase inhibitors (BLBLIs) tested were inactive against MBL-positive isolates, while eravacycline inhibited 61.3% and 66.7% of the NDM and VIM producers, respectively. Conclusions KPC remains the predominant carbapenemase among K. pneumoniae, followed by NDM. Novel BLBLIs, eravacycline, and plazomicin are promising agents for combating infections by carbapenemase-producing K. pneumoniae. However, the emergence of resistance to these agents highlights the need for continuous surveillance and application of enhanced antimicrobial stewardship.

BACKGROUND Metal-on-metal (MoM) total hip arthroplasty (THA) has been associated with adverse reactions to metal debris, presenting clinically as pseudotumors. CASE SUMMARY This case report presents a female aged 73 year-old with MoM THA-related pseudotumor. After arthrotomy and bursectomy surgeries, histologic examinations of surgical specimens revealed a specific lymphocyte-dominant immunologic response, now known as aseptic lymphocyte-dominant vasculitis-associated lesion (ALVAL). Due to soft tissue persisting effusion after arthrotomy and bursectomy, revision surgery was then performed with ceramic-on-polyethylene THA. However, revision did not resolve the patient’s symptoms. Here we describe our application of tigecycline sclerotherapy to treat recurrent pseudotumor after revision THA and no recurrence after 24-mo follow-up. CONCLUSION Tigecycline sclerotherapy is safe and effective in the management of recurrent pseudotumor after revision non-MoM THA in ALVAL cases.

Objectives Stenotrophomonas maltophilia MER1, a multidrug resistant (MDR) bacterium was isolated from the wastewater from a hospital, Shandong province, China. We attempted to reveal the genetic determinants related to its striking MDR features for effective treatment to S. maltophilia. Methods Antibiotic susceptibility testing of strain MER1 was performed by using the disk diffusion method on the Mueller-Hinton agar plates, and the minimum inhibitory concentrations (MICs) were determined according to the Clinical Laboratory Standard Institute protocols. The genome of MER1 was sequenced and assembled with a PacBio RS II and a BGISEQ-500 platform. Antibiotic resistance agents together with other transferability or adaptability determinants were identified by comparative genomics. Phylogenetic and contextual assays for these identified elements were conducted to assess the spread risk of MER1. Results Susceptibility testing reveals that strain MER1 is strikingly resistant to nine different antibiotics, including ampicillin, meropenem, amikacin, erythromycin, vancomycin, tetracycline, tigecycline, polymyxin E and ceftazidime. Several genes were identified to encode efflux pumps and inactivation agents accounting for MER1 resistance to above antibiotics, including meropenem, tigecycline and colistin regarded as the last-line therapy for infections caused by multidrug-resistant Gram-negative bacteria. MER1 co-harbors two non-mobile mcr homologs. A novel genomic region of variability was demonstrated to confer bacterial robustness and adaptability upon strain MER1. Conclusion Collective efforts revealed the multiple drug resistance properties and potential genetic determinants of S. maltophilia MER1 isolated from the hospital sewage. Comparative genomic analysis of S. maltophilia MER1 may provide insights into prevention and treatment of its antimicrobial resistance. Our findings would prompt public concern that the MDR genes in the reservoir of S. maltophilia may further spread into various ecological niches or medically high-risk pathogens.

Objectives The mobile tigecycline resistance gene tet(X4), conferring resistance to all tetracyclines, is largely reported from China, however the global spread of such a novel resistance mechanism is a concern for preserving the efficacy of these last-resort antibiotics. The aim of our study was to determine the genetic basis of resistance in a tigecycline-resistant Escherichia coli strain (2-326) isolated from sewage in Bergen, Norway, using whole-genome sequencing (WGS). Methods WGS was carried out using Illumina MiSeq-based sequencing. In vitro conjugation assays were performed to determine the potential of isolate 2-326 to transfer tigecycline resistance to other strains. Results Escherichia coli isolate 2-326 belongs to pathogenic sequence type 167 (ST167) and carries several clinically important antibiotic resistance genes including tet(X4), blaCTX-M-14, dfrA12, sul2, qnrS1 as well as several aminoglycoside resistance genes. Tigecycline resistance along with resistance to tetracycline, sulfamethoxazole, chloramphenicol and azithromycin was transferred to green fluorescent protein (GFP)-encoding E. coli strain CV601-GFP by conjugation. Conclusion To the best of our knowledge, this is the first report of E. coli carrying mobile tet(X4) gene from Norway. Our study demonstrates the ongoing spread of new mechanisms of resistance against last-resort antibiotics and the need for surveillance of such resistance factors in the population in order to mitigate their spread.

Objectives IMP-type carbapenemases are rarely detected in Europe and limited information is available to guide the treatment of infections caused by carbapenemase-producing Enterobacterales (CPE) producing these carbapenemases. Accurate antimicrobial susceptibility testing (AST) results are essential for optimal antibiotic management. Here we report discrepancies in AST of IMP-producing Enterobacterales (IMP-CPE) complicating the management of severe sepsis. Methods Antimicrobial susceptibilities were analysed by in-house VITEK® 2, Etest and broth microdilution (BMD). Carbapenemase-encoding genes were detected by PCR. Whole-genome sequencing (WGS) was performed using an Illumina MiSeq platform. Results Minimum inhibitory concentrations (MICs) determined by VITEK® 2 for Enterobacter hormaechei and Klebsiella oxytoca blood culture isolates were ≥16 mg/L for meropenem and ≤0.5 mg/L for ertapenem. In contrast, Etest analysis and BMD returned MICs of 2 mg/L and 1 mg/L, respectively. Both isolates tested positive for IMP carbapenemase-encoding genes by PCR. WGS revealed that both isolates carried the same blaIMP-4 gene. Based on VITEK® 2 susceptibilities, initial treatment was with tigecycline and amikacin. After subsequent deterioration, the patient was successfully treated with ertapenem and amikacin. Conclusion This case highlights that automated AST by VITEK® 2 can over-report meropenem resistance for IMP carbapenemase-producers compared with Etest and BMD. Clinicians need to be cautious deciding against carbapenem treatment based on VITEK® 2 susceptibility testing results for IMP-positive Enterobacterales. Tigecycline was inferior to carbapenem treatment for pyelonephritis caused by isolates expressing IMP carbapenemases, however specific evidence guiding the treatment of these infections is lacking.

Several antimicrobial combination therapies are used to treat multiple drug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii infections. A novel antibiotic, eravacycline, shows a higher potency than tigecycline. The efficacies of eravacycline-based therapies have not yet been evaluated. We demonstrated the effectiveness of eravacycline- and tigecycline-based combination therapies in XDR and especially tigecycline resistant A. baumannii. Thirteen eligible isolates were selected from 642 non-duplicate Acinetobacter blood isolates from four medical centres in 2010-2014. Tigecycline/imipenem and eravacycline/imipenem combinations were simultaneously effective against some isolates in vitro with fractional inhibitory concentration index of 0.5. In contrast, eravacycline- and tigecycline-based combination therapies provided no additional benefits in mouse survival compared to those for monotherapy. In summary, colistin is still the final resort for XDR-A. baumannii treatment according to the sensitivities. Owning to rapid development of resistance in A. baumannii, novel antibiotics are urgently needed.

Antibiotics resistance is a rapidly emerging issue through the misuse of antibiotics to treat human and animalrelated infections. The use of beta-lactams has increased considerably since its discovery so also resistant genes leading to Extended-Spectrum Beta-Lactamases (ESBL) mediated by the presence of blaCTX-M , blaTEM and blaSHV genes present in most Gram-negative bacteria. This study aimed to detect the widespread distribution of ESBL genes from fomites, healthcare workers, and patients suffering from urinary tract infection in two hospitals in Lagos state, Nigeria. A total of 150 swab samples were collected from fomites, health care workers, and cathetersof patients suffering from urinary tract infection (UTI). Antibiotics susceptibility test was performed by Kirby- Bauer technique according to CLSI guidelines. Organisms that tested positive phenotypically for ESBL were subjected to PCR for molecular analysis. ESBL prevalence rate of 21.8% and a carbapenemase-resistance rate of 16.7% were recorded. The ESBL producing isolates showed the highest resistance to ceftriaxone (82.4%) and the least resistance to tigecycline (5.9%). The existence of blaCTX-M and blaTEM was detected in 76.5% and 17.6% of the isolates respectively, while bla encoding gene was not detected in this study. The distribution of blaSHV genes detected in this study is of great concern which necessitates strict control measures in the usage of antibiotics especially the third-generation cephalosporin. In summary, the presence and distribution of ESBL encoding genes within two hospitals in Lagos were tested and the highest occurrence was recorded in blaCTX-M gene reducing and limiting the available treatment option for infections.

The emergence and spread of plasmid-mediated tigecycline resistance genes have attracted extensive attention worldwide. We investigated the distribution of mobile tigecycline resistance genes in Salmonella genomes generated by both our laboratory and public bacterial genomes downloaded from the NCBI GenBank. The tet(X4)-positive strains were subjected to susceptibility testing and conjugation assays. The genetic features of the tet(X4)-bearing plasmid sequence were analyzed. Here, we report the identification of the plasmid-mediated tigecycline resistance gene tet(X4) in a conjugative plasmid of the Salmonella enterica serovar Llandoff strain SH16G3606, isolated from a man in China in 2016, the first reported serovar Llandoff in China as a novel sequence type ST8300. The tet(X4)-mediated resistance phenotype was successfully transferred from the Salmonella Llandoff strain into Escherichia coli J53, resulting in a 32-fold increase in the minimal inhibitory concentration of tigecycline. The tet(X4) gene was located between two copies of ISCR2 in the plasmid pSal21GXH-tetX4. To our knowledge, this is the first report of the plasmid-mediated tigecycline resistance gene tet(X4) in a Salmonella Llandoff strain isolated from a human stool sample in China. In addition, our findings demonstrated that a total of 171 isolates are carrying tet(X)-like genes distributed in 21 countries or areas across 6 continents, posing a serious threat to humans and public health. Overall, our timely discovery of the recent emergence of the tet(X4) gene in Salmonella isolates and other Enterobacteriaceae bacteria species supports the need for rapid surveillance to prevent the tet(X)-like gene from spreading.

Purpose Hospital-acquired pneumonia (HAP) is becoming a serious problem in China, especially caused by multi-drug resistant (MDR), which is a risk factor for poor prognosis of intracranial cerebral hemorrhage (ICH). We investigate the risk factors for HAP among patients with ICH and study the antibiotic use and medical costs of MDR infection. Methods We performed a retrospective, case–control, parallel study in Xiangya Hospital. Patients included in this study and diagnosed with basal ganglia hemorrhage were admitted between January 2017 and December 2019. Results Univariate analysis discovered some personal risk factors including gender (p = .002), age (p = .023), and underlying conditions such as diabetes (p = .036), coronary heart disease (p = .009), and renal insufficiency (p = .001). Invasive medical operations including endotracheal intubation, tracheotomy, ventilator use, lumbar puncture, urinary catheter insertion, and peripherally inserted central catheter (PICC) (p

SETTING: Nepal Mediciti Hospital, Bhainsepati, Lalitpur, NepalOBJECTIVES: To determine antimicrobial resistance patterns, and the number and proportion of multidrug-resistant (MDR-) and extensively drug-resistant (XDR-) cases among all patients with Acinetobacter isolates between September 2018 and September 2019.DESIGN: This was a hospital laboratory-based, cross-sectional studyRESULTS: Acinetobacter spp. (n = 364) were more common in respiratory (n = 172, 47.3%) and invasive samples such as blood, body fluids (n = 95, 26.1%). Sensitivity to AWaRe (Access, Watch and Reserve) Group antibiotics (tigecycline, polymyxin B, colistin) remained high. MDR (resistance to at least three classes of antimicrobial agents) (n = 110, 30.2%) and XDR (MDR plus carbapenem) (n = 87, 23.9%) isolates were most common in the Watch Group of antibiotics and found in respectively 99 (31.0%) and 78 (24.5%) patients (n = 319). Infected patients were more likely to be aged >40 years (n = 196, 61.4%) or inpatients (n = 191, 59.9%); 76 (23.8%) patients had an unfavourable outcome, including death (n = 59, 18.5%).CONCLUSION: A significant proportion of MDR and XDR isolates was found; nearly one patient in five died. Robust hospital infection prevention and control measures (particularly for respiratory and invasive procedures) and routine surveillance are needed to reduce infections and decrease the mortality rate. Tigecycline, polymyxin B and colistin should be cautiously used only in MDR and XDR cases.

Yu-Ting Huang,1 Chia-I Yu,2 Pao-Yu Chen,3,4 Chi-Chuan Wang,1,2,5 Chien-Chih Wu1,2 1Department of Pharmacy, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; 2School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; 4Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 5Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, TaiwanCorrespondence: Chien-Chih WuDepartment of Pharmacy, National Taiwan University Hospital, College of Medicine, National Taiwan University, 7 Chung Shan S. Road, Taipei, TaiwanTel/Fax +886-2-23123456 ext. 63702/ +886-2-23310930Email 101440@ntuh.gov.twBackground: Antibiotic combination is commonly used to treat multidrug-resistant pathogens. Reports have indicated that tigecycline use is associated with hypofibrinogenemia. However, whether the bleeding risk of tigecycline is higher than that of other antibiotics remains unknown. The aim of this study was to compare the bleeding risk between colistin–tigecycline and colistin–carbapenem treatment.Methods: This retrospective cohort study enrolled adult patients treated with colistin along with tigecycline or carbapenems (doripenem, imipenem–cilastatin, or meropenem) for ˃72 hours during hospitalization. The primary outcome was major bleeding events, which were determined by a hemoglobin drop of ≥ 2 g/d and receipt of blood transfusions with whole blood or packed red blood cells. Multivariate logistic regression was applied to determine risk factors for bleeding events.Results: In total, 106 and 268 patients in the colistin–tigecycline and colistin–carbapenem groups met the criteria for analysis, respectively. The two groups did not differ significantly in demographic data, except for alanine aminotransferase (ALT), serum creatinine (SCr) and ulcer disease. The colistin–tigecycline group had a higher ALT, SCr and a lower proportion of ulcer disease. Major bleeding events did not differ significantly between the colistin–tigecycline and colistin–carbapenem groups (12.26% vs 9.33%, P = 0.40). Antibiotic duration [OR = 1.06 (1.02– 1.11), P=0.007)] and anticoagulant use [OR = 2.16 (1.05– 4.42), P=0.04] were associated with major bleeding events.Conclusion: Colistin–tigecycline treatment was not associated with a higher bleeding risk. Antibiotic duration and concurrent use of anticoagulant were the risk factors of bleeding events.Keywords: tigecycline, carbapenems, bleeding events

Background: In Taiwan, carbapenem-resistant Klebsiella pneumoniae (CRKP) now became a leading cause of difficult-to-treat healthcare-associated infection, for which there are a lack of recent hospital epidemiological studies on risk factors, mortality, and antimicrobial susceptibility. Methods: We prospectively enrolled patients with healthcare-associated CRKP monomicrobial bloodstream infection (mBSI) and matched patients with carbapenem susceptible K. pneumoniae (CSKP) mBSI at National Taiwan University Hospital (Taipei, Taiwan) from October 2017 through December 2019 in a 1:2 ratio. Multivariable logistic regression and Kaplan–Meier analyses were applied to identify factors associated with CRKP mBSI and to compare the 14-day survival curves, respectively. We detected the presence of blaKPC and blaNDM gene among the included CRKP strains, and performed antimicrobial susceptibility testing (including susceptibility to colistin, aminoglycoside, tigecycline, and ceftazidime/avibactam). Results: A total of 36 CRKP cases and 72 CSKP controls were enrolled. Patients with CRKP mBSI were more likely to have liver cirrhosis (adjusted odds ratio [aOR], 5.61; P = 0.024), length of hospital stay over the previous 14 days (aOR, 1.23; P = 0.001) and prior use of carbapenems in the previous 14 days (aOR, 6.07; P = 0.004) than patients with CSKP mBSI. The 14-day survival was significantly worse for patients with CRKP mBSI than those with CSKP mBSI (all CRKP cases: 50.0% vs. 87.5%; P

Introduction The aim of the present study was to assess the safety profile and outcomes of a ceftazidime–avibactam (CAZ-AVI)-based regimen and compare them with those of a tigecycline (TGC)-based regimen in intensive care unit (ICU) for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP), which is classified into hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Methods Clinical and microbiological cure rates, 28-day survival rates, and safety evaluation findings were compared between patients treated with CAZ-AVI-based regimen and those treated with TGC-based regimen in this retrospective study. Conventional multivariate logistic regression analysis and regression adjustment analysis with propensity score (PS) were performed to control for confounding variables. Results A total of 105 cases of critically ill ICU patients with CRKP-induced HAP or VAP were included in the present study from July 2019 to September 2020; 62 patients (59%) received TGC-based regimen and 43 patients (41%) received CAZ-AVI-based regimen. The most common concomitant agent in the CAZ-AVI group and TGC group was carbapenem (44.2% versus 62.9%, P = 0.058), while only a small proportion of the study population received CAZ-AVI and TGC monotherapy (20.9% versus 6.5%, P = 0.027). The clinical and microbiological cure rates of the CAZ-AVI group were superior to those of the TGC group [51.2% versus 29.0% (P = 0.022) and 74.4% versus 33.9% (P

The aim of this study was to investigate the presence of colistin- and/or tigecycline-resistant Klebsiella spp. in influents from four wastewater treatment plants (WWTPs), which partly reflect the gut microbiome of human populations. Colistin- and tigecycline-resistant Klebsiella pneumoniae isolates (K30/ST29) were detected four times from the WWTP A during a period of 3 months. Disruptions of the mgrB and ramR genes by ISEc68 and ISKpn21, respectively, were identified in those four isolates. They also shared the IncL/M 86,197-bp plasmids carrying a bla(CTX-M-3) and Tn1548-associated armA [IS26-IntI1-dfrA12-gucF-aadA2-qacE Delta 1-sul1-ISCR1-ISEc28-armA-ISEc29-msr(E)-mph(E)-IS26]. Those isolates formed a distinct cluster within wgMLST clusters of ST29 K30 public reference strains of human origin and were unique due to harboring of Tn21-like mercury resistance operon transposons in addition to silver, copper, and arsenic resistance determinants. Five K. pneumoniae strains with different STs and 1 Klebsiella quasipneumoniae strain, exhibiting colistin resistance, were detected in WWTPs B, C, and D. For these isolates, disruptions of mgrB by ISEc68 (three isolates) or ISEcl1 (one isolate), insertion of IS2 in the mgrB promoter region (one isolate), and inactivation of MgrB by a nonsense mutation (one isolate) were identified. Close monitoring of these mcr-negative colistin- and/or tigecycline-resistant bacteria in wastewater influents is imperative to avoid further limiting of treatment options., Article, Microbial Drug Resistance 27(10) : 1433-1442(2021)

ObjectivesTo characterize a novel plasmid-mediated tigecycline resistance-related gene, tet(Y), in a clinical Acinetobacter baumannii isolate from China.MethodsThe tet(Y)-encoded tigecycline-resistant A. baumannii 2016GDAB1 was screened through antimicrobial susceptibility testing and WGS. The function of tet(Y) was verified by complementation of tet(Y). The plasmid transferability and stability were detected via plasmid conjugation and in vitro bacterial passaging. The 3D structure of Tet(Y) was predicted and docked using tFold and AutoDock Vina.ResultsThe tigecycline-resistant A. baumannii 2016GDAB1 was isolated from bronchoalveolar lavage fluid of a patient with hospital-acquired pneumonia. However, this strain did not harbour any common tigecycline resistance genes, determinants or mutations. 2016GDAB1 belongs to the non-epidemic clone ST355 (Oxford scheme), which has been mainly reported in animals. The tet(Y) gene was located on a 72 156 bp plasmid and genomic environment analysis revealed that Tn5393 may play a role in tet(Y) transmission, whereas phylogenetic analysis indicated the origin of tet(Y) as from Aeromonas. Overexpression of tet(Y) resulted in a 2- to 4-fold increase in tigecycline MIC. Introduction of the tet(Y)-harbouring plasmid p2016GDAB1 via electroporation resulted in a 16-fold increase in tigecycline MIC but failed to transfer into the tigecycline-susceptible A. baumannii recipient via conjugation. Isolates carrying the tet(Y) gene were vulnerable to tigecycline pressure and exhibited decreased susceptibility to tigecycline. A tet(Y)-carrying plasmid was stably maintained in the host strains.ConclusionsThis study identified the tigecycline resistance-related gene tet(Y) in A. baumannii. This gene conferred an increased tigecycline MIC and the transposable element Tn5393 may play a role in its transmission across isolates.

Acinetobacter baumannii (A. baumannii) has developed several resistance mechanisms. The bacteria have been reported as origin of multiple outbreaks. This study aims to investigate the use of efflux pumps and quinolone resistance-associated genotypic mutations as mechanisms of resistance in A. baumannii isolates at a tertiary hospital. A total number of 103 A. baumannii isolates were investigated after identification and antimicrobial susceptibility testing by VITEK2 followed by PCR amplification of blaOXA-51. Conventional PCR amplification of the AdeABC efflux pump (adeB, adeS, and adeR) and quinolone (parC and gyrA) resistance genes were performed, followed by quantitative real-time PCR of AdeABC efflux pump genes. Phenotypic evaluation of efflux pump expression was performed by determining the difference between the MIC of tigecycline before and after exposure to an efflux pump inhibitor. The Sanger sequencing method was used to sequence the parC and gyrA amplicons. A phylogenetic tree was drawn using MEGA 4.0 to evaluate evolutionary relatedness of the strains. All the collected isolates were blaOXA-51-positive. High resistance to almost all the tested antibiotics was observed. Efflux pump was found in 75% of isolates as a mechanism of resistance. The study detected parC gene mutation in 60% and gyrA gene mutation in 85%, while 37% of isolates had mutations on both genes. A minimal evolutionary distance between the isolates was reported. The use of the AdeABC efflux pump system as an active mechanism of resistance combined with point mutation mainly in gyrA was shown to contribute to broaden the resistance spectrum of A. baumannii isolates.

OBJECTIVES: The aim of this study was to determine the prevalent aerobic vaginal bacteria and their antibiogram to commonly prescribed antibiotics for the treatment of aerobic vaginitis (AV). METHODOLOGY: A total of 200 high vaginal swabs (HVS) samples were collected from different AV suspected patients visiting Khyber Teaching Hospital (KTH) and processed for identification of bacterial isolates followed by antibiotic susceptibility patterns as per CLSI protocols. RESULTS: Out of 200 clinical samples, 70 (35%) HVS isolates yielded bacterial growth. Of the isolates, E.coli was the common pathogen 36 (51.4%) followed by S.aureus 20 (28.5%), Enterobacter spp 08 (11.4%), Pseudomonas spp 04 (5.7%) and Citrobacter spp 02 (2.8%). The highest prevalence was observed in the age group of 21-35 years (31.4%) followed by age groups 16-20 years (25.7%) and 26-30 years. S.aureus isolates (n=20) were resistant to ciprofloxacin (90%), cephradine (70%), erythromycin (70%), gentamicin (50%) and cefotaxime (40%) while 1 (5%) of each isolate was resistant to methicillin and vancomycin. Majority of the gram-negative isolates (n=50) were resistant to cotrimoxazole, cephalosporins, quinolones, aminoglycosides and susceptible to carbapenems, tigecycline, sulbactam and tazobactam. CONCLUSION: Aerobic vaginitis should be treated very selectively in order not to kill the beneficial bacteria. Before treating AV, the causative agents should be accurately identified and tested for drug susceptibility patterns and empirical antibiotic therapy should be avoided.

Background: The emergence and wide global spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates are of great concern, and the aim of this study was to investigate drug resistance, molecular epidemiology, and genetic relationship of CRKP isolates from patients in Shanghai, China. Methods: A retrospective study was conducted from April 2018 to July 2019, and a total of 133 CRKP isolates were collected. Antimicrobial susceptibility was determined by VITEK-2 automated microbiology analyzer platform (bioMerieux, France) and the broth microdilution method. Polymerase chain reaction assays were used to investigate the presence of drug resistance genes. A modified carbapenem inactivation method was performed to detect carbapenemases. Multilocus sequence typing and pulsed-field gel electrophoresis (PFGE) were conducted for genetic relatedness of 50 CRKP isolates selected. Results: Among 670 isolates of K. pneumoniae, 133 (19.9%) strains were identified as CRKP, of which, 76.7% (102/133) strains were isolated from intensive care units (ICUs). All the 133 CRKP isolates were found to be carbapenemase-producers and harbor blaKPC-2 gene. No other carbapenemase genes of blaNDM, blaOXA-48, blaVIM, and blaIMP were detected. Furthermore, β-lactamase genes of blaSHV, blaCTX, and blaTEM were the most common resistance-associated genes among these KPC-2 producing isolates. All the 133 CRKP strains displayed >95% of resistance to cephalosporins and carbapenems, except for gentamicin, trimethoprim-sulfamethoxazole, amikacin, tigecycline and colistin, and ceftazidime-avibactam. The most common sequence type was ST11, accounting for 90.0% of the 50 CRKP selected, followed by ST15 (10.0%). PFGE analysis clustered the 50 KPC-2-producing isolates into seven (A-G) distinct clonal clusters at 85% cutoff. Of which, A and G were the two major clusters, accounting for the majority of the strains collected in emergency ICU and neurosurgical ICU. And all the strains of clusters D and E were collected in cardiothoracic surgery ICU, except for one strain collected in one outpatient. Conclusion: The KPC-2-producing K. pneumoniae belonged to ST11 was widely disseminated in ICUs, and active and effective surveillance of infection control strategies was initiated to limit the spread of CRKP strains.

Huaiyu Jia,1 Ying Zhang,2 Jianzhong Ye,1 Wenya Xu,1 Ye Xu,1 Weiliang Zeng,2 Wenli Liao,1 Tao Chen,1 Jianming Cao,2 Qing Wu,1 Tieli Zhou1 1Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2Department of Medical Laboratory Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Tieli Zhou; Qing WuDepartment of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaTel/Fax +86-0577-8668-9885Email wyztli@163.com; wuqing830@163.comBackground: OXA-232-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) has the potential to become the “third epidemic” of carbapenem-resistant Klebsiella strain after KPC-2 and NDM in China. We investigated the first outbreak of CRKP in the First Affiliated Hospital of Wenzhou Medical University.Methods: We collected 610 clinical isolates of CRKP from the First Affiliated Hospital of Wenzhou Medical University between January 2019 and September 2020 and screened them by Polymerase Chain Reaction (PCR). The multilocus sequence typing and pulsed-field gel electrophoresis were used to determine the genetic relatedness of the strains. The antimicrobial susceptibility test was performed to determine the drug resistance of the clinical isolates. The molecular mechanism underlying carbapenem resistance was elucidated by performing PCR and conjugation experiments. The virulence potential of the strains was determined by the string test, detection of virulence-associated genes and capsular serotypes, and Galleria mellonella larval infection model.Results: Between September 2019 and May 2020, 26 OXA-232-producing CRKP were obtained from 12 patients in our hospital. Ten patients were hospitalized in the intensive care units (ICU) and the overall mortality of the inpatients involved in the outbreak was 50% (6/12). Epidemiological investigations reported that all the OXA-232-producing CRKP strains belonged to the sequence type ST15 and can be clonally transmitted among the inpatients in the ICU. All the strains had low virulence and were resistant to commonly used clinical antibiotics except for ceftazidime/avibactam, colistin, and tigecycline. The OXA-232-producing CRKP was sensitive to triclosan and chlorhexidine, and its eradication from our hospital can be achieved by the use of disinfectants in the ICU.Conclusion: In our study, OXA-232-producing CRKP isolates appeared to be clonally transmitted and the sequence type ST15 was responsible for the outbreak. Therefore, effective measurements for the infection control of CRKP are urgently needed to prevent its epidemic in the nearby region in the future.Keywords: Klebsiella pneumoniae, carbapenem-resistance, virulence, OXA-232, outbreak

Background Delafloxacin is a novel fluoroquinolone with broad antibacterial activity against pathogens causing acute bacterial skin and skin structure infections (ABSSSI). This network meta-analysis (NMA) was conducted to evaluate the relative efficacy of delafloxacin versus other comparators used for managing patients with ABSSSI. Methods A systematic literature review was conducted to identify randomised controlled trials (RCTs) evaluating adults (≥ 18 years) with ABSSSI, complicated SSSI (cSSSI), complicated skin and soft tissue infections (cSSTI) or severe cellulitis with pathogen of gram-positive, gram-negative, or mixed aetiology. OVID MEDLINE®, Embase, Epub Ahead of Print, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews were searched from inception through 12 April 2019. A feasibility assessment was conducted, followed by an NMA, which was run in a Bayesian framework. The interventions included in the NMA encompassed monotherapy or combination therapies of amoxicillin/clavulanate, ampicillin/sulbactam, ceftaroline, ceftobiprole, dalbavancin, daptomycin, delafloxacin, fusidic acid, iclaprim, linezolid, omadacycline, oxacillin + dicloxacillin, standard therapy, tedizolid, telavancin, tigecycline, vancomycin, vancomycin + aztreonam and vancomycin + linezolid. Results A feasibility assessment was performed and evidence networks were established for composite clinical response (n = 34 studies), early clinical response (n = 16 studies) and microbiological response (n = 14 studies) in the overall study population, composite clinical response (n = 4 studies) in obese subpopulation and for composite clinical response (n = 18 studies) and microbiological response (n = 14 studies) in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. Delafloxacin performed significantly better than fusidic acid, iclaprim, vancomycin, and ceftobiprole for composite clinical response. Delafloxacin was comparable to dalbavancin, daptomycin, fusidic acid, iclaprim, linezolid, omadacycline, tedizolid, vancomycin, vancomycin + aztreonam and vancomycin + linezolid in the analysis of early clinical response, whereas for microbiological response, delafloxacin was comparable to all interventions. In the obese subpopulation, the results favoured delafloxacin in comparison to vancomycin, whilst the results were comparable with other interventions among the MRSA subpopulation. Conclusions Delafloxacin is a promising new antibiotic for ABSSSI demonstrating greater improvement (composite clinical response) compared to ceftobiprole, fusidic acid, iclaprim, telavancin and vancomycin and comparable effectiveness versus standard of care for all outcomes considered in the study.

Introduction: Fosfomycin has re-emerged as a possible therapeutic alternative for the treatment of resistant bacterial pathogens. Its main mechanism of action is the inhibition of the initial step of cell wall synthesis and is active against both Gram-positive and Gram-negative bacteria. However, its clinical effectiveness against multidrug resistant bacteria remains largely unknown. Therefore, we aim to evaluate the clinical and microbiological effectiveness of intravenous fosfomycin as well as its safety in a tertiary care teaching hospital in Lebanon. Methodology: This is a retrospective chart review of adult patients who had presented to the hospital and were treated with intravenous fosfomycin for at least 24 hours for any type of infection between 2014 and 2019. Results: Among 31 episodes treated with intravenous fosfomycin, 68% had an overall favorable clinical response. In 84% of the episodes, fosfomycin was administered in combination with other antibiotics, commonly tigecycline. Of those with available cultures at end of therapy, 73% achieved microbiological success. No relapse was documented within 30 days of completion of therapy. In the episodes secondary to resistant pathogens, the rates of favorable clinical outcome and microbiological success at the end of therapy were 71% and 73%, respectively. Fosfomycin resistance developed in two cases and mild adverse events occurred in 65% of the episodes during the course of treatment. Conclusions: Fosfomycin is a safe and effective option in the treatment of multi-drug resistant infections. Nevertheless, careful stewardship is important to maintain its efficacy and to reduce the risk of selection of antimicrobial resistance.

Introduction: Pyogenic wound infections are the one of the leading cause of morbidity and mortality worldwide. Some of the common etiological agents responsible are Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Klebsiella app., Proteus spp., Pseudomonas spp., and Acinetobacter spp. The antimicrobial resistance has become a global challenge and the resistant pathogen poses a grave threat to the public health worldwide. Pyogenic bacteria producing biofilm has a potential to cause significant mortality and morbidity in human. Aim: The present study was carried out to determine the bacteriological spectrum of wound infections and their antibiogram to commonly used antibiotics and to detect the biofilm production by the isolates. Materials and Methods: This cross sectional study was carried out in the department of Microbiology, Adichunchanagiri institute of Medical sciences from September 2016 to August 2017. Two hundred and forty samples from various wounds were collected and processed as per standard procedures and biofilm production was detected by Congo red agar method. Results: Out of 240 pus isolates, Staphylococcus species were the most commonly isolated (48.85%) followed by Pseudomonas species (11.7%). Biofilm was produced by 49.2% isolates .Majority of Gram negative bacilli were susceptible to Colistin (100%) followed by Tigecycline (Biofilm producers 75%, biofilm non producers 66.7%).All Gram positive isolates were susceptible to Vancomycin and Teicoplanin (100%) followed by Linezolid (biofilm producer 98.8%, biofilm non producer 97.8%) . Conclusion: Routine surveillance for wound infections along with early identification and adopting efficient control protocol against biofilm forming organism plays an important role in the prevention of the most serious infections. Keywords: Antibiotic resistance, Biofilm, Congo red agar, Wound infection

Carbapenem-resistant Acinetobacter baumannii (CRAB) has been a common pathogen of nosocomial infections and severely threatened the public health for decades. Tigecycline is a new type of antibacterial glycylcycline and minocycline derivative and has been used to treat CRAB in clinical practice. However, the synergistic effects of tigecycline in combination with other antibiotics including colistin or amikacin remain unclear. A total of 216 CRAB isolates were collected from multiple body parts of different patients. The gene types of these isolates were analyzed and their resistance to carbapenems was determined by Etest. Broth microdilution method was utilized to evaluate the minimum inhibitory concentration (MIC) of each sample. Checkerboard screening technique was performed to demonstrate the synergistic effects of antibiotics and fractional inhibitory concentration index (FICI) was established. Therefore, the joint treatment of tigecycline and colistin (1:1) could effectively improve the sensitivity of AB to antibiotics. OXA-24-like isolates were more sensitive to the combination of tigecycline and amikacin. On the other hand, OXA-23-like isolates were more sensitive to the combination of tigecycline and colistin. Tigecycline exhibited synergistic effects with amikacin and colistin to inhibit CRAB.

Objectives This study reports antimicrobial activity for ceftaroline and comparators against bacterial isolates from patients with skin and skin structure infections (2015–2018). Methods A central laboratory performed susceptibility testing according to CLSI broth microdilution methodology. EUCAST breakpoints were used. Results Isolates were collected in Europe, 14,408 isolates (53.9%); Asia/South Pacific (SP), 5,317 (19.9%); Latin America, 4,268 (16.0%); and Africa/Middle East (ME), 2,753 (10.3%). In all regions, all 7,950 methicillin-susceptible Staphylococcus aureus (MSSA) isolates were susceptible to ceftaroline and vancomycin; susceptibility to daptomycin, linezolid, teicoplanin, and tigecycline was ≥99.6%. Susceptibility of all 9,174 methicillin-resistant S. aureus (MRSA) isolates to daptomycin, linezolid, teicoplanin, tigecycline and vancomycin was ≥97.7%, with 90.8%–96.5% susceptible to ceftaroline. The ceftaroline MIC90 was 0.008 mg/L against Streptococcus pyogenes, 0.015–0.03 mg/L against Streptococcus agalactiae, and 0.008–0.015 mg/L against Streptococcus dysgalactiae. All β-hemolytic streptococci were susceptible to vancomycin. Susceptibility of extended-spectrum β-lactamase (ESBL)-negative Escherichia coli to ceftaroline ranged from 67.0% in Asia/SP to 91.0% in Africa/ME; susceptibility to amikacin, meropenem and tigecycline was ≥96.7% in all regions. Susceptibility of ESBL-negative Klebsiella pneumoniae to ceftaroline ranged from 78.4% in Europe to 83.2% in Africa/ME, and among ESBL-negative Klebsiella oxytoca was 76.3% in Asia/SP, and 89.0%–93.5% in the other regions. Among ESBL-negative K. pneumoniae and ESBL-negative K. oxytoca, susceptibility was highest to amikacin (93.7%–96.4% and 95.7%–100%, respectively) and meropenem (89.7%–97.4% and 98.3%–100%, respectively). Conclusions Ceftaroline was active against the Gram-positive isolates collected; susceptibility of ESBL-negative Gram-negative isolates showed regional variations.

Background Antimicrobial resistance (AMR) of non-fermenting Gram-negative bacteria (NFGNB) is increasingly recognized as urgent healthcare threat. Trend data on AMR of NFGNB in Saudi Arabia are either old or limited. The objective was to estimate the prevalence and resistance trends of isolated NFGNB in Saudi Arabia. Methods A retrospective multicenter study involving seven tertiary care hospitals in Saudi Arabia was conducted between 2011 and 2016. Susceptibility testing for non-duplicate isolates was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines in College of American Pathologists accredited diagnostic microbiology laboratories in the participating hospitals. Results Out of 461,274 isolates, 100,132 (21.7%) were NFGNB which represented 30% of gram-negative pathogens. Pseudomonas aeruginosa was the most common (73.6%), followed by Acinetobacter baumannii (21.0%) and Stenotrophomonas maltophilia (5.3%). Resistance trends of P. aeruginosa were increasing for aztreonam (absolute increase during the study was 17.3%), imipenem (12.3%), and meropenem (11.6%). A. baumannii was fully resistant to several beta lactam drugs, and resistance trends were increasing for potential treatments such as tigecycline (25.1%) and tobramycin (15.5%). S. maltophilia was >90% resistant to trimethoprim/ sulfamethoxazole and ciprofloxacin by the end of the study. Conclusion We are reporting high and/or increasing resistance of NFGNB to common treatment options. The current findings call for urgent actions to combat the increasing resistance of NFGNB. Large scale sharing of AMR data collected at different hospitals with the Saudi AMR committee would be critical to set priorities and monitor progress.

Objective: To assess Bacterial spectrum and antimicrobial pattern of Blood Stream Infections associated with non-tunneled double lumen catheter in hemodialysis patients. Study Design: Prospective observational study. Place and Duration of Study: Department of Nephrology, Pakistan Emirates Military Hospital Rawalpindi Pakistan; Armed Forces Institute of Pathology Rawalpindi, Pakistan, from May 2019 to Apr 2020. Methodology: A total of 753 patients underwent placement of non-tunneled double lumen catheter (457 femoral, 296 Internal Jugular). Patients with clinically suspected bloodstream infections had their catheters removed with tips being sent for culture along with 2 sets of peripheral blood cultures. Patients were labelled as having bloodstream infection if growth of organism was detected in catheter tip and at least one peripheral blood culture. Susceptibility testing was done for available antimicrobials. Results: One hundred and thirty six (18.06%) incidences or 5.48 bloodstream infections per 1000 catheter days, with confirmed growth on blood cultures were identified. Gram positive infections were seen in 76 (55.88%) individuals with most common organism being coagulase-negative Staphylococcus (28.68%), followed by Staphylococcus aureus (21.32%). These organisms had low resistance rates to Vancomycin (0%), Tigecycline (0%), Doxycycline (6.6%) and Linezolid (9.5%). Gram negative infections were seen in 60 (44.11%) patients with Klebsiella pneumoniae (13.24%) being the most commonly identified pathogen followed by Acinetobacter baumannii (12.50%) and had relatively higher degree of antimicrobial resistance. Conclusion: Gram positive organisms were the most common cause of bloodstream infection in this study and were found susceptible to vancomycin and doxycycline whereas gram-negative organisms had high rates of antimicrobial......

Acinetobacter baumannii (A. baumannii) is an important nosocomial pathogen, which may be a causative agent in a wide-range of human pathologies. Carbapenems are usually considered the last safe and effective choice of drugs for the treatment of Gram-negative infections. The emergence of carbapenem-resistant A. baumannii (CRAB) is a critical public health issue as they leave clinicians with limited therapeutic options. In this study, phenotypic methods were used to characterize sixty-two (n = 62) A. baumannii isolates, which were included based on their suspected non-susceptibility to meropenem. Minimum inhibitory concentrations (MICs) of meropenem, levofloxacin, gentamicin, sulfamethoxazole/trimethoprim, tigecycline were determined using E-tests, while colistin MICs were determined using broth microdilution. The isolates were subjected to the modified Hodge test (MHT), the modified carbapenem-inactivation method (mCIM) and the imipenem/EDTA combined disk test (CDT). Efflux pump overexpression was studied using agar plates containing phenylalanine-arginine β-naphthylamide (PAβN). Assessment of biofilm-formation was carried out using the crystal violet tube-adherence method. 64.5% of the strains showed meropenem MICs in the resistant range (>8 mg/L), resistance rates were similarly high to the other tested antibiotics. The MHT and mCIM assay were positive in 79.0% and 67.7% of cases, respectively; the presence of an MBL was suggested for 29.0% of isolates. Efflux-pump overexpression was seen in 12.9% of isolates. 54.8% of the isolates were characterized as strong biofilm-producers. Microbiology laboratories have an important role in differentiating the distinct mechanisms by which these pathogens develop the CRAB phenotype, as plasmid-borne carbapenemases are significant from the standpoint of public health microbiology.

Introduction Tigecycline is a potential alternative to trimethoprim–sulfamethoxazole in treating Stenotrophomonas maltophilia infections due to its potent in vitro antimicrobial activity. Clinical evidence regarding the use of tigecycline in the treatment of S. maltophilia infections is scarce. In this study, we assessed the efficacy of tigecycline treating ventilator-associated pneumonia (VAP) due to S. maltophilia in comparison with fluoroquinolones. Methods This is a multicenter retrospective cohort study of patients admitted between January 2017 and December 2020 with the diagnosis of VAP caused by S. maltophilia receiving either tigecycline or fluoroquinolones as the definitive therapy ≥ 48 h. Clinical outcomes including 28-day mortality, clinical cure and microbiological cure were analyzed. Results Of 82 patients with S. maltophilia VAP included, 46 received tigecycline, and 36 received fluoroquinolones; 70.7% of patients had polymicrobial pneumonia, and the appropriate empiric therapy was applied to only 14.6% of patients. The overall 28-day mortality was 39%. Compared with patients receiving fluoroquinolones, tigecycline therapy resulted in worse clinical cure (32.6% vs. 63.9%, p = 0.009) and microbiological cure (28.6% vs. 59.1%, p = 0.045), while there was no statistical difference between 28-day mortality (47.8% vs. 27.8%, p = 0.105) in the two groups. Similar results were also shown in the inverse probability of treatment weighted univariable regression model and multivariable regression model. Conclusions The standard dose of tigecycline therapy was associated with a lower clinical and microbiological cure rate but not associated with an increased 28-day mortality in patients with S. maltophilia VAP compared with fluoroquinolones. Considering the unfavorable clinical outcomes, we therefore recommend against using the standard dose of tigecycline in treating S. maltophilia VAP unless new clinical evidence emerges. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00516-5.

Objective Osteoradionecrosis of the jaw (ORNJ) is one of the most common and serious complications after radiotherapy of head and neck malignancies due to the high incidence of nasopharyngeal cancer in Southern China. Clinicians lack understanding and consensus on anti-infective treatment in ORNJ lesions. This research aims to provide evidence for rational use of antibiotics by reviewing the bacterial spectrums and antimicrobial susceptibility test of ORNJ patients. Methods We collected patient who was diagnosed with ORNJ from November 2012 to June 2019 in our hospital. Exudate or bone unexposed wound surface sampling, agar plates culturing and susceptibility testing were analyzed. Descriptive statistics were used for data presentation. Results A total of 219 samples were collected in our retrospective study. The most common cultured bacteria were Klebsiella Pneumoniae (15.10%), Pseudomonas aeruginosa (13.54%) and Staphylococcus aureus (10.94%). Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 5.21% in the whole positive samples. Ticarcillin, Ofloxacin, Vancomycin, Tigecycline, Meropenem were more susceptible than other antibiotics to treat uncontrollable infection. Conclusions Our research provided objective evidence for understanding the types of local bacterial flora and drug susceptibility in ORNJ lesions, and gave a guiding reference for empirical antibiotics medication.

Aims: To develop and validate a new, simple, rapid, precise and accurate Reverse Phase High Performance Liquid Chromatographic (RP-HPLC) method for the quantitative determination of Tigecycline in bulk and pharmaceutical dosage form. Study Design: Place and Duration of the Study: RBVRR women's college of pharmacy, Barkatpura, Hyderabad, between june 2019 and july 2020. Methodology: The RP-HPLC method was developed on Sunsil C18 150 mm x 4.6mm x 5µ column using acetonitrile : water (pH maintained at 3.5 with acetic acid) [70:30] as mobile phase at flow rate 0.8 ml/min and UV detection at 250 nm. Results: Tigecycline exhibited linearity over the concentration range of 5-40 µg/mL (R2 > 0.999). The analytical method showed good precision with % RSD below 2. The method showed suitable accuracy and robustness. Conclusion: Validation of the developed method was done as per International Conference on Harmonization (ICH) Q2R1 guidelines.

Extensively drug-resistant Acinetobacter baumannii (XDRAB) pulmonary infection is a serious respiratory system infection. Patients are often very sick and even need to be admitted to the ICU for treatment. In this case report, we presented our treatment experience of one XDRAB pulmonary infection patient. A 71-year-old male patient was admitted to our hospital complaining of "fatigue accompanied by fever for 2 days and shortness of breath for 1 day". The patient's admission diagnosis was as follows: severe pneumonia, acute respiratory distress syndrome, I type respiratory failure, septic shock, cardiac insufficiency, liver insufficiency, and hypertension. Imipenem/cilastatin sodium combined with moxifloxacin were first applied. Then, tigecycline, imipenem/cilastatin and caspofungin were used. The drug sensitivity results suggested that the XDRAB strain of this patient's sputum culture was sensitive to polymyxin only. Thus, colistin sulfate and cefoperazone/sulbactam were applied. The medication process of the patient was monitored. We found that a colistin sulfate intravenous injection combined with aerosol route combined with cefoperazone/sulbactam was effective in the treatment of XDRAB pulmonary infection, and no adverse drug reactions were observed during the treatment. The anti-infection therapy of intravenous colistin sulfate combined with nebulization and cefoperazone/sulbactam could be a good choice for the treatment of XDRAB lung infections.

Objective Donor-derived carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has recently emerged as a critical early complication after renal transplantation. Although CRKP is usually sensitive to tigecycline, monotherapy with this drug is often less than effective. We investigated the efficacy of a combined regimen of tigecycline with high-dose, extended-infusion meropenem in the treatment of donor-derived CRKP infection after kidney transplantation. Methods From Jan. 2016 to Dec. 2017, a total of 12 CRKP isolates were detected from cultures of the organ preservation solution used for soaking the donor kidneys at our institute. Probable or possible donor-derived infection (DDI) was identified in 8 transplant recipients. Clinical data were retrospectively analyzed. Results Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing CRKP was reported to be positive in organ preservation solution cultures at 3.5±0.9 days after transplantation, leading to surgical site (n=3), urinary tract (n=4), and/or bloodstream (n=2) infections in 8 recipients. The drug susceptibility tests showed that CRKP was sensitive to tigecycline, but resistant to meropenem. In 7 patients who received tigecycline combined with high-dose extended-infusion meropenem, DDIs were successfully cured. The length of hospital stay was 31 (18-129) days, and the serum creatinine at discharge was 105.8±16.7 µmol/L. The one remaining patient who received tigecycline combined with intravenous-drip meropenem died of septic shock. A median follow-up of 43 months (33-55) showed no recurrence of new CRKP infection in the 7 surviving recipients. Conclusion It was suggested that a prompt and appropriate combination therapy using tigecycline with high-dose extended-infusion meropenem is effective in treating donor-derived KPC-2-producing CRKP infection after renal transplantation.

Nancy G Banoub,1 Sarra E Saleh,2 Hala S Helal,1 Khaled M Aboshanab2 1Department of Microbiology and Immunology, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt; 2Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo, EgyptCorrespondence: Khaled M AboshanabDepartment of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, EgyptTel + 20-228429040; +20-1007582620Fax + 20-224051107Email aboshanab2012@pharma.asu.edu.egBackground: Successful treatment of Acinetobacter (A.) baumannii-associated infection is complicated by the emergence of multidrug resistance (MDR), particularly in clinical settings. This urges searching for new alternatives to encounter such health problem.Aim: This study aimed to evaluate certain antibiotic combinations and CNPs either alone or in combination of some selected antibiotics for the purpose of combating MDR A. baumannii clinical isolates.Methods: A total of 51 A. baumannii clinical isolates were recovered from discharged clinical specimens of the Clinical Microbiology Central Laboratory of AL Kasr Al Aini hospital, Cairo, Egypt. Conventional standard Lab tests were used for identification followed by recA gene testing for confirmation. Antimicrobial susceptibility tests were conducted out according to CLSI guidelines. Genotypic analysis using Enterobacterial Repetitive Intergenic Consensus-polymerase chain reaction (ERIC-PCR) of the respective isolates showed that they were clustered in nine clones. The prepared CNPs were characterized by dynamic light scattering and HR-transmission electron microscope imaging. Antibiotic combinations and co-effect of CNPs with some selected antibiotics (either each alone or in combination of two) were evaluated using the Checkerboard microdilution and minimum inhibitor concentration decrease factor (MDF) methods, respectively.Results: The recovered 51 A. baumannii clinical isolates were MDR (100%) of these 92% (47/51) were extensively drug resistance (XDR). Combinations of colistin (CT)+meropenem (MEM) and MEM+tigecycline (TGC) showed synergism in 77.7% and 44.4% and additive effects in 22.3% and 55.6% of the tested MDR A. baumannii isolates (n=51), respectively. However, CT+TGC combination showed antagonism. CNPs exhibited good inhibitory activity (inhibition zones ranged from 24 to 31 mm) against selected nine MDR A. baumannii isolates (one isolate from each clone). The MIC of CNPs at concentrations (ranging from 1 to 5 mg/mL) were from 0.16 to 0.25 mg/mL, indicating good in vitro antimicrobial activities. CNPs (5 mg/mL) when combined with CT, TGC or MEM, CT+MEM and TGC+MEM significantly increased the susceptibilities of the MDR A. baumannii isolates to these antibiotics by 88.8%, 66.6%, 100%, 77.7%, and 44.4%, respectively. No significant effects were observed when CNPs (5 mg/mL) were combined with CT+TGC.Conclusion: The current study demonstrated the significant in-vitro activities of CNPs either alone or in combination with CT, TGC or MEM, CT+MEM and TGC+MEM and the successful combinations of MEM either with CT or with TGC against the MDR A. baumannii pathogens. However, further in vivo studies should be conducted to verify such activities and their potential use in human.Keywords: A. baumannii, multidrug resistance, chitosan nanoparticles, antibiotic combinations, meropenem, colistin, tigecycline

Background: Staphylococcus aureus (SA) is a major etiological pathogen causing multiple infections and broadly known as a serious public health challenge faced due to antibiotic resistance. It is the need of time that infection prevention and control strategies; and antibiotic stewardship policies have to be employed conjointly to minimize the extended rise of antibiotic resistance. Objectives: To determine the frequency and sensitivity patterns of Staphylococcus aureus in tertiary care setting. Study Design: Descriptive study Place & Duration of Study: Pathology Laboratory of tertiary care center from 1st March’ 2020 till 28th February’ 2021. Materials & Methods: A total 643 Staph. aureus isolated from various clinical specimens received in a tertiary care hospital; were processed and identified by culture, staining and bench tests. Sensitivity testing was done by Disc Diffusion method. Resistance to cefoxitin(30µg) was labelled as Methicillin Resistant Staphylococcus aureus (MRSA). Constitutive and Inducible Clindamycin resistance was also evaluated. (CLSI, 2020-21). Results: During the study period 125 (19.44%) MRSA were recovered. Statistically, gender distribution regarding MRSA was significant, most of SA was recovered from blood (53.68%), while 46.31% from pus and wound swabs. The frequency of MRSA from Surgical and allied wards was higher (52.63%) than Medicine and allied wards (47.36%). Sensitivity to vancomycin, linezolid and tigecycline was noted 100% by all the isolates. Sensitivity to clindamycin and Doxycycline was 68.42% and 64.81% respectively; while resistance to erythromycin, ciprofloxacin and trimethoprim/sulfamethoxazole was 73.68%, 60% and 57.89%, respectively. Conclusion: The hazardous infections due to Staphylococcus aureus are worrisome in the present therapeutic scenario. A levelheaded prescription of sensitive antibiotics has to be ensured to minimize the rising frequency of resistant strains of SA.

Background: Misuse of antibiotics is the leading factor promoting emergence of bacterial resistance, a situation that has become a serious public health challenge. Among the leading bacteria that have developed resistance to antibiotics are Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, which have caused infections in patients, resulting in considerable mortality. The objective of this retrospective study was to assess antibiotic resistance rates of bacterial pathogens isolated from clinical specimens in two Lebanese hospitals between the years 2018 and 2019. Methodology: Bacteria isolated from routine clinical specimens collected from hospitalized patients in two hospitals, Haroun and Bekaa, in Lebanon for 2018 and 2019, were analyzed. Bacteria isolation and identification were carried out at the laboratory of each hospital using conventional microbiological methods. Antimicrobial susceptibility testings (AST) of each bacterial isolate to antibiotics were performed by the disc diffusion test and interpreted using EUCAST, CLSI or WHO/AST guidelines. Comparisons of the mean resistance rates of each isolate to individual antibiotics by year of isolation were done using the Z-test and p< 0.05 was considered statistically significant. Results: There were a total of 1698 bacteria isolates recovered from hospitalized patients in the two hospitals for 2018 and 2019, of which 87.5% were Gram-negative and 12.5% were Gram-positive bacteria. The most frequent among the Gram-negative isolates was E. coli (66.1%) followed by P. aeruginosa (13.3%), K. pneumoniae (7.7%), Proteus mirabilis (6.7%) and Enterobacter spp (6.3%), while coagulase positive staphylococci CoPS (68.4%) and E. faecalis (31.6%) were the two Gram positive isolates. Of the Gram-negative isolates over the two-year period, 72.2% of E. coli and 76.3% of K. pneumoniae were resistant to ceftazidime, 93% of P. mirabilis to colistin, and 98% of Enterobacter to cefoxitin, but low resistance rates were demonstrated by E. coli to imipenem (1%), K. pneumoniae to tigecycline and amikacin (0.9%), P. mirabilis to imipinem (2%), and Enterobacter to amikacin, ertapenem and tigecycline (3%). Resistance of P. aeruginosa varied between 2% to colistin and 24% to levofloxacin. For the Gram-positive bacteria, 79.1% of E. faecalis were resistant to erythromycin while 70% of CoPS were resistant to cefoxitin, but no isolate was resistant (0%) to linezolid, and only 1% to teicoplanin. Except for Enterobacter spp that showed significant increase in resistance rates (by 250%) to piperacillin/tazobactam in 2019 over 2018, resistance rates of other Gram-negative isolates significantly decreased in 2019 compared to 2018 (p

Wenjuan Yan,1,&ast; Qi Zhang,1,&ast; Yingjie Zhu,1 Nan Jing,1 Youhua Yuan,1 Yi Zhang,2 Siying Ren,3 Dongmei Hu,4 Wenmin Zhao,5 Xiaojuan Zhang,6 Caiqin Shi,7 Meiyun Wang,8 Yi Li1 1Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, People’s Republic of China; 2Department of Clinical Laboratory, Zhengzhou Central Hospital, Affiliated to Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Clinical Laboratory, Kaifeng People’s Hospital, Kaifeng, Henan, People’s Republic of China; 4Department of Clinical Laboratory, Zhumadian First People’s Hospital, Zhumadian, People’s Republic of China; 5Department of Clinical Laboratory, Kaifeng Central Hospital, Kaifeng, Henan, People’s Republic of China; 6Department of Clinical Laboratory, Gongyi People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 7Department of Microbiology Laboratory, KingMed Diagnostics, Zhengzhou, Henan, People’s Republic of China; 8Department of Medical Imaging, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi LiDepartment of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, People’s Republic of ChinaTel +86 159 39039006Email liyilabmed@henu.edu.cnPurpose: To evaluate polymyxin-resistant Klebsiella pneumoniae and Escherichia coli prevalence and characteristics in the Henan province, China.Materials and Methods: A total of 2301 bacterial isolates collected at six hospitals were assessed. Their response to polymyxin was evaluated by minimum inhibitory concentration (MIC) analysis, and the mobilized colistin resistance (mcr) and carbapenemase gene were explored. Mutations on mgrB, phoPQ, pmrAB, and crrAB in polymyxin-resistant K. pneumoniae were detected by PCR. phoP, phoQ, pmrK, pmrA, pmrB, and pmrC transcriptional levels were quantified by RT-qPCR. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing were performed to determine the phylogenetic relationship between the polymyxin-resistant isolates.Results: Of the E. coli and K. pneumoniae isolates identified, 0.3% and 1.4% were polymyxin-resistant, respectively, with MICs of 4– 64 μg/mL. All polymyxin-resistant isolates were susceptible to tigecycline. Four E. coli isolates were mcr-1-positive and one was carbapenem-resistant, carrying blaNDM-5 and mcr-1. One K. pneumoniae isolate was mcr-1-positive and nine were carbapenem-resistant (PRCRKP), carrying blaKPC-2 but not mcr-1. The five E. coli isolates belonged to four sequence types (ST2, ST132, ST632, and ST983). All PRCRKP isolates belonged to ST11. However, all 16 isolates belonged to different PFGE types with < 95% genetic similarity. Insertion sequences in mgrB were detected in nine (81.8%) polymyxin-resistant K. pneumoniae samples. Colistin resistance was linked with pmrHFIJKLM operon upregulation, with phoP, phoQ, and pmrK being overexpressed in all but one of the polymyxin-resistant K. pneumoniae samples. Furthermore, 33.3% of patients carrying polymyxin-resistant isolates had previously used polymyxin, and 66.7% patients displayed good clinical outcomes.Conclusion: The K. pneumoniae polymyxin resistance rate was slightly higher than that of E. coli and mcr-1 was more common in E. coli than in K. pneumoniae. Moreover, the insertion of ISkpn14 into mgrB may be the main contributor to polymyxin-resistance in K. pneumoniae in Henan.Keywords: polymyxin, Escherichia coli, Klebsiella pneumoniae, mcr, Henan province

Background Fatal hemorrhagic pneumonia is one of the most severe manifestations of Stenotrophomonas maltophilia (SM) infections. Here, we aimed to investigate the clinical characteristics of SM bacteremia and to identify the risk factors of hemorrhagic pneumonia caused by SM in patients with hematologic diseases. Methods The clinical records of 55 patients diagnosed with hematologic diseases and SM bacteremia were retrospectively reviewed. We compared patients’ clinical characteristics and outcomes between the hemorrhagic pneumonia group and non-hemorrhagic pneumonia group. Results Twenty-seven (49.1%) patients developed hemorrhagic pneumonia. The overall mortality rate of SM bacteremia was 67.3%. Hemorrhagic pneumonia (adjusted HR 2.316, 95% CI 1.140–4.705; P = 0.020) was an independent risk factor of 30-day mortality in hematological patients with SM bacteremia. Compared with the non-hemorrhagic pneumonia group, patients in the hemorrhagic pneumonia group were older and showed clinical manifestations as higher proportions of isolated SM in sputum culture, neutropenia and elevated procalcitonin (PCT). Multivariate analysis showed that neutropenia, high levels of PCT, prior tigecycline therapy within 1 month were independent risk factors associated with hemorrhagic pneumonia. Conclusions Neutropenia, high level of PCT and prior tigecycline therapy within 1 month were significant independent predictors of hemorrhagic pneumonia in hematologic patients with SM bacteremia. Due to no effective antibiotics to prevent hemorrhagic pneumonia, prophylaxis of SM infection and its progression to hemorrhagic pneumonia is particularly important.

Objective To explore the features and risk factors of bacterial skin infections (BSIs) in hospitalized patients with bullous pemphigoid (BP). Methods Records were retrospectively reviewed for 110 hospitalized patients with BP admitted to Peking University First Hospital between 2013 and 2019. Bacterial species and drug resistance were assessed, and then the underlying risk factors for BSIs were evaluated. Results Infections were present in 40% (44/110) of the patients. Staphylococcus aureus (72.7%, 32/44) was the most common bacterium, and it was highly resistant to penicillin (81.3%, 26/32), erythromycin (62.5%, 20/32), and clindamycin (56.3%, 18/32), but 100.0% sensitive to vancomycin and tigecycline. Coronary heart disease (P = .02; odds ratio [OR], 12.68), multisystem comorbidities (P = .02; OR, 3.67), hypoalbuminemia (P = .04; OR, 3.70), high levels of anti-BP180 antibodies (>112.4 U/mL; P = .003; OR, 6.43), and season (spring: reference; summer: P = .002; OR, 23.58; autumn: P = .02; OR, 12.19; winter: P = .02; OR, 13.19) were significantly associated with BSIs. Conclusions Hospitalized patients with BP had a high incidence of BSIs, and those patients with underlying risk factors require careful management to prevent and control BSIs.

Background: Of all enterococci species, the most renowned clinically as multidrug-resistant pathogens are Enterococcus faecium and Enterococcus faecalis. Vancomycin-resistant Enterococcus (VRE) species are the principal cause of opportunistic hospital-acquired infections, due to numerous resistance mechanisms. Methods: In this study, the prevalence and antibiotic resistance profiles of VRE according to clinical sources from three selected hospitals in Southwest-Nigeria were investigated. Altogether, 431 samples (urine, rectal, and wound swabs - caesarian section (CS), automobile accidents, and other skin lesions and abrasions) were collected from three selected hospitals in Osun State, Nigeria. Established techniques were employed for the recovery of enterococci and screening for VRE while antibiotic susceptibility tests were carried out by disc diffusion technique. Results: Altogether, 208 (48.3%) enterococci strains were recovered from which 85 (40.9%) were VRE. E. faecium predominated at 71.8% (61/85) and E. faecalis at 28.2% (24/85) as determined by phenotypic characterization. VRE isolates exhibited 100%, 97.6%, and 92.9% resistance to ampicillin, clindamycin, and quinupristin-dalfopristin (Q/D) respectively. The least resistance in-vitro was to tigecycline (27.1%). None of the antibiotics exhibited 100% activity against all the isolates. vanA resistant phenotype was prevalent at 65.9%. E. faecium from all study locations displayed higher levels of resistance than E. faecalis. Multiple antibiotic resistance (MAR) indices in all VRE isolates were ≥0.2, all being multidrug-resistant. Conclusions: The high prevalence rate along with the high level of multidrug resistance observed in the present study is worrisome and poses a continuous threat in the therapy of illnesses triggered by VRE as vancomycin was perceived as a drug of choice to curb enterococcal infections.

Shiga toxin-producing Escherichia coli (STEC) is an important foodborne pathogens, known to cause enteric infections especially diarrhea, mainly attributed to Shiga toxins (Stxs). The use of certain antibiotics for treating this infection is controversial, owing to an increased risk for producing Stxs (Stx 1 and Stx 2). Increased antibiotic resistance is also thought to be involved in the pathogenesis of STEC diseases. The purpose of this study was to analyze the effects of antibiotics on induction of Stx 1 and Stx 2 in clinical STEC isolates and to investigate the relationships between increased resistance and Stx production. Fifteen clinical isolates were treated with sub minimum inhibitory concentrations (Sub MIC) of clinically used antibiotics (ciprofloxacin, fosfomycin, tigecycline, and meropenem), and the changes in expression levels of stx1 and stx2 genes were estimated using qRT-PCR. The expressions of Shiga toxins were found to be increased up to 6.5- and eightfold under ciprofloxacin and tigecycline Sub MIC, respectively. Fosfomycin had weak induction effect of up to twofold, whereas meropenem had the weakest influence on such expression. Resistant isolates were found to be more prone to increased expression of toxins.

The transferability of bacterial resistance to tigecycline, the 'last-resort' antibiotic, is an emerging challenge of global health concern. The plasmid-borne tet(X) that encodes a flavin-dependent monooxygenase represents a new mechanism for tigecycline resistance. Natural source for an ongoing family of Tet(X) resistance determinants is poorly understood. Here, we report the discovery of 26 new variants [tet(X18) to tet(X44)] from the poultry pathogen Riemerella anatipestifer, which expands extensively the current Tet(X) family. R. anatipestifer appears as a natural reservoir for tet(X), of which the chromosome harbours varied copies of tet(X) progenitors. Despite that an inactive ancestor rarely occurs, the action and mechanism of Tet(X2/4)-P, a putative Tet(X) progenitor, was comprehensively characterized, giving an intermediate level of tigecycline resistance. The potential pattern of Tet(X) dissemination from ducks to other animals and humans was raised, in the viewpoint of ecological niches. Therefore, this finding defines a large pool of natural sources for Tet(X) tigecycline resistance, heightening the need of efficient approaches to manage the inter-species transmission of tet(X) resistance determinants.

Efficient monitoring of circulating purulent-septic infectious agents in a clinical setting and a study on antibiotic susceptibility of isolated strains of microorganisms allows identifying changes in the pathogen structure and trends in antibiotic resistance development, which helps to determine the tactics of antibacterial therapy and elaborate appropriate measures. The aim of the study. Retrospective analysis of the results of microbiological monitoring of purulent-septic infectious (PSI) agents in the Orthopedics and Traumatology Department (OTD) of the Zaporizhzhia Central Ambulance and Emergency Care Hospital over the period 2017–2020 to determine the main antibacterial drugs for empirical therapy. Materials and methods. We analyzed the bacteriological test results of 664 clinical material samples obtained from OTD patients using bacteriological examination statistical reporting and analytical data of the WHONET 5.6 software. Results. The main PSI pathogens in the OTD were from the ESKAPE group: E. coli, S. aureus, K. pneumoniae, A. baumannii, E. faecalis, P. aeruginosa and S. epidermidis, P. mirabilis, C. amycolatum. Isolates of E. faecalis were sensitive to vancomycin, linezolid, S. aureus – to linezolid, tigecycline, netilmicin, A. baumannii – to tigecycline. All P. aeruginosa strains were resistant to ticarcillin/clavulanate, cefepime, chloramphenicol, imipenem, meropenem, aztreonam, ciprofloxacin. E. coli and K. pneumoniae were resistant to ampicillin, ticarcillin/clavulanate, aztreonam, ceftriaxone, cefepime. The number of isolates sensitive to piperacillin/tazobactam, carbapenems, levofloxacin, gentamicin, amikacin, chloramphenicol ranged from 37 % to 65 %. Conclusions. E. coli, S. aureus, K. pneumoniae, A. baumannii, E. faecalis, P. aeruginosa, S. epidermidis, P. mirabilis, C. amycolatum play an important role in the structure of PSI pathogens in the Orthopedics and Traumatology Department of Zaporizhzhia Central Ambulance and Emergency Care Hospital. The antibiotics of choice as the antibacterial empirical therapy for enterococcal infections are vancomycin, linezolid, for staphylococcal infections – vancomycin, linezolid, tigecycline, netilmicin. PSI pathogens continually evolve developing antibiotic resistance, and it is of particular importance to monitor antibiotic susceptibility of microorganisms within the OTD.