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Objective: To assess whether procalcitonin (PCT) levels can be a reliable indicator of when it is unnecessary to step up antibiotics in children with cancer and fever without source (FWS). Material and Methods: The medical records of children with hematologic-oncologic malignancies aged 3 months-15 years who had FWS ≥4 days and were admitted to Songklanagarind Hospital from December 2016 to February 2019 were reviewed. Results: FWS was identified in 89 patients. PCT levels were tested in 43 patients; 21 and 22 patients had low PCT (PCT

Background: Antimicrobial resistance in cystic fibrosis (CF) Pseudomonas aeruginosa airway infection is complex and often attributed to chromosomal mutations. How these mutations emerge in specific strains or whether particular gene mutations are clinically informative is unclear. This study focused on oprD, which encodes an outer membrane porin associated with carbapenem resistance when it is downregulated or inactivated. Aim: Determine how mutations in oprD emerge in two prevalent Australian shared CF strains of P. aeruginosa and their clinical relevance. Methods: The two most common shared CF strains in Queensland were investigated using whole genome sequencing and their oprD sequences and antimicrobial resistance phenotypes were established. P. aeruginosa mutants with the most common oprD variants were constructed and characterised. Clinical variables were compared between people with or without evidence of infection with strains harbouring these variants. Results: Frequently found nonsense mutations arising from a 1-base pair substitution in oprD evolved independently in three sub-lineages, and are likely major contributors to the reduced carbapenem susceptibility observed in the clinical isolates. Lower baseline FEV %predicted was identified as a risk factor for infection with a sub-lineage (odds ratio=0.97; 95% confidence interval 0.96-0.99; p

Background: There are no reports on the effects of interventions, such as discontinuation and change and/or deescalation of carbapenems and anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotics by an antimicrobial stewardship team focusing on detailed patient outcomes. This study aimed to evaluate these effects. Methods: This retrospective cohort study was conducted at a tertiary care hospital from December 2018 to November 2019. Results: Favorable clinical responses were obtained in 165 of 184 cases (89.7%) in the intervention-accepted group, higher than those in the not accepted group (14/19 cases, 73.7%; P = .056). All-cause 30 day mortality was lower in the accepted group than in the not accepted group (1.1% and 10.5%, respectively; P = .045). The microbiological outcomes were similar between the two groups. Duration of carbapenem and anti-MRSA antibiotic use in the accepted group was significantly lower than that in the not accepted group (median [interquartile range]: 8 days [5-13] versus 14 days [8-15], respectively, P = .026 for carbapenem; 10 days [5.3-15] vs 15.5 days [13.8-45.3], respectively, P = .014 for anti-MRSA antibiotic). Conclusions: This is the first study to investigate the effects of interventions such as discontinuation and change and/ or de-escalation of antibiotics on detailed outcomes. Our intervention could reduce the duration of carbapenem and anti-MRSA antibiotic use without worsening clinical and microbiological outcomes. (c) 2021 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Background: Pseudomonas aeruginosa ( P. aeruginosa ) is a gram negative bacteria that is known to cause nosocomial infections. Carbapenem is used to treat the damage caused by P. aeruginosa , however it is becoming resistant to carbapenems because of the production of β-lactamases. The objectives of the study were to systematically review the prevalence of bla NDM-1 in carbapenem-resistant Pseudomonas aeruginosa (CRPA) and to review and analyze the clinical sources as well as the antibiotic resistance profile of CRPA carrying bla NDM-1 . Methods: The researchers systematically searched PubMed, ScienceDirect, and Google Scholar. Studies that met the inclusion criteria were included in the review. In assessing the methodological quality of the included studies, the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data and the JBI Critical Appraisal Checklist for Case Reports were used. Results: A total of nine studies were included in which eight were cross-sectional studies and one was a case report. The highest prevalence rate reported was 54.55% in bla NDM-1 positive CRPA isolates among the cross-sectional studies. The three most frequent sources of clinical isolates of CRPA carrying bla NDM-1 include urine, wound discharge, and tissue, among the included studies. Lastly, this review showed that among the included studies, CRPA isolates carrying bla NDM-1 were most resistant to ceftazidime and gentamicin. Conclusions: There is varying prevalence of bla NDM-1 in CRPA in different countries. Urine, wound discharge, and tissue specimens being the most frequent sources of CRPA isolates carrying bla NDM-1 poses a challenge that must be given attention by the infection control committee, thus the need for proper handling and processing of clinical specimens. Resistance to ceftazidime and gentamicin among the CRPA isolates carrying bla NDM-1 highlights the growing challenge of successfully treating infections caused by this bacteria. This challenge reminds us of the importance and purpose of antibiotic stewardship that emphasizes the improvement of proper antibiotic prescription by the physicians and proper antibiotic use by the patients that can help in preventing harm and antibiotic resistance. Doi: 10.28991/SciMedJ-2021-0304-9 Full Text: PDF

Objectives: To determine frequency of multidrug resistant (MDR) and extensive drug resistant (XDR) strains of Salmonella typhi (S. typhi) and Salmonella paratyphi (S. paratyphi) in Quetta, Balochistan of Pakistan Study Design: Descriptive Cross-Sectional Place and Duration: Department of Microbiology, CMH Quetta, Pakistan. from March 2019 to March 2020 Materials and Methods: A total of 2760 (n) suspected cases of typhoid fever, irrespective of age and gender, reporting at the hospital in this duration and underwent blood culture. Isolates were cultured and identified using standard microbiological procedures. Antimicrobial sensitivity against typhoidal Salmonellae was determined using Kirby-Bauer disc diffusion method as per the guidelines of Clinical and Laboratory Standards Institute (2018) and all the XDR isolates were confirmed by Vitek 2 system. Results: A total of 173 (6.3%) cultures showed positive results. with mean age of 18.9 ± 11.1 years, out of which 136 (78.6%) were male and 37 (21.1%) were female patients. Antibiotic susceptibility results showed that 166 (96%) of isolates were S. typhi. MDR strains were observed in 104(60.1%) and XDR strains were observed in 81 (46.8%) cases. Conclusion: A significant proportion of S. typhi isolates from confirmed cases of enteric fever demonstrated MDR (60.1%) and XDR (46.8%) strains in Quetta, Balochistan. We recommend empiric therapy with azithromycin in patients with uncomplicated and therapy with carbapenem for complicated cases of enteric fever acquired in Karachi or Quetta. Large scale population-based studies are recommended to get better information about antibiotic susceptibility pattern of S. typhi and S. paratyphi in other areas.

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.

BackgroundKlebsiella pneumoniae is a critically important pathogen in the Philippines. Isolates are commonly resistant to at least two classes of antibiotics, yet mechanisms and spread of its resistance are not well studied.MethodsA retrospective sequencing survey was performed on carbapenem-, extended spectrum beta-lactam- and cephalosporin-resistant Klebsiella pneumoniae isolated at 20 antimicrobial resistance (AMR) surveillance sentinel sites from 2015-2017. We characterized 259 isolates using biochemical methods, antimicrobial susceptibility testing, and whole genome sequencing (WGS). Known AMR mechanisms were identified. Potential outbreaks were investigated by detecting clusters from epidemiologic, phenotypic and genome-derived data.ResultsPrevalent AMR mechanisms detected include blaCTX-M-15 (76.8%) and blaNDM-1 (37.5%). An epidemic IncFII(Yp) plasmid carrying blaNDM-1 was also detected in 46 isolates from 6 sentinel sites and 14 different sequence types (ST). This plasmid was also identified as the main vehicle of carbapenem resistance in 2 previously unrecognized local outbreaks of ST348 and ST283 at 2 different sentinel sites. A third local outbreak of ST397 was also identified but without the IncFII(Yp) plasmid. Isolates in each outbreak site showed identical STs, K- and O-loci, and similar resistance profiles and AMR genes. All outbreak isolates were collected from blood of children aged ConclusionWGS provided an in-depth understanding of the epidemiology of AMR in the Philippines, which was not possible with only phenotypic and epidemiologic data. The identification of three previously unrecognized Klebsiella outbreaks highlights the utility of WGS in outbreak detection, as well as its importance in public health and in implementing infection control programs.summaryWhole genome sequencing identified three distinct previously unrecognized local outbreaks in a retrospective study in the Philippines, along with an epidemic plasmid carrying antimicrobial resistance genes, highlighting its importance in antimicrobial resistance surveillance, outbreak detection and infection control.

BACKGROUND Prospective audit and feedback is a method that allows the antimicrobial stewardship program (ASP) team to interact with attending physicians to tailor antibiotic therapy, including de-escalation, as appropriate. This study aimed to evaluate the acceptance and outcomes of ASP de-escalation recommendations in children who received meropenem. METHODS A prospective cohort study was conducted in children aged 1 month to 18 years who received meropenem in a tertiary-care teaching hospital. The ASP team gave recommendation between 72 and 120 h after initiating meropenem therapy. Acceptance of de-escalation recommendations among primary physicians was evaluated within 24 h of recommendation. Outcomes included clinical success rate on the 7th day and incidence rate of acquisition of carbapenem-resistant gram-negative bacteria (CR-GNB) within 30 days. RESULTS From March to December 2019, 217 children with a median (interquartile range) age of 2.1 (0.6, 9.5) years received meropenem. The ASP team gave recommendations in 127 (58.5%) of cases for continuation of meropenem therapy and 90 (41.5%) of cases for de-escalation. The overall acceptance of ASP de-escalation recommendations was 57.8% (95%CI: 46.9-68.1%). Clinical success rates were 85.2% in the accepted group compared to 77.5% in the rejected group (P = 0.06). The incidence rate of acquisition of CR-GNB within 30 days after treatment was 5.8% in the accepted group and 15.8% in the rejected group (P = 0.03). CONCLUSIONS About half of the recommendations to de-escalate meropenem prescriptions were accepted through the ASP intervention. Carbapenem-resistant gram-negative bacteria acquisitions was less likely in the de-escalation group. A robust de-escalation strategy 72 h following carbapenem initiation should be encouraged to combat multidrug-resistant organisms.

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

Purpuse The carbapenem-resistant Bacteroides fragilis group (CR-BFG) bacteria have been reported in several countries recently with increasing global attention. The high incidence of CR-BFG isolated from our hospitalized patients has become an important problem. Therefore, we aimed to determine the frequency and associated factors for intestinal colonization by carbapenem-non-susceptible BFG (CNS-BFG) among adult patients hospitalized at intensive care units, neurosurgery and internal medicine wards in our hospital. Methods Rectal swabs (n = 1200), collected from 766 patients between February 2014 and March 2015, were inoculated onto kanamycin-vancomycin-leaked blood agar containing 0.125 mg/L meropenem. The isolates were identified by MALDI-TOF MS. Susceptibility testing was performed by agar dilution method. The carbapenemase gene (cfiA) was detected by PCR. Logistic regression analysis was used to evaluate the associated factors for intestinal colonization by CNS-BFG. Results A total 180 non-duplicate BFG isolates were obtained from 164 patients. Ten different species, including Parabacteroides distasonis (n = 46, 25.6%), and Bacteroides fragilis (n = 30; 16.6%), were identified. Twenty-five percent of the isolates were non-susceptible to meropenem (MIC >2 mg/L). The highest prevalence of meropenem resistant strains (MIC >8 mg/L) was detected among B. fragilis (n = 12), followed by Parabacteroides spp. (n = 4). All but one B. fragilis strains were cfiA gene positive. Hospital admission, increasing Charlson score, use of antibiotics; including carbapenems in past three months, colonization with other accompanying carbapenem-resistant Gram negative bacteria (Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa), and having undergone surgical operations were significantly associated with RCS- BFG colonization. Conclusions The high carriage rate of CNS-BFG in hospitalized patients may lead to worse clinical outcomes, such as serious infections and mortality, and deserves attention.

Beta-lactam antibiotic resistance can occur in ESBL-producing bacteria such as E.coli and K.pneumoniae, which can cause UTI. One of the risk factors for infection is the non-intensive care space density level. The objective of this study was to determine the sensitivity pattern of ESBL-producing bacteria in urine specimens of patients in the non-intensive care of Ulin General Hospital, Banjarmasin, in the period of 2016-2018. A descriptive study with a cross-sectional design using data results of urine culture and antibiotic susceptibility patterns data in non-intensive care patients at Ulin General Hospital from 2016 to 2018. The urine test results showed 96 positive isolates of ESBL-producing bacteria, consisting of ESBL-E.coli (69.8%) and ESBL-K.pneumonia (30.2%). Antibiotics with low sensitivity tests were Penicillin, Cephalosporin, Monobactam, and Penicillin/beta-lactam inhibitor combinations. Contrastingly, antibiotics with high sensitivity were Aminoglycoside, Carbapenem, and Glycylcycline. It was concluded from this study that the ESBL-producing bacteria in urine specimens for non-intensive care patients of Banjarmasin Ulin General Hospital in the period of 2016-2018 showed varying sensitivity to antibiotics

Extended-Spectrum Beta-Lactamase (ESBL) producing bacteria is a type of resistance that leads to complex management of patients in intensive care due to their resistance to first, second, and third-generation Cephalosporin and monobactam antibiotics. The most ESBL-producing bacteria are found in the family Enterobacteriaceae, especially Klebsiella pneumoniae and Escherichia coli. The purpose of this research was to determine the sensitivity pattern of ESBLproducing bacteria in Intensive Care Units (ICUs) of Ulin Hospital, Banjarmasin, in the period of 2016-2018. This research was a descriptive study with a cross-sectional approach using data from the laboratory medical records of patients with positive ESBL in the ICUs of Ulin Hospital, Banjarmasin, between 2016 and 2018. The research sample was taken by the total sampling method. This research obtained 216 isolates of ESBL-producing bacteria consisting of 155 (71.8%) isolates of Klebsiella pneumoniae and 61 (28.2%) Escherichia coli. It was found that the Cephalosporin antibiotics (Cefazolin, Ceftazidime, Ceftriaxone, and Cefepime) and monobactam antibiotic (Aztreonam) had the lowest sensitivity. Aminoglycoside antibiotics (Amikacin), Carbapenem (Ertapenem and Meropenem), and Tetracycline (Tigesycline) were the most sensitive antibiotics. It was concluded that both Klebsiella pneumoniae and Escherichia coli were the most dominant ESBL-producing bacteria and showed good sensitivity to the Amikacin, Ertapenem, Meropenem, and Tigecycline.

Meropenem is a new Carbapenem antibacterial agent with wide spectrum of activity for intravenous administration. It is synthetic derivative of Thienamycin. Three analogues of Meropenem are evaluated and active against 18 bacterial strains. Meropenem causes rapid bacterial cell death by covalently binding to penicillin binding proteins (PBS). Structural modification at C-2 position, produced double promoiety prodrug of Meropenem and increases bioavailability of oral administration. Other forms of drug such as liposome and nanoparticles are also available with enhanced absorption. 14C labelled Meropenem prepared from 14C Dimethylamine hydrochloride is used for the analysis of M. tuberculosis transpeptidase. ICI213,689 is the only metabolite of Meropenem and it is inactive. Meropenem penetrates well into the body fluids and tissues including cerebrospinal fluid. Its bioavailability is 100% on intravenous administration. Hence it is used in the treatment of meningitis, febrile neutropenia, anthrax and various other skin and skin structure infections. Dosage reduction is required in patient with reduced renal function but not in hepatic impairment. Seizures, gastrointestinal haemorrhage are observed in patients. Vabmoere is the combination of Meropenem and Vaborbactam which is active against the Carbapenem resistant Enterobacteriacea. Meropenem is an effective broad-spectrum antibacterial drug for the treatment of wide range of infection including polymicrobial infection in both children and adult.

Introduction: Antimicrobial-resistant Acinetobacter species are implicated in a variety of infections including nosocomial bacteraemia, secondary meningitis, and urinary tract infections. Carbapenem including meropenem-resistant Acinetobacter is recognized as one of the most difficult antimicrobial resistant gram-negative bacilli to control and treat. It was classified as an urgent threat by Centers for Disease Control and Prevention in 2019 Antibiotic Resistance Threats Report. This study was carriedout to determine the prevalence of meropenem resistance among acinetobacter positive clinical samples in a tertiary care centre. Methods: A descriptive cross-sectional study was carried out in microbiology department of Clinical Laboratory Services among Acinetobacter positive clinical samples of a tertiary care center in Nepal. The culture and sensitivity reports of various clinical samples from April 2018 to April 2020 which were positive for Acinetobacter species were taken from hospital records section. Convenience sampling was done. Meropenem-resistant Acinetobacter samples were studied. Ethical approval was received from Institutional Review Committee (Ref No. 076/77/40). Analysis of data was done using Statistical Package for the Social Sciences version 26. Point estimate at 95% Confidence Interval calculated with ferquency. Results: Out of 121 Acinetobacter isolates, prevalence of meropenem-resistant Acinetobacter was reported in 93 (76.9%) at 95% Confidence Interval (69.39-84.40). Among the meropenem-resistant Acinetobacter samples, most of the samples were collected from the sputum 70 (75.2%) followed by blood 8 (8.6%). Conclusions: High prevalence of meropenem-resistant Acinetobacter species in our hospital setting is alarming. In addition, there is emergence of resistance against even the last resort drugs which is creating a treatment crisis.

Hye Jin Shi, Jae Hee Wee, Joong Sik Eom Division of Infectious Diseases, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, KoreaCorrespondence: Joong Sik EomDivision of Infectious Diseases, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, (21565) 774 Beon-gil 21, Namdongdae-ro, Namdong-gu, Incheon, KoreaTel +82-32-460-2630Fax +82-32-460-2631Email helppl@gachon.ac.krBackground: Urinary tract infections (UTIs) caused by extended spectrum beta-lactamase (ESBL) producing pathogens have increased and are treated with carbapenem in general. Carbapenem use is associated with prolonged hospitalization or daily outpatient visit. The aim of this study was to investigate patients with UTIs by ESBL-producing pathogens for early discharge using an old oral antibiotic, trimethoprim-sulfamethoxazole (TMP-SMX), which is susceptible to ESBL-producing pathogens.Methods: Data on UTIs caused by ESBL-producing pathogens from a single tertiary hospital were collected retrospectively. Patients who had been treated with intravenous carbapenems or oral TMP/SMX were included. Patients’ clinical and microbiological outcomes were compared between oral TMP/SMX and ertapenem treatment groups.Results: A total of 103 patients were included, 21 of whom had been treated with TMP/SMX, whereas 82 with ertapenem. Clinical outcomes between the two groups were not significantly different (TMP/SMX: 90.5%; ertapenem: 84.1%, p = 0.73). The microbiological cure rate was higher in the TMP/SMX group than in the ertapenem group (90.5% vs 58.5%, respectively, p = 0.01). The mean duration of hospitalization was significantly shorter in the TMP/SMX group than in the ertapenem group (8.00 ± 10.50 days vs 14.00 ± 37.00 days, p = 0.07). The mean duration of antibiotic treatment was longer in the ertapenem group than in the TMP/SMX group (16.45 ± 4.77 vs 12.76 ± 5.37 days, p = 0.006).Conclusion: For susceptible pathogens, TMP/SMX may enable early discharge as an effective oral antibiotic treatment option for UTIs caused by ESBL-positive pathogens. Additionally, use of oral antibiotics can shorten hospital stays and reduce medical costs.Keywords: oral antibiotics, ESBL, UTI, TMP/SMX, outpatient treatment

BackgroundAntimicrobial therapy is essential for the treatment of enteric fever, the infection caused by Salmonella serovars Typhi and Paratyphi A. However, an increase in resistance to key antimicrobials and the emergence of MDR and XDR in Salmonella Typhi poses a major threat for efficacious outpatient treatments.ObjectivesWe recently identified tebipenem, an oral carbapenem licensed for use for respiratory tract infections in Japan, as a potential alternative treatment for MDR/XDR Shigella spp. Here, we aimed to test the in vitro antibacterial efficacy of this drug against MDR and XDR typhoidal Salmonella.MethodsWe determined the in vitro activity of tebipenem in time–kill assays against a collection of non-XDR and XDR Salmonella Typhi and Salmonella Paratyphi A (non-XDR) isolated in Nepal and Bangladesh. We also tested the efficacy of tebipenem in combination with other antimicrobials.ResultsWe found that both XDR and non-XDR Salmonella Typhi and Salmonella Paratyphi A are susceptible to tebipenem, exhibiting low MICs, and were killed within 8–24 h at 2–4×MIC. Additionally, tebipenem demonstrated synergy with two other antimicrobials and could efficiently induce bacterial killing.ConclusionsSalmonella Paratyphi A and XDR Salmonella Typhi display in vitro susceptibility to the oral carbapenem tebipenem, while synergistic activity with other antimicrobials may limit the emergence of resistance. The broad-spectrum activity of this drug against MDR/XDR organisms renders tebipenem a good candidate for clinical trials.

Objectives: Both Enterobacter cloacae and Klebsiella pneumoniae have been regarded as important opportunistic pathogens for humans. Recent data have described the spread of multi-resistant strains of these organisms. Development of novel resistance phenotypes may result in a reduction in anti-infective efficacy, therefore making patient treatment decisions challenging. The Surveillance of Wisconsin Organisms for Trends in Antimicrobial Resistance and Epidemiology (SWOTARE) program aims to combat this issue and improve antibiotic stewardship by monitoring antimicrobial resistance at a local level.Design: Multi-center laboratory surveillance, with testing at a single location utilizing standardized media and susceptibility testing protocolsMethods: In the years 2018 and 2019, a total of 591 clinically-significant E. cloacae and 668 clinically-significant K. pneumoniae isolates were collected through this initiative; limited demographic data were also supplied. Isolates were tested by broth microdilution procedures advocated by Clinical and Laboratory Standards Institute.Results: On a statewide level, both E. cloacae and K. pneumoniae demonstrated in vitro potency to carbapenem and aminoglycoside agents at rates exceeding 96%. K. pneumoniae isolates were generally more susceptible to cephem and monobactam agents than E. cloacae isolates; the converse was true for fluoroquinolone agents. Patterns of local antimicrobial resistance were revealed that were not apparent at the state level. E. cloacae isolates submitted from the Northcentral and Southeast regions demonstrated decreased susceptibility to five antimicrobial agents (notably third- and fourth-generation cephems) when compared to the state average. Isolates derived from males, older individuals, and urogenital sources exhibited decreased susceptibility to third- and fourth-generation cephem agents (P ≤ 0.047). With respect to K. pneumoniae, antimicrobial resistance phenotype was not a function of geography or gender. However, isolates emanating from older patients and the respiratory tract showed decreased susceptibility to ampicillin/sulbactam and cefazolin, respectively (P ≤ 0.019).Conclusions: Antimicrobial resistance surveillance at a local level provides utility to community/rural hospital clinicians, pharmacists, and infection control practitioners. With respect to E. cloacae, further surveillance efforts may be necessary in the Northcentral and Southeast regions of Wisconsin. Subanalysis of demographic data indicated cephem-resistance correlates that are not apparent at the statewide level.

Background The prevalence of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) in the community has increased worldwide due to multifactorial reasons. ESBL-EC bloodstream infection (BSI) complicates the decision for proper antimicrobial administration. In this multicenter study, we investigated the prevalence, risk factors, and molecular background of community-onset (CO) ESBL-EC BSI. Methods We included data for all episodes of ESBL-EC BSI of community origin from May 2016 to April 2017 obtained from the Korean national antimicrobial resistance surveillance system, which comprises six sentinel hospitals. Data, including previous history of admission and use of antimicrobials and medical devices before BSI, were collected, along with microbiological analysis results. Results Among 1,189 patients with CO BSI caused by E. coli, 316 (27%) were identified as ESBL producers. History of admission, especially to a long-term care hospital (LTCH), and previous use of β-lactams/β-lactamase inhibitors, carbapenem, lincosamide, aminoglycoside, and extended-spectrum cephalosporin were independent risk factors for CO ESBL-EC BSI; admission to an LTCH showed the highest odds ratio (3.8, 95% confidence interval 2.3-6.1). The most common genotype was CTX-M-15 (N=131, 41%), followed by CTX-M-14 (N=86, 27%). ST131 was the most common sequence type among ESBL-EC groups (57%). Conclusions In Korea, 27% of CO E. coli BSI were caused by ESBL producers. From perspectives of empirical treatment and infection control, history of admission to an LTCH and antimicrobial use should be noted.

Infections with multidrug-resistant organisms among patients in intensive care units (ICUs) are associated with high mortality. Among multidrug-resistant organisms, carbapenem-resistant Enterobacterales (CRE) harbor important pathogens for healthcare-associated infections, including pneumonia, bacteremia, and urinary tract infections. Risk factors for CRE colonization include underlying comorbid conditions, prior antibiotics exposure, prior use of healthcare facilities, device use, and longer ICU stay. The mortality rate due to invasive CRE infection is 22%–49%, and CRE colonization is associated with an approximately 10-fold increased risk of CRE infection. Infection control measures include hand hygiene, contact precautions, minimizing the use of devices, and environmental control. Additionally, implementing active surveillance of CRE carriage should be considered in ICU settings.

During the past years, the emergence of multi-drug resistance Gram-negative bacilli (MDR-GNB), including the carbapenem resistant Klebsiella pneumoniae (CRKP) has increased leading to a significant threat to public health care. Recent advanced molecular methods have improved our knowledge on how antimicrobial resistance mechanisms develop and transferred among bacterial strains. The MDR pathogens, particularly CRKP, utilize various mechanisms of resistance such as antimicrobial agent degradation, modification of antimicrobial target and alteration of cell membrane permeability. Here, the emergence of CRKP and the major antibiotic resistance mechanisms employed by CRKP will be reviewed and described. Understanding such mechanisms can be essential to develop new antimicrobial drug and help with individual treatment decisions to use alternative options to carbapenem and β-lactam antibiotics.

Background: The noteworthy spread of carbapenem-resistant K. pneumoniae (CR-KP) isolates represents a significant safety threat. Objective: Determination of the carbapenemase genes incidence among CR-KP clinical isolates in Kafrelsheikh, Egypt. Methods: A total of 230 K. pneumoniae isolates were recovered from four hospitals in Kafrelsheikh, Egypt. Susceptibility testing was conducted using Kirby-Bauer method and automated-Vitek2 system. CR-KP isolates were tested using modified Hodge test (MHT) and combined disk synergy test. PCR and DNA sequencing were conducted for CR-KP isolates to rec- ognize the included carbapenemase-genes. Results: Out of 230 K. pneumoniae isolates, 50 isolates presented resistance to carbapenem (meropenem). All 50 CR-KP iso- lates were multidrug-resistant (MDR). Genes like blaNDM-1 and blaOXA-48 were the only detected genes among CR-KP with an incidence of 70.0% and 52.0%, respectively. Up to 74.0% of the tested isolates carried at least one of the two record- ed genes, among them 48.0% co-harbored both blaNDM-1 and blaOXA-48 genes. The accession-numbers of sequenced blaNDM-1 and blaOXA-48 genes were MG594615 and MG594616, respectively. Conclusion: This study reported a high incidence of MDR profile with the emergence of blaNDM-1 and blaOXA-48 genes co-existence in CR-KP isolates in Kafrelsheikh, Egypt. Hence, more restrictions should be applied against the spread of such serious pathogens. Keywords: Klebsiella pneumoniae; Egypt; carbapenem resistance; MDR; PCR; blaNDM-1; blaOXA-48; sequencing.

BACKGROUND: This study aimed to investigate the distribution pattern of carbapenemases and evaluate their solitary contribution to carbapenem resistance. METHODS: One hundred and twelve isolates of Acinetobacter baumannii (A. baumannii) isolated from the intensive care unit (ICU) of a southern China tertiary hospital were identified, and antimicrobial susceptibility tests (ASTs) of these strains were determined. Common carbapenemases were detected and the distribution pattern of carbapenemases was analyzed. Logistic regression and general linear model analyzed were performed to identify the correlation between antimicrobial susceptibility and carbapenemase genes. RESULTS: These 112 strains were classified into a carbapenem-resistant A. baumannii (CRAB) group (71.7%) and a carbapenem-susceptible A. baumannii (CSAB) group (28.3%). Carbapenemase genes, including blaOXA-51-like (100.0%), blaOXA-23 (93.4%), ISAba1/blaOXA-51-like (27.5%), blaNDM-1 (8.8%), blaOXA-24 (2.2%) and blaOXA-58 (2.2%) were detected in CRAB strains, and no blaSIM, blaVIM and blaIMP gene in these 112 isolates. There was a statistically significant difference between CSAB and CRAB group in carrying blaOXA-23 (P

Purpose To evaluate a low-cost multimodal intervention on the acquisition of carbapenem-non-susceptible Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa by patients in low-resource intensive care units. Materials and methods We performed a quasi-experimental study in a referral hospital in Jakarta, Indonesia: pre-intervention phase 1 (2013–2014), intervention phase 2 (2014–2015) and post-intervention phase 3 (2015–2016). The intervention was hand hygiene promotion and environmental cleaning and disinfection combined with patient disinfection and cohorting. The primary outcome was acquisition of resistant bacteria per 100 patient-days at risk, which was assessed by active microbiological surveillance and analysed with a multilevel Poisson segmented regression model. Results In phase 1 (387 patients), the acquisition rate was 4.3/100 days for carbapenem-non-susceptible A. baumannii versus 1.1/100 days for both K. pneumoniae and P. aeruginosa. There was a significant step change from phase 1 to phase 3 (361 patients) in the acquisition of carbapenem-non-susceptible strains, the incidence rate ratio (IRR) was 0.343 (99%CI: 0.164–0.717). This significant change was mainly due to reduced acquisitions of resistant A. baumannii (IRR 0.4, 99%CI: 0.181–1.061). Negative confounding was observed. Conclusion A multimodal intervention to prevent acquisition of resistant pathogens is feasible and may be effective in ICUs in lower-middle income countries.

Lewei Xie,1 Yaling Du,1 Xuemei Wang,1 Xinping Zhang,1 Chenxi Liu,1 Junjie Liu,2 Xi Peng,3 Xinhong Guo3 1School of Medicine and Health Management, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2School of Statistics and Mathematics, Central University of Finance and Economics, Beijing, People’s Republic of China; 3First Affiliated Hospital, School of Medicine, Shihezi University, Xinjiang, Shihezi, People’s Republic of ChinaCorrespondence: Xinping Zhang; Yaling DuSchool of Medicine and Health Management, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaTel +86 133 4995 0095; +86 180 0993 8932Email xpzhang602@hust.edu.cn; xpzhang602@163.com; 1147844190@qq.comPurpose: Carbapenem resistance due to the overuse of carbapenems has become a public health problem worldwide, particularly in low- and middle-income countries (LMICs). However, there are few policies guiding carbapenem prescription, and their effectiveness is still unclear. A regulation targeting carbapenem prescription was implemented in March 2017 in China. This study aimed to assess the effects of the regulation for providing evidence on the prudent use of carbapenems.Patients and Methods: This was an interventional, retrospective study started in January 2017. The intervention covered establishing performance appraisal indicators, special authorisation, strict prescribing restrictions, and dedicated supervision, particularly in the intensive care unit (ICU). Data on adult inpatients who received at least one carbapenems were extracted from January 2016 to December 2018. Segmented regression analysis was performed to evaluate the effect of the regulation.Results: A total of 2005 inpatients received carbapenems. Segmented regression models showed an immediate decline in the intensity of antibiotic consumption (IAC) of carbapenems (coefficient = − 9.65, p < 0.001), particularly imipenem (coefficient = − 6.82, p = 0.002), and the antibiotic consumption of carbapenems (coefficient = − 133.60, p = 0.003) in the ICU. And there is a decreasing trend in the IAC of meropenem (coefficient = − 0.03, p = 0.008) in all departments. Furthermore, the IAC of carbapenems and imipenem (coefficient = − 0.36, p = 0.035; coefficient = − 0.49, p = 0.025, respectively), and the average length of stay (ALoS) (coefficient = − 0.73, p < 0.001) showed downward trends in the ICU.Conclusion: The intervention effectively reduced the IAC of carbapenems and imipenem, carbapenem consumption and the ALoS in the ICU, and the IAC of meropenem in all departments. The effects of the intervention were significant in the ICU, which indicated an urgent need for stronger regulations focusing on critical departments in the future.Keywords: carbapenem prescription, ICU, multifaceted intervention, antimicrobial stewardship, effects assessment, segmented regression

Xiao Xu,&ast; Caifang Xu,&ast; Rabiu Bilya Salisu, Wei Xu Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei XuDepartment of Pediatrics, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, People’s Republic of ChinaEmail tomxu.123@163.comPurpose: Acinetobacter baumannii is a major cause of hospital-acquired infections. Studies showed that carbapenem resistance was related to mortality. Carbapenem resistance depends on expression of β-lactamase in adults. The present study explores the relationship between β-lactamase gene expression and carbapenem resistance and outcomes in children with A. baumannii infections.Patients and Methods: We gathered clinical data of 131 children diagnosed with hospital-associated A. baumannii infections from the pediatrics unit of Shengjing Hospital of China Medical University. We obtained 131 isolates of A. baumannii, determined the minimal inhibitory concentrations (MICs) for common antibiotics, and measured carbapenemase-encoding genes expression using real-time PCR.Results: We isolated 131 strains, 89 of which were carbapenem-resistant (MIC ≥ 8 μg/mL), and 42 carbapenem-sensitive strains. Univariate analysis identified statistically significant differences between the carbapenem-resistant group and the carbapenem-sensitive group for in-hospital days before infection, previous deep vein catheterization, previous urinary catheterization, previous treatment with a carbapenem (meropenem/imipenem), and expression of oxa-51 and oxa-23. Logistic regression analysis of factors associated with carbapenem-resistant A. baumannii infections found significant associations with oxa-23 expression (hazard ratio [HR] 0.005, confidence interval [CI] 95% 0– 0.153, P = 0.002) and previous carbapenem treatment (HR 0.031 CI 95% 0.1– 0.959, P = 0.042). Of 131 patients, 27 died within 30 days. Cox regression analysis of factors associated with 30-day mortality from A.baumannii infections showed that cephalosporin combined with sulbactam (HR 0.271, CI 95% 0.101– 0.723, P = 0.009) was associated with 30-day survival.Conclusion: The expression of oxa-23 and the use of carbapenems were independent risk factors for carbapenem resistance. The use of cephalosporins combined with sulbactam was independently associated with 30-day survival. We recommend using cephalosporins combined with sulbactam in children infected with A. baumannii.Keywords: β-lactamase geen, carbapenem resistance, Acinetobacter baumannii, prognosis, risk factors

In the following systematic review and meta-analyses, we report several conclusions about resistance to carbapenem and polymyxin last-resort antibiotics for treating multidrug-resistant bacterial infections among pregnant women and infants. Resistance to carbapenems and polymyxins is increasing, even in otherwise vulnerable groups such as pregnant women, toddlers, and infants, for whom therapeutic options are limited. In almost all countries, carbapenem-/polymyxin-resistant Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii infect and/or colonize neonates and pregnant women, causing periodic outbreaks with very high infant mortalities. Downregulation of plasmid-borne blaNDM , blaKPC , blaOXA-48 , blaIMP, blaVIM , blaGES-5 , and ompK35/36 in clonal strains accelerates the horizontal and vertical transmissions of carbapenem resistance among these pathogens. New Delhi metallo-β-lactamase (NDM)-positive isolates in infants/neonates have been mainly detected in China and India, while OXA-48-positive isolates in infants/neonates have been mainly detected in Africa. NDM-positive isolates in pregnant women have been found only in Madagascar. Antibiotic therapy, prolonged hospitalization, invasive procedures, mechanical ventilation, low birth weight, and preterm delivery have been common risk factors associated with carbapenem/polymyxin resistance. The use of polymyxins to treat carbapenem-resistant infections may be selecting for resistance to both agents, restricting therapeutic options for infected infants and pregnant women. Currently, low- and middle-income countries have the highest burden of these pathogens. Antibiotic stewardship, periodic rectal and vaginal screening, and strict infection control practices in neonatal ICUs are necessary to forestall future outbreaks and deaths.

Purpose Little is known regarding the burden of infections and clinical practice towards hospitalized patients with limits on life-sustaining measures. We aim to describe the infectious syndromes, clinical care, the emergence of multi-drug resistant organisms and outcomes in this population. Patients and methods Retrospective cohort of patients labeled as support or comfort care in a tertiary care center between 2016–2019. Results A total of 347 patients were included with a mean age of 68.5 years, who were predominantly males (59.94%), bedbound (69.74%), on tube feeding (66.86%), and required indwelling urinary catheters (61.96%). The total number of admissions during the first year was 498, with the mean length of stay being 30 days. The number of infectious syndromes identified during that period was 821episodes, with a mean of 2 infectious syndromes per admission. The most common infection identified was pneumonia (41.66%) followed by urinary tract infections (27.16%). A total of 3891 microbiological cultures were taken with a mean of 5 cultures per infectious syndrome. The most commonly identified pathogens were Gram-negative bacteria (61.03%), with a high rate of multidrug-resistant organisms (MDROs) (48.53%). The one-year mortality was 86.4%. Using carbapenem antibiotic and pneumonia were the independent predictors used for the MDROs. Conclusion Our study reflects the high burden of infections, antimicrobial resistance, and hospital admissions among a population with limited life expectancy. A consensus regarding investigating and managing of infectious syndromes, and antimicrobial prescription is needed to reduce the harms associated with overuse of antimicrobials.

BACKGROUND: Meropenem is a broad-spectrum carbapenem antibiotic approved by the U.S. Food and Drug Administration for use in pediatric patients, including treating complicated intra-abdominal infections (cIAIs) in infants < 3 months of age. The impact of maturation in glomerular filtration rate (GFR) and tubular secretion by renal transporters on meropenem pharmacokinetics, and the effect on meropenem dosing, remains unknown. We applied physiologically based pharmacokinetic (PBPK) modeling to characterize meropenem’s disposition in preterm and term infants. METHODS: An adult meropenem PBPK model was developed in PK-Sim(®) (v. 8) and scaled to infants accounting for renal transporter ontogeny and GFR maturation. The PBPK model was evaluated using 645 plasma concentrations from 181 infants (gestational age 23–40 weeks; postnatal age 1–95 days). PBPK model-based simulations were performed to evaluate meropenem dosing in the product label for infants < 3 months of age treated for cIAIs. RESULTS: Our model predicted plasma concentrations in infants in agreement with the observed data (average fold error of 0.90). The PBPK model-predicted clearance in a virtual infant population was successfully able to capture the post hoc estimated clearance of meropenem in this population, estimated by a previously published model. For 90% of virtual infants, a 4 mg/L target plasma concentration was achieved for > 50% of the dosing interval following product label–recommended dosing. CONCLUSION: Our PBPK model supports the meropenem dosing regimens recommended in the product label for infants < 3 months of age.

Background: Eravacycline is a novel, fully synthetic fluorocycline antibiotic that was evaluated for the treatment of complicated intra-abdominal infections (cIAI) in two phase 3 clinical trials. T...

To the Editor,Multidrug-resistant Pseudomonas aeruginosa is one of the most clinically important opportunistic pathogens, responsible for a wide variety of hospital-acquired infections. Carbapenem ...

Carbapenem resistance in Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa is increasing worldwide, which has led the World Health Organization (WHO) to list these bacteria in the critical priority pathogens group. Infections by such pathogens pose a serious threat to hospitalised patients and are associated with clinical and economic consequences. What worsens the case is the weak pipeline of available antimicrobial agents to treat such infections and the absence of new drugs. The aim of this review was to shed light on all studies tackling carbapenem resistance in Enterobacteriaceae, A. baumannii and P. aeruginosa in the Eastern Mediterranean region, with indication for each country, description of studies timeline, prevalence of carbapenem resistance, and carbapenem resistance-encoding genes detected in these countries.

Background Increasing antimicrobial resistance (AMR) among common bacteria combined with the slow development of new antibiotics has posed a challenge to clinicians. Aim and objective To demonstrate whether antimicrobial and diagnostic stewardship program (ASP and DSP)-related interventions improve antibiotic susceptibilities among common bacteria causing bloodstream infections (BSI) in patients admitted to the intensive care unit (ICU) and whether these resulted in changes in the volume of antimicrobial consumption. Materials and methods We compared the susceptibility patterns of gram-negative bacteria (GNB) and gram-positive cocci (GPC) causing BSI and changes in the volume of antibiotics prescribed for the same before and after 2017 by a retrospective analysis. Results Postintervention, there was increased susceptibility of all GNBs to aminoglycosides; Escherichia coli and Klebsiella spp. to beta-lactambeta-lactamase inhibitors (BLBLI) combinations; and Klebsiella spp. and Pseudomonas spp. to carbapenems. Acinetobacter spp., Klebsiella spp., and Pseudomonas spp. showed improved susceptibility to doxycycline, whereas E. coli and Klebsiella spp. showed significantly improved susceptibility to fluoroquinolones. Among GPCs, there was increased susceptibility of Staphylococcus aureus (levofloxacin, clindamycin, and aminoglycoside), coagulase-negative S. aureus (CoNS) (chloramphenicol, levofloxacin, clindamycin, and aminoglycoside), and enterococci (chloramphenicol, levofloxacin, and clindamycin). There was a significant reduction in usage of antimicrobials for the treatment of GPCs (linezolid, doxycycline, chloramphenicol, levofloxacin, BLBLI, macrolide, and cephalosporin) and GNBs (levofloxacin, cephalosporin, carbapenem, and colistin), which caused BSI. Conclusion The present study illustrated that combined ASP and DSP interventions successfully reversed the resistance pattern of organisms causing BSI and resulted in a reduction in antibiotic utilization. How to cite this article Agarwal J, Singh V, Das A, Nath SS, Kumar R, Sen M. Reversing the Trend of Antimicrobial Resistance in ICU: Role of Antimicrobial and Diagnostic Stewardship. Indian J Crit Care Med 2021;25(6):635-641.

Hospital Acquired Infections (HAIs) are a significant concern for healthcare setups, as it increases the overall cost of treatment, patients stay in hospitals, making them susceptible to secondary and tertiary infections and, sometimes, mortality1. To prevent or control HAIs, evaluating the organisms isolated from the critically maintained areas is considered of epitome importance and everlasting practice in the healthcare industry. Identifying such organisms and screening them for antibiotic resistance is mandatory, but it also helps professionals understand colonization trends. Sensitive areas of healthcare setups were screened monthly from years 2017 to 2020. A total of 4400 samples of hospital hygiene, e.g., intravenous drip stands, ventilator surface, anesthetist's trolley, patient's bed, instrument trolley, etcetera, were collected. Isolated organisms were cultured and screened using the CLSI technique. E. coli, Pseudomonas spp., and Klebsiella spp. were found in both previous to COVID current samples. Multidrug-resistant organisms were subjected to molecular characterization to detect the presence of carbapenem genes. Evaluation data of both pre-and during Coronavirus Disease or COVID-19 were compared. The prevalence of pathogenic (Klebsiella spp., E. coli, and Pseudomonas spp.) and nonpathogenic (Staphylococcus aureus and Bacillus spp.) strains in healthcare setups decreased drastically (Klebsiella spp. from 80% to 20%, E.coli from 90% to 10% and Pseudomonas spp. from 80% to 20%). It is possible only because of the awareness in non-specialists and healthcare workers due to the unforeseen critical situation proving to be a blessing for the future generation. [ABSTRACT FROM AUTHOR] Copyright of Journal of Pure & Applied Microbiology is the property of Dr. M. N. Khan and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Meropenem, a potent carbapenem is considered the first choice for the empirical treatment of severe infections. Being a hydrophilic drug, more than 83% of the administered dose is eliminated through the renal route, and therefore, the kidney status of the patient may have a significant effect on meropenem clearance (CL). Materials and methods The data of 205 samples obtained from 59 patients treated with meropenem at the General Hospital Lahore, Pakistan, was used for the development of a population pharmacokinetic (-popPK) model by using nonlinear mixed-effects modeling software. The effect of age, body weight, creatinine clearance (CRCL), and gender was observed on meropenem CL through a stepwise covariate modeling approach. Simulations of 1,000 mg q8h and 1,500 mg q12h over 3-hour infusion were performed based on the renal status of the patients. Results A two-compartment model was used for popPK analysis, and the values of the pharmacokinetic parameters for CL, V1, V2, and Q were 12.2 L/h, 21.7 L, 7.74 L, and 3.28 L/h, respectively. Meropenem CL was significantly influenced by CRCL, while no significant effect of body weight, age, and sex was observed. Both simulated dosage regimens were equally effective if CRCL of the patient was ≤ 100 mL/min, while 1,000 mg q8h produced better results if CRCL was > 100 mL/min. Conclusion The CL of meropenem depends on the renal status of the patients. The model can be used for dosing simulations based on the CRCL of the patients in order to tailor the dose of meropenem in Pakistani patients.

Purpose Treatment options for urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms are limited other than carbapenem. Accordingly, clinicians should investigate alternative antimicrobial options for limited infection. This study was performed to assess the efficacy of single-dose amikacin and a 7-day oral regimen of amoxicillin/clavulanate for the treatment of acute cystitis caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae. Materials and methods A single-dose amikacin and 7-day oral amoxicillin/clavulanate regimen was given to all patients with acute cystitis or recurrent cystitis between May 2016 and October 2018. We conducted a retrospective cohort study assessing the efficacy of this regimen for the treatment of UTI due to ESBL-producing organisms. Both clinical and laboratory efficacy were assessed a minimum of 7 days and a maximum of 14 days after the completion of treatment. Results A total of 47 patients were enrolled in this study. E. coli and K. pneumoniae were isolated in 44 patients (93.6%) and 3 patients (6.4%), respectively. Of the 47 enrolled, 39 patients (83.0%) showed sterile culture results on follow-up. Thirty-seven patients (78.7%) showed improvement of symptoms. Of 8 patients who showed bacterial persistence, 4 patients showed ESBL-producing E. coli, whereas 4 patients showed non-ESBL E. coli on follow-up cultures. During follow-up, 12 patients experienced the recurrence of acute cystitis with a median recurrence period of 2.5 months. Conclusions The combination of amoxicillin/clavulanate and amikacin may be an alternative to carbapenem treatment in patients with acute cystitis caused by ESBL-producing Enterobacteriaceae.

Currently, there is scarcity of data on whether differences exist in clinical characteristics and outcomes of bloodstream infection (BSI) between venoarterial (VA) and venovenous (VV) extracorporeal membrane oxygenation (ECMO) and whether they differ between Candida BSI and bacteremia in adult ECMO patients. We retrospectively reviewed data of patients who required ECMO for > 48 h and had BSIs while receiving ECMO between January 2015 and June 2020. Cases with a positive blood culture result within 24 h of ECMO implantation were excluded. We identified 94 (from 64 of 194 patients) and 38 (from 17 of 56 patients) BSI episodes under VA and VV ECMO, respectively. Fifty nine BSIs of VA ECMO (59/94, 62.8%) occurred in the first 2 weeks after ECMO implantation, whereas 24 BSIs of VV ECMO (24/38, 63.2%) occurred after 3 weeks of ECMO implantation. Gram-negative bacteremia (39/59, 66.1%) and gram-positive bacteremia (10/24, 41.7%) were the most commonly identified BSI types in the first 2 weeks after VA ECMO implantation and after 3 weeks of VV implantation, respectively. Timing of Candida BSI was early (6/11, 54.5% during the first 2 weeks) in VA ECMO and late (6/9, 66.7% after 3 weeks of initiation) in VV ECMO. Compared with bacteremia, Candida BSI showed no differences in clinical characteristics and outcomes during VA and VV ECMO, except the significant association with prior exposure to carbapenem in VA ECMO (vs. gram-negative bacteremia [P = 0.006], vs. gram-positive bacteremia [P = 0.03]). Our results suggest that ECMO modes may affect BSI clinical features and timing. In particular, Candida BSI occurrence during the early course of VA ECMO is not uncommon, especially in patients with prior carbapenem exposure; however, it usually occurs during the prolonged course of VV ECMO. Consequently, routine blood culture surveillance and empiric antifungal therapy might be warranted in targeted populations of adult ECMO patients, regardless of levels of inflammatory markers and severity scores.

Background The frequency of urinary tract infections (UTIs) caused by community-acquired extended-spectrum β-lactamase (CA-ESBL)-producing Enterobacteriaceae is increasing worldwide. Increased carbapenem use may lead to selection of carbapenem-resistant organisms, resulting in dire consequences for hospitals. We compared the outcomes of non-carbapenem antimicrobial therapy on UTIs caused by CA-ESBL-producing and non-producing Escherichia coli (E. coli) in infants younger than 6 months of age. Methods We conducted a retrospective chart review, from January 2010 to December 2018, in infants (0–6 months old) with diagnosed UTIs caused by CA-ESBL-producing and non-producing E. coli at the Pusan National University Children's Hospital. Chart reviews were completed for patients whose urine sample had been collected using urinary catheterization. We treated all patients using non-carbapenem antimicrobials. Two weeks after therapy completion, clinical states were evaluated. Results There were 105 and 582 patients diagnosed with UTIs caused by CA-ESBL-producing and non-producing E. coli, respectively. The mean age at diagnosis in ESBL and non-ESBL groups was 2.7 ± 1.6 and 2.8 ± 1.1 months (P = 0.711), respectively. There were no significant differences between ESBL and non-ESBL groups in the duration of fever (1.2 ± 0.5 and 1.2 ± 0.4 days, respectively, P = 0.761) or clinical cure states post therapy (101/105 and 567/582, respectively, P = 0.513). Conclusion This study found no significant differences in treatment outcomes between ESBL and non-ESBL groups treated with non-carbapenem antimicrobials. Therefore, initially administered non-carbapenem antimicrobials can be continued in patients with UTIs caused by CA-ESBL-producing E. coli who show clinical improvement.

BACKGROUND Several case reports and retrospective studies have indicated that carbapenems decrease the plasma concentration of valproic acid (VPA). This retrospective study examines the effect of carbapenems on VPA levels, and explores whether the drug-drug interaction can influence the liver function of patients. METHODS The data of 141 patients were collected from the Department of Neurosurgery at Shanxi Bethune Hospital from January 2018 to December 2019. We compared the VPA levels between the VPA monotherapy group and VPA + carbapenem group to evaluate the influence of carbapenem antibiotics on the plasma concentration of VPA. We also compared the liver injury rate of the VPA monotherapy group, VPA + meropenem group, and VPA + imipenem group to evaluate the influence of concomitant use of VPA with carbapenem antibiotics on liver function. RESULTS The VPA serum concentration in the VPA + meropenem group was 22.32±21.77 µg/mL, which was markedly lower than that in the VPA monotherapy group (i.e., without carbapenems) (65.17±21.49 µg/mL) (P

Background Clostridioides difficile was listed as an urgent antimicrobial resistance (AMR) threat in a report by the CDC in 2019. AMR drives the evolution of C. difficile and facilitates its emergence and spread. The C. difficile Antimicrobial Resistance Surveillance (CDARS) study is nationwide longitudinal surveillance of C. difficile infection (CDI) in Australia. Objectives To determine the antimicrobial susceptibility of C. difficile isolated in Australia between 2015 and 2018. Methods A total of 1091 strains of C. difficile were collected over a 3 year period by a network of 10 diagnostic microbiology laboratories in five Australian states. These strains were tested for their susceptibility to nine antimicrobials using the CLSI agar incorporation method. Results All strains were susceptible to metronidazole, fidaxomicin, rifaximin and amoxicillin/clavulanate and low numbers of resistant strains were observed for meropenem (0.1%; 1/1091), moxifloxacin (3.5%; 38/1091) and vancomycin (5.7%; 62/1091). Resistance to clindamycin was common (85.2%; 929/1091), followed by resistance to ceftriaxone (18.8%; 205/1091). The in vitro activity of fidaxomicin [geometric mean MIC (GM) = 0.101 mg/L] was superior to that of vancomycin (1.700 mg/L) and metronidazole (0.229 mg/L). The prevalence of MDR C. difficile, as defined by resistance to ≥3 antimicrobial classes, was low (1.7%; 19/1091). Conclusions The majority of C. difficile isolated in Australia did not show reduced susceptibility to antimicrobials recommended for treatment of CDI (vancomycin, metronidazole and fidaxomicin). Resistance to carbapenems and fluoroquinolones was low and MDR was uncommon; however, clindamycin resistance was frequent. One fluoroquinolone-resistant ribotype 027 strain was detected.

Carbapenems are currently the only active beta-lactams effective against the ESBL producing pathogens; this has led to an increase in their use not only for documented infections but also for empirical treatment of acquired infections in ICU patients. Thus, there is a selective pressure for carbapenem resistance in intensive care units of tertiary care hospitals. Carbapenem resistant infections are associated with high morbidity & mortality. 1. To screen for carbapenem resistance among gram negative infections in ICU patients by disc diffusion & confirmation by Vitek 2 system; 2: To detect the carbapenemase production by phenotypic methods; 3: To confirm the presence of resistant gene by PCR; 4: To find out the attributable risk factors from the clinical history of such patients; 5: To follow up & estimate mortality rate in such infections and its statistical correlation A total of 160 gram negative isolates [E.coli(71), Klebsiella(63), Acinetobacter(10), Pseudomonas(9) and Enterobacter(7)] from patients of various intensive care units were screened by disc diffusion out of which 53(33.12%) were carbapenem resistant. Resistant isolates were further tested by Vitek 2 system for determination of MICs, Modified Hodge test(MHT) and Combined Disc test(CDT) for carbapenemase production and subjected to multiplex PCR for detection of resiatant gene i.e., bla NDM-1, bla VIM, bla IMP and bla KPC. Follow up of all the cases till the end of hospital stay was done and mortality rate was calculated.Results: 53 isolates(33.12%) were carbapenem resistant, 17 isolates were MHT positive while 39 were CDT positive. 24 isolates [E.coli(12), Klebsiella(7), Acinetobacter(3), Pseudomonas(1) and Enterobacter(1)] showed the presence of NDM-1 gene on PCR. Gentamicin(35%), Amikacin (45%), Tigecycline(88%) & Colistin(100%) were sensitive for carbapenem resistant GNBs. Mortality in carbapenem sensitive infections in ICUs was 21% whereas resistant infections showed 37% (p value Conclusion: 45% of carbapenem resistance is due to presence of NDM-1 gene, E.coli was the commonest isolate. Other mechanisms of resistance such as excessive ESBL production, porin loss may be responsible for resistance in remaining isolates. Effective infection control measures should be taken to prevent the spread of these super bugs in a ICU.

Purpose To evaluate risk factors for epileptic seizures or status epilepticus (SE) in patients concomitantly receiving valproic acid (VPA) and carbapenems. Materials and methods Adult patients in the intensive care units (ICUs) who concomitantly received VPA and carbapenems from 2007 to 2017 were included. The impacts of different carbapenems on serum concentration of VPA were compared. Results Among 162 patients included, 104 (64.2%) and 45 (27.8%) developed epileptic seizures and SE, respectively. The risk factors for epileptic seizures were age (per year increase, adjusted odds ratio [aOR], 1.03), initial antiepileptic regimen (monotherapy and polytherapy, aOR, 0.43 and 0.18, respectively), and VPA serum concentration after concomitant carbapenem administration (per 1 μg/mL increase, aOR, 0.96). VPA serum concentration after concomitant carbapenem administration was an independent risk factor for SE (per μg/mL increase, aOR, 0.98). Concomitant imipenem/cilastatin administration did not significantly decrease VPA serum concentration compared to that by meropenem or ertapenem. The length of stay and number of days on ventilation after concomitant carbapenem administration in the ICUs were significantly more in those with epileptic seizures or SE. Conclusions Carbapenems decreased VPA serum concentration and increased the risk of epileptic seizures and SE, which led to increased length of ICU stay.

Background The optimal antibiotic regimen for the medical management of acute appendicitis remains unknown due to a lack of head-to-head comparisons between different antibiotic regimens. Methods We systematically searched the PubMed, EMBASE, Scopus and Cochrane Central Register of Controlled Trials databases from their inception through to August 2020. We selected randomized controlled trials (RCTs) or observational studies comparing antibiotic therapy and appendectomy as the initial treatment for adult or paediatric patients with acute appendicitis. We performed a Bayesian network meta-analysis (NMA) to obtain the indirect comparison results between different antibiotic regimens by employing the group managed by surgery as a common comparator. Antibiotic regimens were classified into three categories: those including a carbapenem; those including a cephalosporin; and those including a β-lactam/β-lactamase inhibitor combination. Results A total of 9 RCTs (adults, n = 8; paediatrics, n = 1) and 12 observational studies (adults, n = 3; paediatrics, n = 9) were included in the NMA, with a total of 4551 patients. The most commonly administered regimen was a β-lactam/β-lactamase inhibitor combination (9/21; 43%), followed by a cephalosporin (7/21; 33%) or a carbapenem (5/21; 24%). The NMA indicated that surgery significantly increased 1 year treatment success, compared with cephalosporins [OR: 16.79; 95% credible interval: 3.8–127.64] or β-lactam/β-lactamase inhibitor combinations (OR: 19.99; 95% credible interval: 4.87–187.57), but not carbapenems (OR: 3.50, 95% credible interval: 0.55–38.63). In contrast, carbapenems were associated with fewer treatment-related complications compared with surgery (OR: 0.12; 95% credible interval: 0.01–0.85). Conclusions Carbapenems might be recommended as the initial antibiotic regimen for the non-operative management of adult patients with acute appendicitis. Nevertheless, due to the imprecise estimates in our NMA, additional RCTs are needed to corroborate these findings, especially for paediatric patients.

OBJECTIVE To estimate the prevalence of extended-spectrum cephalosporin-, carbapenem-, and fluoroquinolone-resistant bacteria of the family Enterobacteriaceae in the feces of hospitalized horses and on hospital surfaces. SAMPLE Fecal and environmental samples were collected from The Ohio State University Galbreath Equine Center (OSUGEC) and a private referral equine hospital in Kentucky (KYEH). Feces were sampled within 24 hours after hospital admission and after 48 hours and 3 to 7 days of hospitalization. PROCEDURES Fecal and environmental samples were enriched, and then selective media were inoculated to support growth of Enterobacteriaceae bacteria that expressed resistance phenotypes to extended-spectrum cephalosporins, carbapenems, and fluoroquinolones. RESULTS 358 fecal samples were obtained from 143 horses. More samples yielded growth of Enterobacteriaceae bacteria that expressed resistance phenotypes (AmpC β-lactamase, OR = 4.2; extended-spectrum beta-lactamase, OR = 3.2; and fluoroquinolone resistance, OR = 4.0) after 48 hours of hospitalization, versus within 24 hours of hospital admission. Horses hospitalized at KYEH were at greater odds of having fluoroquinolone-resistant bacteria (OR = 2.2). At OSUGEC, 82%, 64%, 0%, and 55% of 164 surfaces had Enterobacteriaceae bacteria with AmpC β-lactamase phenotype, extended-spectrum beta-lactamase phenotype, resistance to carbapenem, and resistance to fluoroquinolones, respectively; prevalences at KYEH were similarly distributed (52%, 32%, 1%, and 35% of 315 surfaces). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that antimicrobial-resistant Enterobacteriaceae may be isolated from the feces of hospitalized horses and from the hospital environment. Hospitalization may lead to increased fecal carriage of clinically important antimicrobial-resistance genes.

Introduction: Klebsiella pneumoniae are among the most common cause of urinary tract infections such as cystitis and pyelonephritis. These multi-drug resistant K. pneumoniae are producers of extended spectrum beta-lactamases (ESBL) that are capable of hydrolyzing beta-lactams and non-beta-lactams. This laboratory-based study sought to establish the increase of ESBL-producing K. pneumoniae in multi-drug resistant urinary tract infections and determine the effective antibiotic treatment options. Methods: One hundred and seventy five K. pneumoniae isolates obtained from urine cultures were randomly collected and the combined disc synergy method was used to determine the ESBL-producing K. pneumoniae. The Vitek 2 system (bioMérieux, France) was used to perform antimicrobial susceptibility testing of 17 commonly used antibiotics. The data from the work was collated and statistically analysed using the chi-square test and Mann-Whitney U test. P values < 0.05 were considered significant. Results: Of the 175 K. pneumoniae responsible for urinary tract infections, 73.7% were producing ESBL suggesting that most urinary tract infections caused by K. pneumoniae will be multi-drug resistant. The antimicrobial resistance differences between ESBL-producing and non-ESBL-producing Klebsiella pneumoniae indicated a significance difference with p < 0.05. This study indicated that imipenem and amikacin are the antibiotic of choice for the treatment of multi-drug resistant urinary tract infections caused by ESBL-producing K. pneumoniae. Cephalosporins and nitrofurantoin are suitable for the treatment of urinary tract infections due to non-ESBL-producing K. pneumoniae. Conclusion: This study indicated that imipenem (carbapenem) and amikacin are the antibiotic of choice for the treatment of multi-drug resistant urinary tract infections caused by ESBL-producing K. pneumoniae. The third and fourth generation cephalosporins and nitrofurantoin are suitable for the treatment of urinary tract infections due to non-ESBL-producing K. pneumoniae. Rational use of antibiotics and evidence based antibiotic prescription will help to control the spread of resistance by ESBL-producing K. pneumoniae. There is the need to intensify research in the use of natural products to treat multi-drug resistant urinary tract infections emanating from ESBL-producing K. pneumoniae

Background Previous meta-analyses suggested that treating hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), with empiric carbapenems was associated with lower mortality rates but higher rates of clinical failure for pseudomonal pneumonia. This study was an updated meta-analysis with sensitivity analyses and meta-regression to better understand the impact of carbapenem use in HAP/VAP. Research Question What is the efficacy of carbapenems for empiric treatment of nosocomial pneumonia? Study Design and Methods Databases were searched for randomized controlled studies evaluating empiric treatment for HAP and/or VAP, and studies were included comparing carbapenem- vs non-carbapenem-containing regimens. The primary outcome was all-cause mortality. Secondary outcomes included subgroup stratification and resistance development. Results Of 9,140 references, 20 trials enrolling 5,489 patients met inclusion criteria. For mortality, carbapenem use had a risk ratio (RR) of 0.84 (95% CI, 0.74-0.96; P = .01). Stratified according to VAP proportion ( 66%), RRs were 0.95 (95% CI, 0.77-1.17; P = .66), 0.78 (95% CI, 0.57-1.07; P = .13), and 0.81 (95% CI, 0.65-0.99; P = .04), respectively. Stratified according to severity, only groups with Acute Physiology and Chronic Health Evaluation II scores Interpretation Carbapenem-based empiric regimens were associated with lower mortality rates compared with non-carbapenems, largely driven by trials of VAP. The mortality effect was not observed in trials with high disease severity and was not associated with Pseudomonas. The mortality difference was observed mainly in studies that used ceftazidime as control. There was a trend toward increasing resistance associated with carbapenems. Trial Registry International Prospective Register of Systematic Reviews; No. CRD42018093602; URL: https://www.crd.york.ac.uk/prospero/ .

Background: Superinfection is a new isolate pathogen after 48 h of antibiotic treatment or within one week of treatment discontinuation. In many studies carbapenem and piperacillin–tazobactam were associated with high risk of superinfection. Aim: To evaluate the rate of superinfections during carbapenem and piperacillin/tazobactam treatment. Also, to identify risk factors for superinfections. Methods: A Retrospective observational study was conducted in King Abdulaziz Medical City. Approval from the institutional Review Board was obtained. The study included all adult patient treated with carbapenem or piperacillin/tazobactam for more than 72 h. Univariate and multivariate analysis was conducted to compare piperacillin/tazobactam versus carbapenems and to identify the associated risk factor to develop superinfection. Finding: 507 patients were included in this study. The mean age of the patients was 61 years ± 19.33. Of these, 278 received carbapenems and 229 received piperacillin/tazobactam. In univariate analysis superinfections were significantly higher with carbapenems compared with piperacillin–tazobactam (28.77% versus 20.96%; P value = 0.044). After adjustment of cofounders in multivariate analysis, presence of tracheostomy, endotracheal ventilation, foley catheter and duration of antibiotic were associated with higher risk to developed superinfection adjusted odd ratio (aOR) 3.23 (95% CI,1.39–7.52) P < 0.01, aOR 2.556 (95% CI,1.30–5.02) P < 0.01, aOR 2.20 (95% CI,1.35–3.61) P < 0.001, aOR 1.051(95% CI,1.02–1.08) P < 0.001 respectively, but not carbapenems use aOR 1.052 (95% CI,0.657–1.685). Conclusions: The use of carbapenems were not associated with higher risk to developed superinfection. The most important risk factors associated with superinfection were presence of tracheostomy, endotracheal mechanical ventilation, Foley catheter and the duration of antibiotics.

Objectives The aim of this study was to investigate the clinical efficacy and safety of cefiderocol in the treatment of acute bacterial infections. Methods The PubMed, Embase and Cochrane Library databases as well as the clinical trials registries of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched up to 8 November 2020. Only randomised controlled trials (RCTs) that compared the treatment efficacy of cefiderocol with that of other antibiotics for adult patients with acute bacterial infections were included in this meta-analysis. The primary outcome was clinical response at test of cure (TOC). Results Three RCTs, including one phase 2 and two phase 3 trials, were included. No significant difference in clinical response rate was observed between cefiderocol and comparators [odds ratio (OR) = 1.04]. In a subgroup analysis, no significant difference was observed in the clinical response at TOC between cefiderocol and comparators in patients with nosocomial pneumonia (OR = 0.92) or complicated urinary tract infection (OR = 1.28). In addition, all-cause mortality at Days 14 and 28 did not differ between the cefiderocol and control groups (14-day mortality, OR = 1.25; 28-day mortality, OR = 1.12). Furthermore, cefiderocol was associated with similar microbiological response to comparators at the TOC assessment (OR = 1.44). Finally, cefiderocol was associated with a similar risk of adverse events as comparators. Conclusion Cefiderocol can achieve similar clinical and microbiological responses as comparators for patients with serious bacterial infections. In addition, cefiderocol shares a safety profile similar to that of comparators.