Search

Introduction Gram-negative bacteria are an important etiological factor of broad-spectrum nosocomial infections. The spread of multidrug-resistant strains, both belonging to the order Enterobacterales and non-fermenting bacilli Pseudomonas aeruginosa, is a serious challenge nowadays for medicine. Investigating new therapeutic options and monitoring the antibiotic susceptibility of bacteria is an important part of preventing the development of infections with multi-drug resistant strains. The aim of the study was to compare the in vitro activity of the combination of ceftazidime and avibactam with the most commonly used antibiotics in Poland for the treatment of infections caused by Gram-negative Enterobacterales and P. aeruginosa, as part of the ATLAS research program. Material and methods In the study the sensitivity of 1,677 Enterobacterales strains and 500 non-fermenting P. aeruginosa strains, isolated in 2014-2018 in the centers participating in the program, to ceftazidime with avibactam and other antibiotics used to treat infections caused by Gram-negative bacilli were analyzed. Results Almost 99% (98.9%) of the Enterobacterales strains, including the strains producing ESBL--type beta-lactamases (96.9%), were susceptible to ceftazidime with avibactam. A high percentage of Escherichia coli and Klebsiella pneumoniae isolates were susceptible to ceftazidime with avibactam: 99.8% and 98.9%, respectively, including ESBL-positive strains of the same species, 98.5%, and 98.7%, respectively. The susceptibility of P. aeruginosa strains to ceftazidime with avibactam has evolved at the level of 91.7%, which placed ceftazidime with avibactam the second best, after colistin, antibiotic against these bacteria. Conclusions The presented results, together with the pharmacokinetic, pharmacodynamic, clinical, and safety results published so far, indicate that the combination of ceftazidime with avibactam is a valuable treatment option for infections caused by Enterobacterales and P. aeruginosa, including infections with multidrug-resistant strains. [ABSTRACT FROM AUTHOR]

To describe and compare the characteristics of necrotizing fasciitis (NF) in patients with and without haematological malignancy. All adult patients diagnosed with NF and treated at our hospital were included (January 2010–March 2019). Diagnosis was based on intraoperative findings or consistent clinical/radiological characteristics, and patients were classified as group A (with haematological malignancy) or group B (without haematological malignancy). Student's t (quantitative), Fisher's exact (qualitative), and Kaplan-Meyer tests were used for the statistical analysis. The study included 29 patients: 8 in group A and 21 in group B. All haematological patients had severe neutropenia (0.2 [0.02–0.5] ×109 cells/L; p < 0.001) and positive blood cultures (100% vs. 61.9%; p = 0.04) at diagnosis. Gram-negative bacilli NF was more common in group A (87.5% vs. 9.5%; p = 0.001), predominantly due to Escherichia coli (50% vs. 9.5%; p = 0.056). Surgical treatment was less common in haematological patients (5 [62.5%] vs. 21 [100%]; p = 0.015). Overall, 9 (31%) patients died: 4 (50%) in group A and 5 (23.8%) in group B (p = 0.17). The univariate analysis showed that mortality tended to be higher (OR 3.2; 95%CI 0.57–17.7; p = 0.17) and to occur earlier (2.2 ± 2.6 vs. 14.2 ± 19.9 days; p = 0.13) in haematological patients. The LRINEC index > 6 did not predict mortality in either group. In our study, NF in patients with haematological malignancies was mainly due to Gram-negative bacilli, associated to high and early mortality rates. In our experience, the LRINEC scale was not useful for predicting mortality. [ABSTRACT FROM AUTHOR]

Introduction: Studies have shown that ceftriaxone-sulbactam-EDTA combination is a promising therapeutic option as carbapenem sparer in cases of infections caused by ESBL and MBL producing pathogens, respectively. This study is aimed to generate preliminary data on in-vitro susceptibility profile of clinical multi-drug resistant (MDR) Gram-negative bacterial isolates to ceftriaxone-sulbactam-EDTA combination. Materials and Methods: A cross-sectional study was conducted from January 1st, 2019 to October 31st, 2019. Antibiotic susceptibility data (including that of ceftriaxone-sulbactam-EDTA combination) of 200 multi-drug-resistant Gram-negative bacterial isolates obtained from various nonrepetitive clinical samples of patients of all age groups and sexes, was retrospectively analyzed. All clinical samples were processed aerobically as per standard guidelines, and the bacterial isolates obtained in culture were identified by conventional biochemical methods. Antibiotic susceptibility testing of bacterial isolates was performed using the modified Kirby Bauer disk diffusion method, the results of which were interpreted as per the Clinical and Laboratory Standards Institute (CLSI) guidelines 2019. In vitro susceptibility test results of ceftriaxone-sulbactam-EDTA combination, disks were interpreted as per the manufacturer's instructions. Results: Acinetobacter spp. was the most common isolate (53%), followed by Escherichia coli (20.5%), Klebsiella spp. (17.5%), Pseudomonas aeruginosa (16.5%), Citrobacter spp. (2%), and Proteus spp. (1%), respectively. 99.1%, 92.7%, 88.6%, and 69.3% of Acinetobacter spp., E. coli, Klebsiella spp. and P. aeruginosa, respectively, were susceptible to ceftriaxone-sulbactam-EDTA combination disks. Conclusions: The preliminary data generated by our study could be an eye-opener for clinicians practicing in this part of the country and should prompt further investigation in the form of clinical trials. [ABSTRACT FROM AUTHOR]

Background: Over the past two decades, antibiotic resistance has increased significantly in Gram-negative bacilli (GNB) and in many cases has been linked with increased mortality and health-care costs. The multidrug-resistant (MDR) bacteria such as Pseudomonas aeruginosa (P. aeruginosa) and Acinetobacter baumannii (A. baumannii) and various Enterobacteriaceae including Klebsiella, and Escherichia coli can cause severe and often deadly infections those are frequently reported in the hospitals and clinics. This study aimed to investigate the resistance patterns of GNB commonly encountered in our hospital as well as the outcome of the infection caused by these bacterial agents. Materials and Methods: The samples were processed from a culture and sensitivity test. The isolates were identified primarily by conventional method and then confirmed by Vitek 2 compact system, also antimicrobial sensitivity test was performed using the Vitek 2 compact system. Results: A total of 293 samples were collected from adult patients admitted to AL-Sader Medical City, Najaf, Iraq, from July 1, 2019, to January 7, 2020. The Gram-negative isolates were collected from clinical samples that included urine, wound swab, ear swab, sputum, and pus. Urine specimens accounted for a majority 163 (55.64%) of the clinical samples which yielded GNB, followed by wound swab 75(25.59%), ear swab 29 (9.89%), sputum 22 (7.51%), and pus 4 (1.37%). E. coli was the predominated bacteria 150 (51.19%) followed by P. aeruginosa 59 (20.13%) and Klebsiella pneumoniae 50 (17.06%). The remaining 34 (11.59%) of isolates included Proteus mirabilis 15 (5.11%), A. baumannii 10 (3.41%), and Enterobacter spp. 9 (3.07%). E. coli was leading microorganism isolated from pus 4 (100%) and urine 119 (73.0%); P. aeruginosa was dominant bacteria isolated from ear swab 18 (62.06%) and wound swab 26 (34.66%); and Klebsiella pneumoniae was common microorganism isolated from sputum 9 (40.90%). GNB were showed variable resistant to different types of antibiotics, but E. coli and K. pneumoniae were exhibited high resistance to ceftazidime (CAZ) 119 (58.62%) and 43 (21.18%); cefepime (FEP) 89 (60.13%) and 30 (20.27%); and ceftriaxone (CRO) 74 (62.18%) and 25 (21.00%), respectively. All members of GNB were shown high resistant to CAZ 203 (19.80%), FEP 148 (14.44%), and CRO 119 (11.61%) compared with other types of antibiotics. Out of 293 GNB, 119 (40.61%) isolated were exhibited MDR microorganisms (MDROs). Conclusions: We can conclude from our study that most GNB were isolated from urine samples. E. coli was the predominated bacteria followed by P. aeruginosa. GNB were showed variable resistance to a different type of antibiotics, but all members of GNB were shown high resistance to CAZ 203 (19.80%), FEP 148 (14.44%), and CRO 119 (11.61%). The isolates were exhibit multi-drug resistant microorganisms. [ABSTRACT FROM AUTHOR]

Introduction: Bioluminescence is the ability of certain organisms to transform chemical energy into light energy through various biochemical processes. Objective: Isolation and identification for the first time of luminescent bacteria of superficial marine water, and the identification of marine luminescent dinoflagellates of Isla del Coco National Park, Costa Rica. Methods: Samples of seawater obtained by diving at 20 m and at a surface level of 13 sites were collected. On the other hand, phytoplankton samples collected from the surface up to 30 m deep were analyzed in the surroundings of 8 sites of Cocos Island, and several luminescent species belonging to the genera Ornithocercus and Ceratocorys were determined. Results: Seven luminescent bacterial isolates were obtained, they were identified and characterized biochemically by means of an automated platform (Vitek) with high levels of confidence, they were taxonomically located within the genus Vibrio, 2 species: V. alginolyticus and V. parahaemolyticus, in addition, some isolates presented resistance to the antibiotic ampicillin and 100% hemolytic capacity. This research shows evidence of the presence of marine microscopic species in Cocos Island, Costa Rica, capable of presenting the phenomenon of luminescence, so that further study would be relevant in terms of the importance of these microorganisms in the production of metabolites secondary and as indicators of harmful algal blooms, so it is necessary to conduct more scientific research to determine their biotechnological potential. Conclusions: In the same way, the results obtained in this investigation suggest expanding the collection and isolation of luminescent microorganisms, accompanied by a biochemical and molecular characterization, in order to explore the microbial diversity associated with luminescence events and determine the environments in which that these species develop. [ABSTRACT FROM AUTHOR]

The emergence of blaNDM particularly in Gram-negative bacteria is a burden on the health care system in developing countries. Hence, this study was initiated to screen New Delhi Metallo-β-lactamase (NDM)-producing Gram-negative bacterial strains from neonatal intensive care unit (NICU) of an Indian Hospital. A total of 18 blaNDM-producing isolates were detected in the present study. Out of 18 blaNDM variant isolates, 6 were Klebsiella pneumoniae, 4 Escherichia coli, 2 Enterobacter aerogenes, 1 Acinetobacter lwoffii, 1 Enterobacter cloacae, 3 Acinobacter baumannii, and 1 Cedecea davisae from NICU, showing resistance against all antibiotics, except colistin and polymixin. The transferability of resistance determinants was tested by conjugation. Transfer of blaNDM-producing strains was successful in all 18 strains. In the case of transconjugants, the minimum inhibitory concentration values were found to decrease. The blaNDM-producing isolates contained detectable plasmids of size 66, 38, and 6 kb. Plasmi/d-based replicon typing revealed the incompatibility types Inc (A/C, FIIA, FIC, K, F, W, FIA, P, X, FIB, B/O) in blaNDM-carrying isolates. This study revealed the outbreak of multiple variants of blaNDM (13 NDM-1, 4 NDM-5, and 1 NDM-7). Moreover, other resistance markers, viz. blaOXA-1, blaCMY-1, blaVIM-1, and blaSHV-1 coassociated with blaNDM were also found. In this study, we reported NDM–producing C. davisae as a first report to the best of our knowledge. This study is an attempt to reveal the dissemination of blaNDM isolated from neonates in NICU and their efficient transferability among Gram-negative bacilli through horizontal gene transfer. [ABSTRACT FROM AUTHOR]

Community-acquired Gram-Negative (GN) bacteremia caused more morbidity and mortality recently in children. The increasing drug resistance was also an important issue. However, published reference was few about children. We conducted a retrospective study to collect febrile patients with blood culture from a pediatric emergency department during 2007∼2013, and exclude cases ever admitted to hospital within 14 days. These blood cultures all showed single GN organism. The demographic characteristics of enrolled patients and the antibiogram of pathogens were recorded, and then were compared statistically to find out the immediate and appropriate antibiotics. Total 143 sets of blood culture were GN bacilli and the median age of cases was 2 (IQR, 1-5) years old. Male gender was predominant. Non-fermenting Gram-negative bacilli group (NFGNB spp.), Salmonella spp. and Escherichia coli were first three common pathogens respectively. However, total 37 cases of NFGNB spp. other than Pseudomonas aeruginosa were the possible pathogens. By multiple logistic regression analysis, lower hemoglobin and higher alanine aminotransferase were significant difference between common pathogens and possible ones. Besides, the prevalent age regarding resistant strains of Escherichia coli and Pseudomonas aeruginosa were both focused on less than 1 year old. However, Salmonella spp. were prevalent in the age from 1 to 3 years old. For different age groups, Salmonella spp. and Escherchia coli were the most common pathogens of community-acquired GN bacteremia. For infants, Pseudomonas aeruginosa sepsis and resistant strain of Escherchia coli should be alert, and broader antibiotics should be considered. [ABSTRACT FROM AUTHOR]

The plasmid-mediated quinolone resistance (PMQR) genes have changed the resistance pattern to quinolones, especially among Enterobacteriales. The dissemination of these genes in Latin American countries, where the prescription of fluoroquinolones is high, has been described in several studies; however, no review of the impact of PMQR in this continent has been conducted. This review summarized current knowledge about the circulation of PMQR among Enterobacteriales in Latin American. After the search and selection, 61 articles were included in the study. Most of studies reported PMQR genes among Enterobacteriales from human (47/61, 77%) and animal (18/61, 29.5%) samples, recovered mainly in Brazil (23/61, 37.7%), Mexico (11/61, 18%), and Uruguay (7/61, 11.5%). Nine different PMQR genes (qnrA, qnrB, qnrS, qnrD, qnrE, aac-(6′)-Ib-cr, oqxA, oqxB, and qepA) were found in Latin America, with aac (6′)-Ib-cr (37/61, 60.6%) and qnrB (26/61, 42.6%) being the most frequently reported. Escherichia coli (40/61, 65.6%) was the species most frequently reported to carry a PMQR gene, followed by Klebsiella pneumoniae (24/61, 39.3%), Enterobacter cloacae (15/61, 24.6%), and Salmonella spp. (14/61, 22.9%). Thus, this review provides important information which might help in designing measures to control the spread of quinolone resistance determinants on this continent. [ABSTRACT FROM AUTHOR]

Omneya M Helmy, Mona T Kashef Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt Objectives: We set out to investigate the prevalence, different mechanisms, and clonal relatedness of multidrug resistance (MDR) among third-generation cephalosporin-resistant Gram-negative clinical isolates from Egypt.Materials and methods: A total of 118 third-generation cephalosporin-resistant Gram-negative clinical isolates were included in this study. Their antimicrobial susceptibility pattern was determined using Kirby–Bauer disk diffusion method. Efflux pump-mediated resistance was tested by the efflux-pump inhibitor-based microplate assay using chlorpromazine. Detection of different aminoglycoside-, β-lactam-, and quinolone-resistance genes was done using polymerase chain reaction. The genetic diversity of MDR isolates was investigated using random amplification of polymorphic DNA.Results: Most of the tested isolates exhibited MDR phenotypes (84.75%). The occurrence of efflux pump-mediated resistance in the different MDR species tested was 40%–66%. Acinetobacter baumannii isolates showed resistance to most of the tested antibiotics, including imipenem. The blaOXA-23-like gene was detected in 69% of the MDR A. baumannii isolates. The MDR phenotype was detected in 65% of Pseudomonas aeruginosa isolates, of which only 23% exhibited efflux pump-mediated resistance. On the contrary, efflux-mediated resistance to piperacillin and gentamicin was recorded in 47.5% of piperacillin-resistant and 25% of gentamicin-resistant MDR Enterobacteriaceae. Moreover, the plasmid-mediated quinolone-resistance genes (aac(6’)-Ib-cr, qnrB, and qnrS) were detected in 57.6% and 83.33% of quinolone-resistant MDR Escherichia coli and Klebsiella pneumoniae isolates, respectively. The β-lactamase-resistance gene blaSHV-31 was detected for the first time in one MDR K. pneumoniae isolate from an endotracheal tube specimen in Egypt, accompanied by blaTEM-1, blaCTX-M-15, blaCTX-M-14, aac(6’)-Ib-cr, qnrS, and multidrug efflux-mediated resistance.Conclusion: MDR phenotypes are predominant among third-generation cephalosporin-resistant Gram-negative bacteria in Egypt and mediated by different mechanisms, with an increased role of efflux pumps in Enterobacteriaceae. Keywords: multidrug resistance, efflux pump, Egypt, Gram-negative bacilli, RAPD typing

AbstractOne of the major problems in hospitals resistance of pathogenic bacteria , including bacteria that cause urinary tract infections(UTI), antimicrobial substances , the problem of increased costs of treatment , treatment failure and mortality rates are increasing.The purpose of this research is to identify multidrug-resistant Gram-negative bacilli of urinary tract infections with antibiotics and the effect of silver nanoparticles on them.Planting 240 clinical samples from patients admitted to two hospitals ( Fatemiyeh , Besat) within 6 months of 1395 a total of 150 gram negative bacilli of urinary tract infections was isolated. To determine antibiotic resistance of these bacteria, disk diffusion method was used, and their susceptibility was evaluated according to the CLSI(clinical and laboratory Standards Institute) . Gram-negative bacilli isolated were prepared and inhibition zone diameter was measured.The most common bacteria Escherichia coli was isolated and lowest frequencies of the Proteus vulgaris. All of the samples to a solution of silver nanoparticles at concentrations 200 ppm 100 ppm and were sensitive. Pseudomonas aeruginosa (30 mm) and Enterobacter aerogenes (27 mm) maximum diameter in the presence of silver nanoparticles showed 800 ppm.Conclusion: The results show that silver nanoparticles can have an inhibitory effect on all tested Gram-negative bacilli , and the concentration of nanoparticles , the diameter of the growth of Gram-negative bacilli of urinary tract infections resistant to multiple antibiotics increases.Key words: Gram-negative bacilli, Silver nanoparticles, Urinary Tract Infection,Antibiotic Resistance, Hamedan

In Ghana, surveillance efforts on antibiotic resistance so far have not covered carbapenem resistance. In this study, our aim was to apply phenotypic and genotypic methods to identify and characterize carbapenem-resistant (CR) Gram-negative bacteria from the hospital environment in Ghana. A collection of 3840 isolates of Gram-negative bacilli infections from various clinical specimens was screened for carbapenem resistance by disc diffusion for imipenem, meropenem, and doripenem. Minimum Inhibitory Concentration (MIC) of the CR isolates was determined by E-test for the three carbapenems. All the CR isolates were further screened for carbapenemase activity by modified Hodge and boronic acid disc synergy tests. The CR isolates were investigated for the presence of carbapenemase and extended-spectrum beta-lactamase genes by PCR and confirmed by sequencing. The overall prevalence of CR isolates was 2.9% (111/3840). Based on the disc diffusion test, prevalence of resistance to carbapenems were doripenem (75%), imipenem (66.7%), and meropenem (58%). The highest measurable MIC levels (≥32 μg/mL) were observed in 56.8% of CR isolates with the nonfermenters, Pseudomonas aeruginosa (24.3%) and Acinetobacter species (18.9%), disproportionately represented. Phenotypic identification of carbapenamase activity occurred in 18.9% of the CR isolates by the modified Hodge test and 2.7% by Boronic acid disc synergy test; 21.6% exhibited carbapenemase production by both methods. All the CR isolates carried ESBL genes (blaTEM and blaSHV), whereas 23.4% were carriers of carbapenemase genes, of which 14.4% were blaNDM-1, 7.2% blaVIM-1, and 1.8% blaOXA-48. Phylogenetically, the CR isolates were diverse and showed limited relatedness to isolates from other geographical regions. [ABSTRACT FROM AUTHOR]

Background Healthcare-associated infections pose a major, yet often preventable risk to patient safety. Poor hand hygiene among healthcare personnel and unsanitary hospital environments may contribute to this risk in low-income settings. We aimed to describe hand hygiene behaviour and environmental contamination by season in a rural, sub-Saharan African hospital setting. Methods We conducted a concurrent triangulation mixed-methods study combining three types of data at a hospital in Madarounfa, Niger. Hand hygiene observations among healthcare personnel during two seasons contributed quantitative data describing hand hygiene frequency and its variability in relation to seasonal changes in caseload. Semistructured interviews with healthcare personnel contributed qualitative data on knowledge, attitudes and barriers to hand hygiene. Biweekly environmental samples evaluated microbial contamination from October 2016 to December 2017. Triangulation identified convergences, complements and contradictions across results. Results Hand hygiene compliance, or the proportion of actions (handrubbing or handwashing) performed out of all actions required, was low (11% during non-peak and 36% during peak caseload seasons). Interviews with healthcare personnel suggesting good general knowledge of hand hygiene contradicted the low hand hygiene compliance. However, compliance by healthcare activity was convergent with poor knowledge of precise hand hygiene steps and the motivation to prevent personal acquisition of infection identified during interviews. Contamination of environmental samples with gram-negative bacilli was high (45%), with the highest rates of contamination observed during the peak caseload season. Conclusion Low hand hygiene compliance coupled with high contamination rates of hospital environments may increase the risk of hospital-acquired infections in sub-Saharan African settings. [ABSTRACT FROM AUTHOR]

Relebactam, previously known as MK-7655, is currently being tested in combination with imipenem as a class A and class C β-lactamase inhibitor, including KPC from Klebsiella pneumoniae. The objective of the current study was to evaluate the activity of imipenem/relebactam against gram-negative bacilli. After applying exclusion and inclusion criteria, 72 articles with full texts that describe the prevalence of imipenem/relebactam resistance were chosen for the meta-analysis and systematic review. Articles published between January 2015 and February 2023 were surveyed. The systematic literature search was conducted in PubMed, Web of Science, Google Scholar, and Scopus. The pooled estimation of 282,621 sample isolates revealed that the prevalence rate of imipenem/relebactam resistance is roughly 14.6% (95% CI, 0.116%–0.182%). The findings of this analysis show that imipenem/relebactam resistance is rare in the majority of developed countries. Given that relebactam has proven to restore the activity of imipenem against current clinical isolates, further research into imipenem/relebactam is necessary. [ABSTRACT FROM AUTHOR]

Chromobacterium violaceum (C. violaceum) is a motile, gram-negative bacilli found in water and moist soil. Infections due to C. violaceum are uncommon but have a significant mortality rate (upto 80%) due to their tendency for haematogenous dissemination resulting in sepsis. The organism has been reported to cause skin and soft tissue infections, diarrhoea, bacteremia, and visceral abscess; Urinary Tract Infection (UTI) is rarely seen. Here, a 41-year-old male diabetic who presented with fever, altered sensorium and burning micturition caused by C.violaceum is presented. Initial investigations revealed an increased Random Blood Sugar (RBS) level, high anion gap metabolic acidosis with normal renal and liver function (except for hypoalbuminemia). Diabetic ketoacidosis, probable meningitis and urosepsis were considered as differential diagnosis. On culture of urine sample, C. violaceum was isolated which was susceptible to all the antibiotics tested except amikacin. Blood culture was reported as sterile. Patient was successfully treated with susceptible antibiotic (ciprofloxacin) and repeat culture of urine was also sterile. Early diagnosis and adequate treatment is necessary to reduce the risk of progression to fatal infection. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance (AMR) among gram-negative bacilli is a global health problem. Surveillance of AMR is required to advise on empirical antimicrobial therapy. This study aimed at evaluating the frequency and the AMR patterns of gram-negative isolates from patients treated in eight hospitals in Khartoum State, Sudan. Methods: A cross-sectional laboratory-based study was conducted over a 6 months period at the Microbiology Department, Soba University Hospital- Khartoum State, Sudan. All gram-negative isolates from blood, urine, wound, and sputum during the period of study were included. Identification and antimicrobial susceptibility testing were carried out for all isolates. Results: A total of 734 Gram-negative bacilli were isolated. Klebsiella pneumoniae (249 isolates, 34%) was the most frequently encountered one, followed by Pseudomonas aeruginosa (153 isolates, 21%), E.coli (123 isolates, 17%), Acinetobacter baumannii (75 isolates, 10%), Burkholderia cepacia (42 isolates, 6%), Proteus mirabilis and Proteus vulgaris (28 isolates, each, (4%) Enterobacter colecaes (28 isolates, 4%), Stenotrophomonas maltophilia (21 isolates, 2.8%), and other gram-negative bacilli (15 isolates, 2.2%) The analysis of the antimicrobial susceptibility patterns showed that 134 (22.3%) isolates were resistant to three or more classes of antibiotics, including cephalosporins, β-lactam–β-lactamase inhibitor, quinolones, aminoglycosides and carbapenems. Conclusion: This high level of resistance among gram-negative bacilli in Khartoum state hospitals is alarming. The local health authorities should be prompted to step up infection control programs and introduce the concept of antimicrobial stewardship in Khartoum State hospitals.

Abstract Background Sinks in patient rooms are associated with hospital-acquired infections. The aim of this study was to evaluate the effect of removal of sinks from the Intensive Care Unit (ICU) patient rooms and the introduction of ‘water-free’ patient care on gram-negative bacilli colonization rates. Methods We conducted a 2-year pre/post quasi-experimental study that compared monthly gram-negative bacilli colonization rates pre- and post-intervention using segmented regression analysis of interrupted time series data. Five ICUs of a tertiary care medical center were included. Participants were all patients of 18 years and older admitted to our ICUs for at least 48 h who also received selective digestive tract decontamination during the twelve month pre-intervention or the twelve month post-intervention period. The effect of sink removal and the introduction of ‘water-free’ patient care on colonization rates with gram-negative bacilli was evaluated. The main outcome of this study was the monthly colonization rate with gram-negative bacilli (GNB). Yeast colonization rates were used as a ‘negative control’. In addition, colonization rates were calculated for first positive culture results from cultures taken ≥3, ≥5, ≥7, ≥10 and ≥14 days after ICU-admission, rate ratios (RR) were calculated and differences tested with chi-squared tests. Results In the pre-intervention period, 1496 patients (9153 admission days) and in the post-intervention period 1444 patients (9044 admission days) were included. Segmented regression analysis showed that the intervention was followed by a statistically significant immediate reduction in GNB colonization in absence of a pre or post intervention trend in GNB colonization. The overall GNB colonization rate dropped from 26.3 to 21.6 GNB/1000 ICU admission days (colonization rate ratio 0.82; 95%CI 0.67–0.99; P = 0.02). The reduction in GNB colonization rate became more pronounced in patients with a longer ICU-Length of Stay (LOS): from a 1.22-fold reduction (≥2 days), to a 1.6-fold (≥5 days; P = 0.002), 2.5-fold (for ≥10 days; P

ABSTRACT We characterize by whole-plasmid-sequence (WPS) two-plasmid-borne blaOXA-58 obtained from Acinetobacter seifertii (Asp-1069) and A. baumannii (Acb-45063) clinical strains recovered 17 years apart from distinct Brazilian regions. Multilocus sequence type (MLST) analysis showed that the Asp-1069 and Acb-45063 strains belong to ST551 and ST15/CC15, respectively. WPS analysis demonstrated that blaOXA-58 was located in two distinct plasmids named pAs1069_a (24,672 bp/44 open reading frames [ORFs]) and pAb45063_b (19,808 bp/24 ORFs), which belong to the GR8/GR23 (repAci23) and GR4 (repAci4) incompatibility groups, respectively. The genetic environments surrounding blaOXA-58 revealed that it was flanked by two intact ISAba3 copies on pAb45063_b, which differed from pAs1069_a. In the latter, the upstream ISAba3 copy was truncated by insertion of ISAba825 element. Although Re27-specific recombination sites were found adjacent to ISAba3-blaOXA-58-ISAba3 arrangement on pAb45063_b, such structures were absent on pAs1069_a. The conserved ISAba125-araC1-lysE arrangement was disrupted by TnaphA6 harboring the aminoglycosides resistance gene aphA6 on pAs1069_a, while an IS26-blaTEM-1-aac(3)-IIa-IS26 genetic structure was found upstream from ISAba3-blaOXA-58-ISAba3 on pAb45063_b. Other two plasmids, pAb45063_a (183,767 bp/209 ORFs) and pAs1069_b (13,129 bp/14 ORFs), were also found in the OXA-58-producing Acinetobacter species strains, harboring the strA and strB genes and the sul2 gene, which confer resistance to streptomycin and sulfonamides, respectively. The plasmid-mediated virulence factors corresponding to genes tonB, spl, glmM, ppa, sulP, and map were found in both strains, as well distinct toxin-antitoxin system-encoding genes stbD and relE (pAs1069_a), brnT and brnA (pAb45063_b), and xreE (pAb45063_a). Although infrequently reported in Brazil, plasmid-borne blaOXA-58 showed a complex and diverse genetic backbone that confers stability in different Acinetobacter species that have been isolated from nosocomial settings over time. IMPORTANCE Although the blaOXA-58 gene has been infrequently described in Brazil, contrasting with other bordering South American countries, we verified the maintenance of this resistance determinant over time among carbapenem-resistant Acinetobacter species isolates, not only in nosocomial settings but also in the environment. In addition, to the best of our knowledge, this is the first study to have used WPS analysis to evaluate the genetic surroundings of blaOXA-58 in Brazil. Moreover, the A. seifertii and A. baumannii clinical strains evaluated in this study were recovered 17 years apart in hospitals located in distinct Brazilian geographic regions.

The typing of epidemic bacterial pathogens in hospitals relies on DNA-based, expensive, and time-consuming techniques, that are often limited to retrospective studies. However, the quick identification of epidemic pathogens in the routine of the microbiology laboratories would expedite infection control procedures that limit the contamination of new patients. IR Biotyper (Bruker Daltonics GmbH) is a new typing machine based on Fourier-transform infrared (FTIR) spectroscopy which generates spectra, aiming at typing the micro-organisms within 3 h. This technique discriminates the isolates by exploring the differences of the surface cell polysaccharides. In this work, we evaluated the ability of the FTIR spectroscopy to recognize Gram-negative bacilli clones responsible for hospital outbreaks. Isolates of Pseudomonas aeruginosa (n = 100), Klebsiella pneumoniae (n = 16), Enterobacter cloacae (n = 23), and Acinetobacter baumannii (n = 20) were typed by the reference methods Multi-Locus Sequence Typing (defining sequence types – STs) along with or without pulsed field gel electrophoresis (PFGE) (defining pulsotypes), and by FTIR spectroscopy. The congruence of FTIR spectroscopy clustering was compared to those of MLST and PFGE by Adjusted Rand index and Adjusted Wallace coefficient. We found that FTIR spectroscopy accurately clustered P. aeruginosa, K. pneumoniae, and E. cloacae isolates belonging to the same ST. The performance of the FTIR spectroscopy was slightly lower for A. baumannii. Furthermore, FTIR spectroscopy also correctly clustered P. aeruginosa isolates having a similar pulsotype. Overall, the IR Biotyper can quickly (in less than 3 h) detect the spread of clones of P. aeruginosa, K. pneumoniae, E. cloacae, and A. baumannii. The use of this technique by clinical microbiology laboratories may help to tackle the spread of epidemic clones by the quick implementation of infection control measures.

With increasing resistance to conventional antibiotic treatments, especially among gram-negative bacilli, the search for new antibiotics has become critical on a global scale. Among infections with multidrug-resistant bacteria is hospital-acquired pneumonia (HAP), which is nosocomial pneumonia in patients who have been hospitalized for more than 48 hours. HAP carries a high mortality rate and continues to be a challenge with regard to adequate treatment. The typical multidrug-resistant gram negatives found in HAP include Pseudomonas aeruginosa , Klebsiella pneumoniae , and Acinetobacter baumannii . Many new antibiotics have been studied and tested against these pathogens as possible solutions, and the search continues. Cefiderocol, a novel siderophore cephalosporin, is effective against these pathogens. Cefiderocol is an iron-chelating agent that makes use of iron pumps on the membrane of bacteria via a catechol moiety on the C3 side chain of the molecule. This allows for easy access into the cytoplasm, where it can inhibit peptidoglycan synthesis by binding to penicillin-binding proteins. Cefiderocol displays linear pharmacokinetics and is mainly excreted through the kidneys. It is well tolerated in healthy individuals but may need adjustments of dosage in patients with impaired renal function. Studies have shown that both healthy subjects and those with impaired renal function experienced some adverse effects, including nausea, diarrhea, abdominal pain, and increased creatinine kinase; however, these adverse effects were limited and experienced in placebo groups. It has demonstrated efficacy in treating infections caused by many multidrug-resistant gram-negative pathogens and has demonstrated high stability against many classes of b-lactamases. There have been multiple phase 3 trials, such as the CREDIBLE-CR trial and the APEKS-NP trial, that demonstrated efficacy in treated nosocomial pneumonia caused by multidrug-resistant gram negatives, such as carbapenem-resistant Acinetobacter baumannii , Klebsiella pneumoniae , and Pseudomonas aeruginosa , compared to the best available treatment. While clinical data remain limited, a few studies are showing clinical efficacy and few adverse effects. Cefiderocol demonstrated effectivity in treating multidrug-resistant gram-negative pneumonia in patients with multiple comorbidities, such as chronic kidney disease, chronic-obstructive pulmonary disease, and diabetes mellitus. Cefiderocol shows promise as a novel antimicrobial agent in treating multidrug-resistant gram-negative in HAP., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Plaisance et al.)

Background: Gram-negative bacilli are one of the most common causes of various infections in clinical. The emergence and global spread of multi-drug resistant gram-negative bacilli has become a major challenge in the global public health field., Methods: A total of 51,189 non-repetitive strains of gram-negative bacilli were isolated in clinical settings. The antimicrobial susceptibility testing was conducted by using the automated VITEK 2 compact system and the matched AST susceptibility test card, complemented by the disk diffusion method. The antimicrobial susceptibility results were interpreted by CLSI. Rates of MDR and XDR in Klebsiella pneumoniae , Acinetobacter baumannii , and Pseudomonas aeruginosa were investigated. Used the chi-square test to determine whether the antimicrobial resistance rates of four major gram-negative bacilli isolated from ICU and non-ICU department have statistical differences., Results: Escherichia coli (31.4%), Klebsiella spp. (21.2%), Acinetobacter spp. (13.8%), and P. aeruginosa (11.0%) were the most frequently isolated gram-negative bacilli. Escherichia coli was the top one organism isolated from urinary tract (68.4%), bloodstream (39.9%), body fluid (33.2%), wound and pus (37%), except for respiratory tract (8.8%). Whereas Acinetobacter baumannii and K. pneumoniae were the major isolated organisms from respiratory tract. Acinetobacter baumannii showed high resistance to fluoroquinolones, β-lactam/β-lactamase inhibitor combinations class, ceftazidime, cefepime, imipenem, and meropenem, the resistance rates reached more than 70%. Ceftazidime showed a lower resistance rate to E. coli than ceftriaxone. For E. coli , fluoroquinolones showed a high resistance rate (ciprofloxacin 61.36% and levofloxacin 53.97%), whereas amikacin, carbapenems exhibited a lower resistance rate fluctuating at 2%. Acinetobacter baumannii and K. pneumoniae showed rapid increases in carbapenem resistance whereas E. coli had the lowest resistance rate and remain stable at 2%. Acinetobacter baumannii exhibited the highest rate of MDR and XDR, reaching 60-80 and 45-55%, respectively. Compared to non-ICU departments, the resistance rates of four major gram-negative bacilli in the ICU department were much higher and the differences were statistically significant ( p < 0.05)., Conclusion: Amikacin, carbapenems, and piperacillin/tazobactam exhibited relatively high sensitivity, whereas fluoroquinolones showed high resistance rate whether they can be the first-line antimicrobials for empirical treatment of UTI should take more consideration. The gram-negative bacilli in ICU were more resistance than that in non-ICU. These findings are helpful for clinicians using antimicrobials reasonably., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shi and Xie.)

Background Ascitic fluid culture remains an essential step in the management of all patients with ascites, regardless of their presenting complaints. Diagnostic paracentesis should not be delayed or prevent timely administration of antibiotics, particularly in unstable patients. Hence, it is an essential part of the surveillance system of every hospital to perform ascitic fluid culture and assess the antibiotic susceptibility patterns of bacterial isolates. In view of this perspective, the present study was conducted at Chengalpattu Medical College Hospital, Tamil Nadu, India. Objective The aim of the study is to determine the bacterial isolates of ascitic fluid samples and study their antibiotic susceptibility patterns. Materials and methods Ascitic fluids received in the central laboratory at the Department of Microbiology from various departments were included in this study. Preliminary identification of isolates was performed by direct Gram staining, acid-fast staining, and motility testing by the hanging drop method. Within one hour of receiving the samples, they were plated onto blood agar and MacConkey agar media and incubated for 18-24 hours at 37°C for isolation. Growth was checked, and species identification was done based on conventional methods. Antibiotic susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Results In this study, a total of 100 ascitic fluid samples were collected, of which only eight (8%) showed growth. Among the eight isolates, six (75%) were Gram-negative bacilli (GNB). Four (66.66%) of the six GNB were  Klebsiella spp., while the remaining two (33.33%) were Escherichia coli . Both Gram-positive cocci were  Staphylococcus aureus . All the GNB isolates were susceptible to meropenem, piperacillin-tazobactam, and ceftriaxone, with varying susceptibilities to other drugs. Both Gram-positive isolates were found to be methicillin-sensitive Staphylococcus aureus. Conclusion GNB were the predominant organisms in cases of ascitic fluid infection, and they showed 100% susceptibility to carbapenem drugs (especially meropenem), piperacillin-tazobactam, and ceftriaxone. All these drugs can be kept in reserve for serious infections. Amikacin and gentamicin showed promising susceptibility. These drugs can be started empirically with patients on admission before performing culture. Drug adjustments may be later made based on culture reports., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Pachiyappan et al.)

Introduction: Sepsis is a systemic, host response to infection that progresses from sepsis to severe sepsis to septic shock. Severe sepsis carries significant morbidity and mortality. In the presence of individual risk factors such as old age, diabetes mellitus, chronic liver and renal disease, the death rate remains high despite treatment with antimicrobial agents. Aim: To determine the factors associated with severe sepsis or septic shock and to identify the factors influencing the mortality among patients with gram-negative bacteraemia. Materials and Methods: In this observational cohort study, 219 patients with gram-negative bacteraemia were screened for the presence of sepsis, severe sepsis and septic shock and detailed characteristics of the patients were analysed using independent sample t-test, chi-square test and logistic regression. Results: Among 219 patients with gram-negative bacteraemia, 43 (19.6%) were classified as severe sepsis, 69 (31.5%) as septic shock and the remaining 107 (48.9%) as only sepsis according to clinical criteria. Diabetes mellitus (p-value=0.006), chronic liver disease (p-value=0.001), presence of urinary catheter (p-value4 was significant (p-value

Due to the significant increase in antimicrobial resistance in Gram-negative bacilli (GNB), development of non-antimicrobial therapeutic alternatives, which can be used together with the few and non-optimal available antimicrobial agents such as colistin, has become an urgent need. In this context, dysregulation of the bacterial cell wall could be a therapeutic adjuvant to the activity of colistin. The aim of this study was to analyse the activity of oxyclozanide, an anthelmintic drug, in combination with colistin against colistin-susceptible (Col-S) and colistin-resistant (Col-R) GNB. Three Col-S reference strains and 13 clinical isolates (1 Col-S, 12 Col-R) of Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae were studied. Microdilution assays and time–kill curves were performed to examine the activity of oxyclozanide in combination with colistin. The outer membrane protein (OMP) profile, membrane permeability and cell wall structure of Col-S and Col-R A. baumannii, P. aeruginosa and K. pneumoniae in the presence of oxyclozanide were assessed by SDS-PAGE, fluorescence microscopy and transmission electron microscopy, respectively. Oxyclozanide in combination with colistin increased the activity of colistin against Col-S and Col-R A. baumannii, P. aeruginosa and K. pneumoniae. Time–kill curves showed synergistic activity between oxyclozanide and colistin against these bacterial isolates. Moreover, Col-R A. baumannii, P. aeruginosa and K. pneumoniae in the presence of oxyclozanide presented greater permeability and disruption of their cell wall than Col-S strains, without modification of their OMP profile. These data suggest that combination of oxyclozanide and colistin may be a new alternative for the treatment of Col-R GNB infections. [ABSTRACT FROM AUTHOR]

In 2017, the Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing approved the use of iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB) prepared with Chelex® 100 resin (Bio-Rad Laboratories, Hercules, CA) to determine MICs for cefiderocol. The current study examined the reproducibility of cefiderocol MICs generated for 19 clinical isolates of Gram-negative bacilli, with CAMHB produced by three manufacturers; each of the 19 isolates was tested for 10 replicates in ID-CAMHB from each manufacturer. When analyzed by individual media lot, greater than 95% of MIC results were within ± one doubling-dilution of the mode for each of the 19 isolates tested. The remaining 5.0% of MIC results were within ± two doubling-dilutions of the modal MIC. For all media lots combined, 92.2% of MIC results were within ± one doubling-dilution of the modal MIC for each isolate, 99.8% were within ± two doubling-dilutions and 100% were within three doubling-dilutions. [ABSTRACT FROM AUTHOR]

Background: Ventilator-Associated Pneumonia (VAP) occurs in hospitalized patients who have undergone intubation and mechanical ventilation for more than 48 hours. Patients referred to the Intensive Care Unit (ICU) are also affected by VAP due to specific conditions, especially by Gram-negative pathogens with advanced drug resistance. In this study, the pattern of antibiotic resistance of gram negative bacteria isolated from tracheal culture of VAP patients was investigated in ICU. Materials and Methods: In this cross-sectional study, tracheal samples were collected from VAP patients admitted in the hospital's ICU from March 2017- February 2018. After isolation, bacterial isolates were identified using biochemical tests. Then, antimicrobial resistance pattern of these isolates was investigated using standard disc diffusion and E-test methods. Multiplex PCR were used to detect the blaOXA-23-like, blaOXA-51-like, blaOXA-24-like, and blaOXA-58-like genes among Acinetobacter baumannii (A. baumannii) isolates. Results: A total of 29 bacterial isolates were isolated from ICU patients, which were A. baumannii, Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumoniae) and candida spp, with prevalence of 38, 27.5, 13.8, and 20.7%, respectively. Antibiotic susceptibility test of isolates indicated that almost all isolates showed Multi-Drug Resistance (MDR) pattern. The A. baumannii isolates were resistant to ciprofloxacin and piperacillin-tazobactam, but ampicillin-sulbactam and colistin had better results. Ciprofloxacin, meropenem and colistin were effective against P. aeruginosa isolates, but other antibiotics were less effective and Colistin, Levofloxacin (LVX) and Piperacilin/Tazobactam were the best antibiotics that were effective on the isolates of K. pneumonia. Conclusion: According to the present study, high resistance to most antibiotics in gram negative bacilli showed that antibiotic therapy should be based on the type of bacteria isolated by tracheal culture and, as far as possible, combination therapies should be used to maximize the coverage of other possible pathogens, and antibiotic resistance in ICU. [ABSTRACT FROM AUTHOR]

The article presents a study on the status of development and approval of systemic antibiotics in the U.S. as of late 2018. Topics discussed include a review of published literature and on-line clinical registry at www.clinicaltrials.gov, drugs in clinical development for treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacilli (GNB), and initiatives from the Infectious Disease Society of America (ISDA).

The typing of epidemic bacterial pathogens in hospitals relies on DNA-based, expensive, and time-consuming techniques, that are often limited to retrospective studies. However, the quick identification of epidemic pathogens in the routine of the microbiology laboratories would expedite infection control procedures that limit the contamination of new patients. IR Biotyper (Bruker Daltonics GmbH) is a new typing machine based on Fourier-transform infrared (FTIR) spectroscopy which generates spectra, aiming at typing the micro-organisms within 3 h. This technique discriminates the isolates by exploring the differences of the surface cell polysaccharides. In this work, we evaluated the ability of the FTIR spectroscopy to recognize Gram-negative bacilli clones responsible for hospital outbreaks. Isolates of Pseudomonas aeruginosa (n = 100), Klebsiella pneumoniae (n = 16), Enterobacter cloacae (n = 23), and Acinetobacter baumannii (n = 20) were typed by the reference methods Multi-Locus Sequence Typing (defining sequence types – STs) along with or without pulsed field gel electrophoresis (PFGE) (defining pulsotypes), and by FTIR spectroscopy. The congruence of FTIR spectroscopy clustering was compared to those of MLST and PFGE by Adjusted Rand index and Adjusted Wallace coefficient. We found that FTIR spectroscopy accurately clustered P. aeruginosa , K. pneumoniae , and E. cloacae isolates belonging to the same ST. The performance of the FTIR spectroscopy was slightly lower for A. baumannii. Furthermore, FTIR spectroscopy also correctly clustered P. aeruginosa isolates having a similar pulsotype. Overall, the IR Biotyper can quickly (in less than 3 h) detect the spread of clones of P. aeruginosa , K. pneumoniae , E. cloacae , and A. baumannii. The use of this technique by clinical microbiology laboratories may help to tackle the spread of epidemic clones by the quick implementation of infection control measures. [ABSTRACT FROM AUTHOR]

To standardize the methodology for conducting direct antimicrobial susceptibility testing (AST) of Enterobacterales and Pseudomonas aeruginosa causing bacteremia from positive blood culture pellets. Two methods for processing positive blood cultures with Enterobacterales and P. aeruginosa were compared: a conventional method for identification and AST versus a direct method obtaining a pellet for both matrix-assisted laser desorption/ionization–time of flight (MALDI-TOF) identification and direct AST. A total of 157 (145 Enterobacterales, 12 P. aeruginosa) positive blood cultures were included. Microorganism identification showed 100% concordance between both methods at species and genus level. Definitive AST results were obtained 24 h earlier with the rapid method than the conventional one (p < 0.001). Of the 2814 MICs generated, there were discrepancies with respect to the conventional method in 47 (1.7%), 0.3% being very major (VME) and 1.3% major (ME) errors. Better results for AST were obtained when colony counts with the pellet were ≥ 105 cfu/ml. The essential agreement (EA) for antibiotics tested in Enterobacterales was at least 97%, except for ampicillin (95%). Regardless of colony count, the greatest discrepancies were observed for first/s-generation cephalosporins and aminoglycosides. In P. aeruginosa, EA was at least 92%, except for piperacillin-tazobactam (84%) and cefepime (76%). No VME occurred except for ceftazidime (8%). ME occurred in piperacillin/tazobactam (16%), ticarcillin, ceftazidime, tobramycin, amikacin, and colistin (8% each). Direct use of the blood culture pellet permits fast AST in bacteremia of Enterobacterales, enabling the clinicians to perform an early treatment adjustment. However, for Pseudomonas aeruginosa, the data needs expanding to improve the reliability of this technique. [ABSTRACT FROM AUTHOR]

New Delhi metallo-β-lactamase (NDM)-producing bacteria have been identified at a worrying rate in Brazil since 2013. Owing to the need to understand the extent of their spread, this study reports the dissemination of blaNDM in different species of Gram-negative bacilli in different regions and states of Brazil. A total of 81 isolates from nine states were studied, including 11 species. All isolates carried blaNDM-1 variant and were considered multidrug resistant. Colistin and amikacin were the agents with higher activity compared with the other drugs tested. The findings indicate that the NDM-1 enzyme is already widespread in the country. [ABSTRACT FROM AUTHOR]

Highlights • Cefiderocol is an investigational parenteral siderophore cephalosporin • Cefiderocol MICs were ≤4 µg/mL for 99.4% of 8954 isolates of Gram-negative bacilli • 99.6% of meropenem-non-susceptible Enterobacteriaceae had cefiderocol MICs ≤4 µg/mL • 99.7% of meropenem-non-susceptible P. aeruginosa had cefiderocol MICs ≤4 µg/mL • 96.1% of meropenem-non-susceptible Acinetobacter spp. had cefiderocol MICs ≤4 µg/mL ABSTRACT Cefiderocol (S-649266) is a parenteral siderophore cephalosporin in phase III of clinical development. In this study, we determined the in vitro susceptibility to cefiderocol and comparators of a 2015-2016 collection of 8954 clinical isolates of Gram-negative bacilli (GNB), provided by 100 clinical laboratories in North America and Europe, using the Clinical and Laboratory Standards Institute broth microdilution method. Iron-depleted cation-adjusted Mueller-Hinton broth was used to test cefiderocol. The concentration of cefiderocol inhibiting 90% of isolates (MIC 90) was 0.5 mg/L (North America; n =2470) and 1 mg/L (Europe; n =3,543) for Enterobacteriaceae, 0.5 mg/L (North America; n =619) and 0.5 mg/L (Europe; n =921) for Pseudomonas aeruginosa , 1 mg/L (North America; n =308) and 2 mg/L (Europe; n =664) for Acinetobacter spp., 0.5 mg/L (North America; n =165) and 0.25 mg/L (Europe; n =175) for Stenotrophomonas maltophilia , and 0.12 mg/L (North America; n =40) and 0.5 mg/L (Europe; n =49) for Burkholderia cepacia complex spp. Cefiderocol MICs were ≤4 mg/L for 99.9% (6005/6013) of Enterobacteriaceae, 99.9% (1539/1540) of P. aeruginosa , 96.4% (937/972) of Acinetobacter spp., 99.4% (338/340) of S. maltophilia , and 94.4% (84/89) of Burkholderia cepacia complex spp. isolates tested. Against meropenem-non-susceptible isolates, MICs to cefiderocol were ≤4 mg/L for 99.6% (245/246) of Enterobacteriaceae, 99.7% (394/395) of P. aeruginosa , 96.1% (540/562) of Acinetobacter spp., and 87.1% (27/31) of B. cepacia complex spp. We conclude that cefiderocol demonstrated potent in vitro activity (MIC ≤4 mg/L) against the majority (99.4%, 8903/8954) of clinical isolates of GNB in a recent (2015-2016), multi-continent collection, including carbapenem-non-susceptible isolates. [ABSTRACT FROM AUTHOR]

Highlights • Epithelial lining fluid (ELF) penetration is variable following systemic antibiotic administration • ELF concentrations of nebulised antibiotics exceed that possible with systemic administration of antibiotics • The pharmacokinetic/pharmacodynamic targets in the ELF have not been described Abstract Background Knowledge of antibiotic concentrations achievable in the epithelial lining fluid (ELF) will help guide antibiotic dosing for treating patients with Gram-negative bacillary ventilator-associated pneumonia (VAP). Objective To compare: (1) the ELF:serum penetration ratio of antibiotics in patients with pneumonia, including VAP, with that in healthy study participants; and (2) the ELF and/or tracheal aspirate antibiotic concentrations following intravenous and nebuliser delivery. Methods Web of Science, EMBASE and PubMed databases were searched and a systematic review undertaken. Results Fifty-two studies were identified. ELF penetration ratios for aminoglycosides and most β-lactam antibiotics administered intravenously were between 0.12 and 0.57, whereas intravenous colistin may be undetectable in the ELF. In contrast, estimated mean fluoroquinolone ELF penetration ratios of up to 1.31 were achieved. Importantly, ELF penetration ratios appear reduced in critically ill patients with pneumonia compared with in healthy volunteers receiving intravenous ceftazidime, levofloxacin and fosfomycin; thus, dose adjustment is likely to be required in critically ill patients. In contrast to the systemic administration route, nebulisation of antibiotics achieves high ELF concentrations. Nebulised 400 mg twice-daily amikacin resulted in a median peak ELF steady-state concentration of 976.01 mg/L (interquartile range 410.3–2563.1 mg/L). Similarly, nebulised 1 million international units of colistin resulted in a peak ELF concentration of 6.73 mg/L (interquartile range 4.80–10.10 mg/L). Conclusion Further pharmacokinetic studies investigating the mechanisms for ELF penetration in infected patients and healthy controls are needed to guide antibiotic dosing in VAP and to determine the potential benefits of nebulised therapy. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Gold nanorods are immobilized on Ti surface by the LBL self-assembly method. • The Ti-GNR surface exhibited recyclable photothermal antibacterial activity. • The Ti-GNR surface shows better antibacterial effect against Gram-negative bacilli. • The Ti-GNR surface possessed weak photothermal cytotoxicity. Abstract Titanium and its alloys are widely used in many clinical applications, but implant-associated infection may lead to implant failure. Because of the increasing concern about antibiotic resistant pathogen, photothermal therapy (PTT) as a new treatment strategy has received considerable attention. In this work, gold nanorods (GNRs) photoexcited by the near-infrared (NIR) light were immobilized on Ti surface by electrostatic surface self-assembly technique. Field emission scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) were used to explore the morphology and composition of the GNRs-modified surface. The photothermal temperature of the immobilized GNRs was measured by an infrared thermal imaging system in real time. In vitro study reveal that the prepared GNRs-modified surface exhibits antibacterial activity against four kinds of bacterial strains including both Gram-negative bacilli (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive cocci (Staphylococcus aureus and Staphylococcus epidermidis) under the irradiation of 808 nm laser. Besides, the antibacterial efficiency of the GNRs-modified surface could keep stable after multiple laser exposure. It should be noted that the GNRs-modified surface shows better antibacterial effect against Gram-negative bacilli compared to Gram-positive cocci. Moreover, the GNRs-modified surface has no obvious adverse effect to the osteoblast precursor cells under NIR irradiation. These data demonstrate that the GNRs-modified surface with negligible cytotoxicity and recyclable antibacterial effect provides a favorable model for the translation of photothermal therapy to the clinical application. [ABSTRACT FROM AUTHOR]

Introduction: Sepsis is a systemic, host response to infection that progresses from sepsis to severe sepsis to septic shock. Severe sepsis carries significant morbidity and mortality. In the presence of individual risk factors such as old age, diabetes mellitus, chronic liver and renal disease, the death rate remains high despite treatment with antimicrobial agents. Aim: To determine the factors associated with severe sepsis or septic shock and to identify the factors influencing the mortality among patients with gram-negative bacteraemia. Materials and Methods: In this observational cohort study, 219 patients with gram-negative bacteraemia were screened for the presence of sepsis, severe sepsis and septic shock and detailed characteristics of the patients were analysed using independent sample t-test, chi-square test and logistic regression. Results: Among 219 patients with gram-negative bacteraemia, 43 (19.6%) were as classified as severe sepsis, 69 (31.5%) as septic shock and the remaining 107 (48.9%) as only sepsis according to clinical criteria. Diabetes mellitus (p-value=0.006), chronic liver disease (p-value=0.001), presence of urinary catheter (p-value<0.001) and organisms other than E. coli (p-value=0.036) had a significant association with severe sepsis. Mortality was observed in 82 (73.3%) patients with severe sepsis and septic shock. The factors that predicted mortality among patients with gram-negative bacteraemia were age =65 years, chronic liver disease, indwelling urinary catheter, endotracheal and nasogastric tube, central venous access, organisms other than E. coli, respiratory and abdominal sources of infection. The mean Pitt bacteraemia score of >4 was significant (p-value <0.001) for development of severe sepsis and septic shock and mortality was higher in those with high scores. (p-value <0.0001). Conclusion: The present findings suggest that diabetes mellitus, chronic liver disease, indwelling urinary catheter and organisms other than E. coli are important risk factors for the development of severe sepsis or septic shock. Patients with higher Pitt bacteraemia score may have higher risk of death. [ABSTRACT FROM AUTHOR]

Highlights • 5000 fecal survey samples from inpatients prospectively and consecutively collected between July 1 and December 30, 2013. • Different genetic elements detected: integrons, insertion sequence common region 1 (IS CR1), complex class 1 integrons. • 389 carbapenem-non-susceptible strains from 5000 fecal specimens. • One novel gene cassette array was found in 205 class 1 integron–positive isolates. • Two different previously unreported complex class 1 integron-positive strains were isolated. Abstract The integrons and insertion sequence common region 1 (IS CR1) of 329 carbapenem-non-susceptible Gram-negative bacilli, excluding 60 Stenotrophomonas maltophilia strains, in fecal specimens from 5000 patients in southern China were studied. A total of 205 (62.3%) class 1 integron-positive strains and 126 (61.5%) gene-cassette-positive strains were detected, and 44 types of gene-cassette arrays were found, including 8 types described for the first time in the corresponding species and one gene cassette originally detected in integrons, a putative helicase. A total of 9 types of 21 IS CR1 -linked resistance gene regions in 35 IS CR 1-positive bacilli and 2 previously unreported types of complex class 1 integrons were detected. All strains were extensively drug-resistant. Class 1 integrons and IS CR1 were widely disseminated and these structures carried various resistance genes, which were closely associated with mechanisms of multidrug resistance, including carbapenem resistance. [ABSTRACT FROM AUTHOR]

• Antibiotic choices should cure the index infection and lower post-treatment resistant infections. • Aminoglycosides are frequently added to β-lactams in the treatment of sepsis/septic shock. • Propensity score and competing risk analyses were used to assess subsequent resistant infections. • Addition of aminoglycosides protects against recurrence with multidrug-resistant Gram-negative bacilli. • The treatment effect is larger in patients aged ≤65 years and with haematological malignancies. Aminoglycosides and β-lactams have been recommended for treatment of sepsis/septic shock despite a lack of mortality benefit. Previous studies have examined resistance emergence for the same bacterial isolate using old dosing regimens and during a narrow follow-up window. We hypothesised that combination regimens employing aminoglycosides will decrease the cumulative incidence of infections due to multidrug-resistant (MDR) Gram-negative bacilli (GNB) compared with β-lactams alone. All adult patients admitted to Barnes Jewish Hospital between 2010 and 2017 with a diagnosis of sepsis/septic shock were included in this retrospective cohort study. Patients were divided into two treatment groups, with and without aminoglycosides. Patient demographics, severity of presentation, administered antibiotics, follow-up cultures with susceptibility results for a period of 4–60 days, and mortality were extracted. After propensity score matching, a Fine–Gray subdistribution proportional hazards model summarised the estimated incidence of subsequent infections with MDR-GNB in the presence of all-cause death as a competing risk. A total of 10 212 septic patients were included, with 1996 (19.5%) treated with at least two antimicrobials including one aminoglycoside. After propensity score matching, the cumulative incidence of MDR-GNB infections between 4–60 days was lower in the combination group (incidence at 60 days 0.073, 95% CI 0.062–0.085) versus patients not receiving aminoglycosides (0.116, 95% CI 0.102–0.130). Patients aged ≤65 years and with haematological malignancies had a larger treatment effect in subgroup analyses. Addition of aminoglycosides to β-lactams may protect against subsequent infections due to MDR-GNB in patients with sepsis/septic shock. [ABSTRACT FROM AUTHOR]

Class 1 and 2 integrons are considered the paradigm of multidrug resistant (MDR) integrons. Although class 1 integrons have been found statistically associated to Enterobacteriaceae MDR isolates, this type of study has not been conducted for class 2 integrons. and 3 species that were found that harbored more than 20% of class 2 integrons in clinical isolates, were selected to determine the role of intI2 as MDR marker. A total of 234 MDR/191 susceptible non-epidemiologically related isolates were analyzed. Seventy-four intI2 genes were found by PCR and sequencing. An intI2 relationship with MDR phenotypes in Acinetobacter baumannii and Enterobacter cloacae was found. No statistical association was identified with MDR E. coli and Helicobacter pylori isolates. In other words, the likelihood of finding intI2 is the same in susceptible and in MDR E. coli and H. pylori strains, suggesting a particular affinity between the mobile element Tn7 and some species. The use of intI2 as MDR marker was species-dependent, with fluctuating epidemiology at geographical and temporal gradients. The use of intI2 as MDR marker is advisable in A. baumannii, a species that can reach high frequencies of this genetic element.

Background: Nosocomial infections are considered as health issues that affect developed and poor countries. These infections can be transmitted to patients through hospital environment and equipments. The aim of this study was to evaluate the prevalence of Gram-negative bacilli in the environment and the equipments of hospitals in the East of Golestan province in 2015. Methods: In this study, 770 samples were collected using sterile swabs from the environment and equipments which were in use in different units of six teaching hospitals located in the East of Golestan province. The collected samples were then identified by standard biochemical tests. Results: Of the total samples, 249 samples (32.33%) were contaminated with Gram-negative bacilli with the most number of contaminations were Enterobacter aerogenes (37.75%) at the Department of Surgery (18.07%). Among the medical equipments and surfaces, the highest level of contamination was observed in laryngoscope and its blades (10.44%), suctions (7.23%), and EKG sensors and monitoring connectors (7.23%). Telephone handset (5.22%) and patients’ bed (5.22%) had the highest rate of contamination with Gram-negative bacilli in the non-medical equipments. Conclusion: The results of the present study shows that Gram-negative bacilli contamination rates are considerable in hospitals in East of the Golestan province. Thus, hand washing, disinfecting, sterilizing medical equipment and generally compliance with the standards in this field are of great importance.

This study reports the simplified carbapenem inactivation method (sCIM) to detect carbapenemase-producing gram-negative bacilli in a simple and accurate manner. This method is based on the modified carbapenem inactivation method (mCIM) with the improvement of experimental procedures. Instead of incubating the antibiotic disk in the organism culture media, the organism to be tested was smeared directly onto the antibiotic disk in the sCIM. For evaluating the sensitivity and specificity of the method, a total of 196 Enterobacteriaceae, 73 Acinetobacter baumannii, and 158 Pseudomonas aeruginosa isolates were collected. Polymerase chain reaction (PCR) was used to detect the carbapenemase genes. Phenotypic evaluations were performed using both the sCIM and the mCIM. PCR results showed that, of the 196 Enterobacteriaceae strains, 147 expressed the carbapenemase genes blaKPC−2 (58.5%), blaIMP−4 (21.8%), blaIMP−2 (2.0%), blaVIM−1 (6.1%), blaNDM−1 (10.2%), and blaOXA−48 (1.4%). sCIM results had high concordance with PCR results (99.5%) and mCIM results (100%) with the exception of one Klebsiella pneumoniae strain, which had an minimal inhibitory concentration (MIC) for imipenem of 0.25 mg/L. PCR demonstrated that 53 of the 73 A. baumannii isolates expressed the carbapenemase genes blaOXA−23 (98.1%) and blaVIM−2 (1.8%). sCIM and PCR results corresponded but all A. baumannii isolates were carbapenemase negative by the mCIM. PCR demonstrated that 25 of the 158 P. aeruginosa isolates expressed carbapenemase genes blaVIM−1 (52%), blaVIM−2 (8%), blaVIM−4 (36%), and blaIMP−4 (4%). sCIM results had high concordance with PCR results (100%) and the mCIM results (99.4%) with the exception of one P. aeruginosa isolate that expressed the blaVIM−4 gene. The sCIM offers specificity and sensitivity comparable to PCR but has the advantage of being more user-friendly. This method is suitable for routine use in most clinical microbiology laboratories for the detection of carbapenemase-producing gram-negative bacilli.

Background: The emergence and spread of multidrug-resistant Gram-negative bacilliin burn wound infections related to biofilm formation, which lend to challenge in treatment with conventional antibiotics andprompting to search for novel antimicrobial agents to control the infections.Silver nanoparticles (AgNPs) have wide spectrum biological properties with different mechanisms of action and less toxicity towards human cells. Objective:The goal of this study was to evaluated the anti-bacterial and anti-biofilm activities of AgNPs alone and in combination with aminoglycoside (Amikacin) and β-lactam (Ampicillin) antibiotics against multidrug resistant Gram-negative bacilli (Pseudomonas aeruginosa, Escherichia coli, klebsiellapneumoniae) isolated from burn wound infections. Type of the study: Cross –sectional study. Methods: 70 clinical isolates of GNBtested for susceptibility tests by disk diffusion method against 10 antibiotics. The minimum inhibitory concentrations (MICs) of AgNPs and antibiotics were carried out according to the standard broth microdilution method, while synergistic interactions were evaluated by time kill-kinetic assays. Calgary method was applied for anti-biofilm activity. Results:Pseudomonas aeruginosa represented the majority of GNBisolated from burn wound infections 34 (48.5 %)followed by Klebsiella pneumonia 21 (30 %) and Escherichia coli 15 (21.5 %). Silver nanoparticles showed remarkable antibacterial activity against GNB that isolated from burn wound infections with the MICs between 25- 75 µg/ml. Aztreonam, amikacin and cefepime were the most effective antimicrobial drugagainst GNB isolates.Synergistic bactericidal effects were observed in two-drug combinations of AgNPswith broad-spectrum aminoglycoside (Amikacin) and β-lactam (Ampicillin) antibiotics against multidrug resistant GNB. In addition,AgNPsalone or in combination with ampicillin inhibited biofilm activity about 60 % – 75 % ofGNB,while combination of AgNPs withamikacin exhibited a powerful anti-biofilm activity and inhibition biofilm formation by 75% to 80%. Conclusion: The results confirmed a synergistic bactericidal effects and significant enhancing of anti-biofilm activity of AgNPs in combination with antibiotics (amikacin and ampicillin) against multidrug resistant GNB isolated from burn wound infections. These data suggest that AgNPs could beapplied as nanodrug for treatment of burn wound infections

Bartonella spp. are Gram-negative haemotropic bacteria transmitted by arthropod vectors. They are considered as important aetiologic agents of Blood Culture Negative Endocarditis (BCNE). The diagnosis of Bartonella endocarditis is often challenging because of its non-specific clinical presentation and difficulty in isolating the microorganism in culture using standard microbiological techniques as it is an intracellular bacterium. A combination of serological and molecular methods will aid in a comprehensive diagnosis of this condition. This study reports a series of four Bartonella endocarditis cases diagnosed in Chennai, Tamil Nadu, India. All of them were known Rheumatic Heart Disease (RHD) patients. The common valves affected in the patients were mitral and aortic valves. Three out of four cases showed presence of valvular vegetation in echocardiogram. One patient had a history of close contact with cats. Specific real time Polymerase Chain Reaction (PCR) targeting 16S-23S rRNA spacer region of Bartonella spp. was positive in three cases. Serology using Indirect Immunofluorescence Assay (IFA) was positive in one case. Western blot test was performed on serum samples of all four cases and Bartonella henselae was identified as the aetiological agent in one case. Extra cardiac complications were observed in three cases. Antibiotic treatment was successful in three out of four cases. One patient died due to acute renal failure. [ABSTRACT FROM AUTHOR]

Objective: Knowledge about the etiology of community-acquired pneumonia (CAP) is essential for adequate management. Presently, few studies about CAP are available from Southeast Asia. This study aimed to investigate the etiology, severity, and outcome of CAP in the most populous Southeast Asia country, Indonesia. Methods: From October 2007 to April 2009, adult patients admitted with CAP to two hospitals in Semarang, Indonesia, were included to detect the etiology of CAP using a full range of diagnostic methods. The severity of disease was classified according to the Pneumonia Severity Index (PSI). The outcome was assessed as 30-day mortality. Results: In total, 148 consecutive patients with CAP were included. Influenza virus (18%), Klebsiella pneumoniae (14%), and Streptococcus pneumoniae (13%) were the most common agents identified. Other Gram-negative bacilli, Mycobacterium tuberculosis, Chlamydia pneumoniae each accounted for 5%. The bacteria presented wild type antibiotic susceptibility profiles. Forty-four percent of subjects were high-risk patients (PSI class IV-V). The mortality rate (30%) was significantly associated with disease severity score (P

We describe the case of a 67-year-old African American woman with multiple medical problems who presented with septic shock resulting from Sphingobacterium multivorum bacteraemia. S. multivorum, a Gram-negative bacillus, is ubiquitous in nature and is rarely involved in human infections. However, it is intrinsically resistant to many commonly administered antibiotics and can be a life-threatening microorganism.

Background: Relebactam, previously known as MK-7655, is currently being tested in combination with imipenem as a class A and class C β-lactamase inhibitor, including KPC from Klebsiella pneumoniae ., Objective: The objective of the current study was to evaluate the activity of imipenem/relebactam against gram-negative bacilli., Methods: After applying exclusion and inclusion criteria, 72 articles with full texts that describe the prevalence of imipenem/relebactam resistance were chosen for the meta-analysis and systematic review. Articles published between January 2015 and February 2023 were surveyed. The systematic literature search was conducted in PubMed, Web of Science, Google Scholar, and Scopus., Results: The pooled estimation of 282,621 sample isolates revealed that the prevalence rate of imipenem/relebactam resistance is roughly 14.6% (95% CI, 0.116%-0.182%)., Conclusions: The findings of this analysis show that imipenem/relebactam resistance is rare in the majority of developed countries. Given that relebactam has proven to restore the activity of imipenem against current clinical isolates, further research into imipenem/relebactam is necessary., Competing Interests: The authors have indicated that they have no conflicts of interest regarding the content of this article., (© 2023 The Author(s).)

Background: The aim of this study was to determine the differences in the incidence, epidemiology, clinical characteristics and risk factors of infections in living donor kidney transplant recipients using robotic-assisted kidney transplantation (RAKT) and open approach., Methods: We conducted a retrospective observational study from January 2016 to December 2019. For the risk factor analysis, a matched case-control study (1:1 ratio) was performed (robotic vs open). Control subjects were matched for living donor and time of transplantation. The data included de novo immunosuppressive regimen, delayed graft function, urological complications, acute allograft rejection and incidence, clinical features, microbiological findings and outcomes of infections., Results: Ninety-four RAKT and 84 controls were included. There were no differences between groups in terms of age, gender, BMI, median days of hospitalization, immunosuppressive regimen, need for surgical urologic procedures post-transplantation, presence of urinary leak or acute allograft rejection. Thirty-five percent of all recipients analyzed presented an infection, mostly asymptomatic bacteriuria (49%), symptomatic urinary tract infection (31%) and surgical site infection (10%). Pseudomonas aeruginosa was the most frequent isolated microorganism in 67%, followed by E. coli (20%), Enterococcus faecalis (17%) and Klebsiella pneumoniae (10%). Eight percent of the microorganisms were multidrug resistant. The open kidney transplantation group presented more infections compared to RAKT (43 vs 27%, p = 0.04). After multivariate analysis, need for surgical urologic procedure post-transplantation (OR 6.2, 95% CI 1.1-35), BMI ≥ 30 (OR 3.6, 95% CI 1.5-9) and acute allograft rejection (OR 3.2, 95% CI 1.2-8.5) were associated with infection, whereas RAKT (OR 0.5, 95% CI 0.2-0.9) and the use of JJ catheter (OR 0.36, 95% CI 0.17-0.72) were protective factors., Conclusions: Infection is a frequent event in patients receiving a living donor kidney transplant. Acute allograft rejection, need for surgical urologic procedure post-transplantation and BMI were associated with infection, whereas robotic surgery was a protective factor in living donor kidney transplantation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The spread of multidrug-resistant bacteria, particularly carbapenem-resistant Gram-negative bacilli (CR-GNB), has become a serious challenge for clinicians due to limited therapeutic options. The aim of the study was to investigate the prevalence of carbapenemase production among clinical isolates recovered from 352 samples collected in Tebessa hospital, Algeria., Methodology: Bacterial isolates were identified by 16S RNA gene sequencing and susceptibility to antibiotics was determined by disk diffusion method. Carbapenem-resistant isolates were screened for carbapenemase production using modified carba Nordmann-Poirel test, modified Hodge test and imipenem-EDTA combined disc test. Extended-spectrum β-lactamases (ESBL) were detected using double-disk synergy test. Molecular characterization of carbapenemases and ESBL genes was performed by polymerase chain reaction (PCR) and sequencing., Results: A total of 85 Gram-negative bacilli isolates were recovered mainly from urine samples and were identified as: Klebsiella pneumoniae (17.65%), Serratia odorifera (15.29%), Escherichia coli (12.94%), Raoultella ornithinolytica, Enterobacter cloacae (11.76%), Serratia marcescens (10.59%), Morganella morganii (7.06%), Proteus mirabilis (5.88%), Acinetobacter baumannii (4.70%) and Pseudomonas aeruginosa (2.35%). All strains were resistant or intermediate to imipenem and/or ertapenem. ESBL, carbapenemase and metallo-beta-lactamases (MBL) phenotypes were detected in 19 (22.35%), 9 (10.59%) and 2 (2.35%) GNB isolates, respectively. PCR results in nine carbapenemase-producing GNB strains chosen showed the presence of one to four carbapenemase genes (blaGES, blaSME, blaNDM-1, blaVIM, blaGIM, blaSPM, blaOXA-48) in four strains; however, seven strains had at least one ESBL gene (blaTEM-1, blaCTXM-15, blaSHV)., Conclusions: In this study, we report the first incidence of blaNDM-1 gene in Enterobacter cloacae isolated from urine sample in Algeria., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Manel Debabza, Raoudha Dziri, Abdelbasset Mechai, Amel Bouguessa, Naouel Klibi, Hadda Imene Ouzari.)