Flies from a tertiary hospital in Rwanda carry multidrug-resistant Gram-negative pathogens including extended-spectrum beta-lactamase-producing E. coli sequence type 131

Prevalence of multidrug-resistant (MDR) gram-negative (GN) bacteria is increasing globally and is complicated by patient movement between acute and long-term care facilities (LTCFs). In Asia, the contribution of LTCFs as a source of MDR GN infections is poorly described. We aimed to define the association between residence in LTCFs and MDR GN bloodstream infections (BSIs). Secondary analysis of data from an observational cohort. Two tertiary referral hospitals in Singapore, including the 1,400-bed Tan Tock Seng Hospital and the 1,600-bed Singapore General Hospital. Adult patients with healthcare-onset (HCO) or hospital-onset (HO) GN BSI. Patients were identified from hospital databases using standard definitions. Risk factors for both MDR GN HCO and HO BSI were analyzed using a multivariable logistic regression model. A total of 675 episodes of GN BSI occurred over a 31-month period. Residence in a LTCF was an independent risk factor for developing MDR GN BSI (odds ratio [OR], 5.1 [95% confidence interval (CI), 2.2-11.9]; P < .01) when antibiotics were not used within the preceding 30 days. This risk persisted beyond the first 48 hours of hospitalization (OR, 3.4 [95% CI, 1.3-9.0]; P = .01). Previous culture growing an MDR organism (OR, 1.8 [95% CI, 1.3-2.7]; P < .01), previous antibiotic use (OR, 1.8 [95% CI, 1.2-2.6]; P < .01), and intensive care unit stay (OR, 2.2 [95% CI, 1.2-3.9]; P = .01), increased the risk of MDR GN BSI. Residence in a LTCF is an independent risk factor for MDR GN BSI. Attempts to contain MDR GN bacteria in large Asian cities, where the proportion of the population that is elderly is projected to increase, should include infection prevention strategies that engage LTCFs.

Antimicrobial resistance has become a significant public health problem globally with multidrug resistant Gram negative (MDR-GN) bacteria being the main representatives. The emergence of these pathogens in neonatal settings threatens the well-being of the vulnerable neonatal population given the dearth of safe and effective therapeutic options. Evidence from studies mainly in adults is now available for several novel antimicrobial compounds, such as new β-lactam/β-lactamase inhibitors (e.g., ceftazidime-avibactam, meropenem-vaborbactam, imipenem/cilastatin-relebactam), although old antibiotics such as colistin, tigecycline, and fosfomycin are also encompassed in the fight against MDR-GN infections that remain challenging. Data in the neonatal population are scarce, with few clinical trials enrolling neonates for the evaluation of the efficacy, safety, and dosing of new antibiotics, while the majority of old antibiotics are used off-label. In this article we review data about some novel and old antibiotics that are active against MDR-GN bacteria causing sepsis and are of interest to be used in the neonatal population.

Low prevalence of colonization with multidrug-resistant gram-negative bacteria in long-term care facilities in Graz, Austria

BackgroundVeno-venous extracorporeal membrane oxygenation (V-V ECMO) is a rapidly expanding life-support technique worldwide. The most common indications are severe hypoxemia and/or hypercapnia, unresponsive to conventional treatments, primarily in cases of acute respiratory distress syndrome. Concerning potential contraindications, there is no mention of microbiological history, especially related to multi-drug resistant (MDR) bacteria isolated before V-V ECMO placement. Our study aims to investigate: (i) the prevalence and incidence of MDR Gram-negative (GN) bacteria in a cohort of V-V ECMOs; (ii) the risk of 1-year mortality, especially in the case of predetected MDR GN bacteria; and (iii) the impact of annual hospital V-V ECMO volume on the probability of acquiring MDR GN bacteria.MethodsAll consecutive adults admitted to the Intensive Care Units of 5 Italian university-affiliated hospitals and requiring V-V ECMO were screened. Exclusion criteria were age < 18 years, pregnancy, veno-arterial or mixed ECMO-configuration, incomplete records, survival < 24 h after V-V ECMO. A standard protocol of microbiological surveillance was applied and MDR profiles were identified using in vitro susceptibility tests. Cox-proportional hazards models were applied for investigating mortality.ResultsTwo hundred and seventy-nine V-V ECMO patients (72% male) were enrolled. The overall MDR GN bacteria percentage was 50%: 21% (n.59) detected before and 29% (n.80) after V-V ECMO placement. The overall 1-year mortality was 42%, with a higher risk observed in predetected patients (aHR 2.14 [1.33–3.47], p value 0.002), while not in ‘V-V ECMO-acquired MDR GN bacteria’ group (aHR 1.51 [0.94–2.42], p value 0.090), as compared to ‘non-MDR GN bacteria’ group (reference). Same findings were found considering only infections. A larger annual hospital V-V ECMO volume was associated with a lower probability of acquiring MDR GN bacteria during V-V ECMO course (aOR 0.91 [0.86–0.97], p value 0.002).Conclusions21% of MDR GN bacteria were detected before; while 29% after V-V ECMO connection. A history of MDR GN bacteria, isolated before V-V ECMO, was an independent risk factor for mortality. The annual hospital V-V ECMO volume affected the probability of acquiring MDR GN bacteria.Trial Registration ClinicalTrial.gov Registration Number NCTNCT06199141, date 12.26.2023.

BackgroundInfections are one of the most common causes of death after lung transplant (LT). However, the benefit of ‘targeted’ prophylaxis in LT recipients pre-colonized by Gram-negative (GN) bacteria is still unclear.MethodsAll consecutive bilateral LT recipients admitted to the Intensive Care Unit of the University Hospital of Padua (February 2016–2023) were retrospectively screened. Only patients with pre-existing GN bacterial isolations were enrolled and analyzed according to the antimicrobial surgical prophylaxis (‘standard’ vs. ‘targeted’ on the preoperative bacterial isolation).ResultsOne hundred eighty-one LT recipients were screened, 46 enrolled. Twenty-two (48%) recipients were exposed to ‘targeted’ prophylaxis, while 24 (52%) to ‘standard’ prophylaxis. Overall prevalence of postoperative multi-drug resistant (MDR) GN bacteria isolation was 65%, with no differences between the two surgical prophylaxis (p = 0.364). Eleven (79%) patients treated with ‘standard’ prophylaxis and twelve (75%) with ‘targeted’ therapy reconfirmed the preoperative GN pathogen (p = 0.999). The prevalence of postoperative infections due to MDR GN bacteria was 50%. Of these recipients, 4 belonged to the ‘standard’ and 11 to the ‘targeted’ prophylaxis (p = 0.027).ConclusionsThe administration of a ‘targeted’ prophylaxis in LT pre-colonized recipients seemed not to prevent the occurrence of postoperative MDR GN infections.

Background Bacterial infection remains the most common cause of morbidity and mortality in pediatric patients with burn wounds. The increase in infection and multidrug-resistant (MDR) pathogens necessitates a periodic review of antimicrobial susceptibility patterns in the burn units. The study aimed to determine the magnitude of multidrug-resistant Gram-negative (MDRGN) bacteria in children with burn wound infections and describe the resistance patterns in the tertiary and regional hospitals in Dar es Salaam, Tanzania. Materials and Methods The study was a hospital-based cross-sectional study design conducted between May 2017 and February 2018. Bacterial isolates from 103 wound swabs of pediatric patients with burn wounds were identified using conventional methods and API 20E. The antimicrobial susceptibility pattern was determined by the Kirby–Bauer disc diffusion method. Data were analyzed using Statistical Package for Social Science (SPSS) version 23.0. Results A total of 136 pathogenic Gram-negative organisms were isolated from burn wound infections in pediatric patients. The most isolated Gram-negative bacterium was Pseudomonas aeruginosa (39.0%), followed by Acinetobacter spp. (28.7%) and Klebsiella spp. (16.2%). MDRGN strains made up 80.1% of all Gram-negative isolates. All (100%) Klebsiella spp. and E. coli were MDR, while 69.2% and 79.2% of Acinetobacter spp. and P. aeruginosa, respectively, displayed MDR strains. We observed high levels of resistance to commonly prescribed antibiotics. Among P. aeruginosa isolates, highest resistance (81.8%) was seen toward meropenem and piperacillin, 79.5% of Acinetobacter spp. showed resistance to aztreonam, while 93–100% of Klebsiella spp and E. coli displayed resistance to amoxyclavulanic acid, ceftriaxone, and ceftazidime. The proportion of extended-spectrum beta-lactamase producers among Enterobacteriaceae was 78.6%. There was a significant higher rate of infection with MDRGN organisms in pediatric patients with a higher percentage of total burn surface area (TBSA) than patients with lower TBSA (p = 0.016). Conclusions P. aeruginosa, Acinetobacter spp., and Klebsiella spp. are the common Gram-negative pathogens causing burn wound infections in hospitalized pediatric patients in our setting. A high proportion of these organisms were multidrug resistant. The findings appeal for regular antimicrobial resistance surveillance in burn wound infection to inform empirical therapy.

Multidrug-Resistant and Extended-Spectrum β-Lactamase Gram-Negative Bacteria in Bilateral Lung Transplant Recipients: Incidence, Risk Factors, and In-Hospital Mortality

Pre-Transplant Colonization By a Multidrug-Resistant Gram Negative Bacteria Has No Impact on Overall Survival and Mortality after Hematopoietic Stem Cell Transplantation: A Single-Center Experience in 362 Patients

Background As gram-negative (GN) resistance continues to rise, it is imperative to understand the best empiric treatment options on a local or regional level. Traditional antibiograms including all isolates may be diluted by sensitive organisms that do not have broad spectrum agents automated for susceptibility testing. The purpose of this review was to develop a health system antibiogram and assess susceptibility rates specific to multidrug-resistant (MDR) GN organisms, including newer broad-spectrum agents that are not routinely reported on traditional antibiograms. Multidrug-Resistant Gram-Negative Antibiogram 2017-2023 Methods Data was collected from acute care facilities within a large community hospital system. MDR GN isolates including extended spectrum β-lactamase-producing (ESBL) Enterobacterales, carbapenem-resistant (CR) Enterobacterales, difficult-to-treat (DTR) Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and Burkholderia cepacia complex from January 2017 to December 2023 were included. Susceptibility testing was completed using VITEK 2 system (bioMérieux), E-test or Kirby-Bauer disk diffusion. Interpretation of susceptibility data was based on CLSI M100 guidance. Results The MDR GN antibiogram is shown in Table 1. The most common isolates encountered were ESBL Escherichia coli (n=8797) and ESBL Klebsiella pneumoniae (n=1779). DTR P. aeruginosa had the lowest susceptibility across all agents; in comparison to CR P. aeruginosa isolates, ceftazidime/avibactam susceptibility was similar however ceftolozane/tazobactam susceptibility was lower. Notably, ceftazidime/avibactam (100%) retained activity for CR K. pneumoniae while CR E. coli had a lower than expected isolate count and susceptibility. S. maltophilia had lower reported susceptibility to trimethoprim/sulfamethoxazole and levofloxacin (84% and 86% respectively) than minocycline (95%) which is performed upon request via manual E-test. Conclusion Most MDR GN pathogens within a large community hospital system had reported activity to newer antimicrobial agents. Overall, our antibiogram aligns with treatment recommendations advised by IDSA 2023 Antimicrobial Resistance guidance. Next steps include additional data review for annual susceptibility trends. Disclosures All Authors: No reported disclosures

Multidrug resistant gram-negative bacteria in Tasmania: An audit based pilot study

Management of Infections Caused by Multidrug-resistant Gram-negative Pathogens: Recent Advances and Future Directions

The epidemiology of bacteremia developing during neutropenia has changed in the past decade, with the re-emergence of Gram-negative (GN) bacteria and the development of multidrug resistance (MDR) among GN bacteria. We conducted a case-control study in order to identify factors associated with bacteremia due to multidrug-resistant Gram-negative (MDRGN) isolates in hematopoietic stem cell transplant recipients. Ten patients with MDRGN bacteremia were compared with 44 patients with GN bacteremia without MDR. Bacteremia due to Burkholderia or Stenotrophomonas sp was excluded from analysis (3 cases), because the possibility of intrinsical resistance. Infection due to MDRGN bacteria occurred in 2.9% of 342 hematopoietic stem cell transplant recipients. Klebsiella pneumoniae was the most frequent MDRGN (4 isolates), followed by Pseudomonas aeruginosa (3 isolates). Among non-MDRGN, P. aeruginosa was the most frequent agent (34%), followed by Escherichia coli (30%). The development of GN bacteremia during the empirical treatment of febrile neutropenia (breakthrough bacteremia) was associated with MDR (P < 0.001, odds ratio = 32, 95% confidence interval = 5_190) by multivariate analysis. Bacteremia due to MDRGN bacteria was associated with a higher death rate by univariate analysis (40 vs 9%; P = 0.03). We were unable to identify risk factors on admission or at the time of the first fever, but the occurrence of breakthrough bacteremia was strongly associated with MDRGN bacteria. An immediate change in the antibiotic regimen in such circumstances may improve the prognosis of these patients.

Bloodstream Infections Due to Multidrug-Resistant Gram-Negative Organisms in Hematopoietic Stem Cell Transplant Recipients: A Multicenter Case-Control Study in a High-Prevalence Area.

Predictors of mortality in patients with infections due to multi-drug resistant Gram negative bacteria: The study, the patient, the bug or the drug?

Inhalation Alone versus Inhalation Plus Intravenous Colistin for Multidrug-Resistant Gram-Negative Bacterial Infection After Lung Transplantation