RESUMO
The AIDA randomized clinical trial found no significant difference in clinical failure or survival between colistin monotherapy and colistin-meropenem combination therapy in carbapenem-resistant Gram-negative infections. The aim of this reverse translational study was to integrate all individual preclinical and clinical pharmacokinetic-pharmacodynamic (PKPD) data from the AIDA trial in a pharmacometric framework to explore whether individualized predictions of bacterial burden were associated with the trial outcomes. The compiled dataset included for each of the 207 patients was (i) information on the infecting Acinetobacter baumannii isolate (minimum inhibitory concentration, checkerboard assay data, and fitness in a murine model), (ii) colistin plasma concentrations and colistin and meropenem dosing history, and (iii) disease scores and demographics. The individual information was integrated into PKPD models, and the predicted change in bacterial count at 24 h for each patient, as well as patient characteristics, was correlated with clinical outcomes using logistic regression. The in vivo fitness was the most important factor for change in bacterial count. A model-predicted growth at 24 h of ≥2-log10 (164/207) correlated positively with clinical failure (adjusted odds ratio, aOR = 2.01). The aOR for one unit increase of other significant predictors were 1.24 for SOFA score, 1.19 for Charlson comorbidity index, and 1.01 for age. This study exemplifies how preclinical and clinical anti-infective PKPD data can be integrated through pharmacodynamic modeling and identify patient- and pathogen-specific factors related to clinical outcomes - an approach that may improve understanding of study outcomes.
Assuntos
Acinetobacter baumannii , Antibacterianos , Meropeném , Testes de Sensibilidade Microbiana , Humanos , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Meropeném/farmacocinética , Meropeném/administração & dosagem , Meropeném/farmacologia , Pessoa de Meia-Idade , Feminino , Masculino , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Colistina/farmacocinética , Colistina/administração & dosagem , Adulto , Idoso , Animais , Resultado do Tratamento , Camundongos , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Pesquisa Translacional Biomédica , Quimioterapia Combinada/métodos , Modelos BiológicosRESUMO
Background: We examined temporal trends in carbapenem-resistant Acinetobacter baumannii (CRAB) infections in a hospital with hyperendemic CRAB and assessed the efficacy of varied infection control strategies in different ward types. Methods: We retrospectively analyzed all CRAB clinical samples from 2006 to 2019 and categorized infections as hospital-onset (HO) or community-onset. We used interrupted time series analysis to assess the impact of interventions on the incidence of all HO-CRAB infections and bloodstream infections (BSIs) at the hospital and ward group levels. Results: Over 14 years, 4009 CRAB infections were identified (89.7% HO), with 813 CRAB BSI (93.2% HO). The incidence per 100 000 patient-days of CRAB infections peaked in 2008 at 79.1, and that of CRAB BSI peaked in 2010 at 16.2. These rates decreased by two-thirds by 2019. In the general intensive care unit (ICU), hand hygiene and environmental cleaning interventions were followed by a significant reduction in the level of HO-CRAB infections, with an additional decrease in the slope after the introduction of active surveillance and 2% chlorhexidine bathing. In the surgical ICU and surgical department, a reduction in slope or level of CRAB infection was observed after moving ventilated patients to single rooms. In medical wards, a multimodal intervention was followed by a reduction in the slope of HO-CRAB infections and BSIs. In wards where CRAB infections were uncommon, the incidence of HO-CRAB infections decreased throughout the study period. Conclusions: Ward-specific variables determine the success of interventions in reducing CRAB infections; therefore, interventions should be tailored to each setting.
RESUMO
The use of mammalian models for in vivo testing of bacterial virulence raises ethical concerns and is expensive and time-consuming. As an alternative, non-mammalian models are sought. Galleria mellonella larvae have been used as a model to study several bacterial pathogens. However, their maintenance is challenging, and commercial supply is low. In this study, we aimed to establish the Zophobas morio larvae as an alternative non-mammalian model for the evaluation of the pathogenicity and antimicrobial susceptibility of Acinetobacter baumannii. We infected Z. morio with Acinetobacter strains and determined the optimal temperature and inoculum. To visualize the bacterial distribution within the larvae, hematoxylin and eosin (H&E) staining was performed. Next, a survival model of infected larvae was established, and virulence was compared between strains. The effect of antimicrobial treatment in relation to antibiotic susceptibility was studied. Our results demonstrate that Z. morio can be used as a model system for in vivo studies of A. baumannii.
RESUMO
Timely detection of carbapenem-resistant Acinetobacter baumannii (CRAB) carriers is essential to direct infection control measures. In this work, we aimed to develop a practical protocol to detect CRAB from screening samples. To choose a selective medium that detects CRAB with high sensitivity and specificity, 111 A. baumannii clinical isolates were inoculated on three types of agar: mSuperCARBA (SC), CHROMagar Acinetobacter (CaA), and modified CHROMagar Acinetobacter (mCaA) containing 4.5 mg/mL meropenem. SC was non-selective, CaA was the most sensitive (100%), but only moderately specific (72%), and mCaA was highly specific (97%) and sensitive (98%). Confirmation of the carbapenem-resistant phenotype using PCR-based detection of blaOXA-23, blaOXA-24, and blaOXA-58 genes was specific but not sensitive, detecting only 58% of CRAB isolates. Identification of A. baumannii using either gyrB or blaOXA-51 PCR was excellent. Next, we used the same methodology in routine screening for CRAB carriage. mCaA had the best yield, with high sensitivity but moderate specificity to differentiate between CRAB and other carbapenem-resistant organisms. Skin sampling using sponges and 6 hour enrichment was highly sensitive (98%), while other body sites had poor sensitivity (27%- 41%). Shorter incubation had slightly lower yield, and longer incubation did not improve the detection. Performing PCR for blaOXA-51 and gyrB on colonies growing on modified mCaA differentiated between CRAB and other species with high accuracy (98% and 99%, respectively). Based on our results, we present a procedure for easy and reliable detection of CRAB carriage using skin sampling, short enrichment, selection on mCaA, and PCR-based identification. IMPORTANCE: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a substantial cause of nosocomial infections, classified among the most significant multidrug-resistant pathogens by the World Health Organization and by the US Centers for Disease Control. Limiting the spread of CRAB is an important goal of infection control, but laboratory methods for identification of CRAB carriers are not standardized. In this work, we compared different selective agar plates, tested the efficiency of A. baumannii identification by PCR for species-specific genes, and used PCR-based detection of common resistance genes to confirm the carbapenem-resistant phenotype. During a prospective study, we also determined the optimal sample enrichment time. Based on our results, we propose a simple and efficient protocol for the detection of CRAB carriage using skin sampling, short enrichment, selection on appropriate agar plates, and PCR-based identification, resulting in a turn-around time of 24 hours.
Assuntos
Acinetobacter baumannii , beta-Lactamases , beta-Lactamases/genética , Estudos Prospectivos , Ágar , Testes de Sensibilidade Microbiana , Carbapenêmicos/farmacologiaRESUMO
BACKGROUND: Little is known about the risk of progression from carbapenemase-producing Enterobacterales (CPE) carriage to CPE bloodstream infection (BSI) outside of high-risk settings. We aimed to determine the incidence of CPE BSI among CPE carriers and to assess whether the incidence differs by carbapenemase, species, and setting. METHODS: We conducted a nationwide population-based retrospective cohort study using national databases. The cohort consisted of all patients in Israel with CPE detected by screening from 1 January 2020 to 10 October 2022. We calculated the cumulative incidence of CPE BSI within 1 year among CPE carriers. We used a competing-risks model with BSI as the outcome and death as the competing risk. RESULTS: The study included 6828 CPE carriers. The cumulative incidence of CPE BSI was 2.4% (95% confidence interval [CI], 2.1-2.8). Compared with Klebsiella pneumoniae carbapenemase (KPC), the subhazard of BSI was lower for New Delhi metallo-ß-lactamase (NDM) (adjusted subhazard ratio [aSHR], 0.72; 95% CI, .49-1.05) and oxacillinase-48-like (OXA-48-like) (aSHR, 0.60; 95% CI, .32-1.12) but these differences did not reach statistical significance. Compared with K. pneumoniae, the subhazard of BSI was lower for carriers of carbapenemase-producing Escherichia coli (aSHR, 0.33; 95% CI, .21-.52). The subhazard of BSI was higher among patients with CPE carriage first detected in intensive care units (aSHR, 2.10; 95% CI, 1.27-3.49) or oncology/hematology wards (aSHR, 3.95; 95% CI, 2.51-6.22) compared with medical wards. CONCLUSIONS: The risk of CPE BSI among CPE carriers is lower than previously reported in studies that focused on high-risk patients and settings. The risk of BSI differs significantly by bacterial species and setting, but not by carbapenemase.
Assuntos
Bacteriemia , Proteínas de Bactérias , Portador Sadio , Infecções por Enterobacteriaceae , beta-Lactamases , Humanos , beta-Lactamases/metabolismo , Estudos Retrospectivos , Masculino , Feminino , Proteínas de Bactérias/metabolismo , Pessoa de Meia-Idade , Israel/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Idoso , Bacteriemia/microbiologia , Bacteriemia/epidemiologia , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Adulto , Incidência , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Enterobacteriaceae/enzimologia , Enterobacteriaceae/isolamento & purificação , Enterobacteriaceae/efeitos dos fármacos , Idoso de 80 Anos ou maisRESUMO
We aimed to determine whether obtaining two blood cultures (BCs) instead of one improved the detection of bloodstream infections (BSIs) in children. For this descriptive study, we used surveillance data collected in 2019-2021 from all Israeli hospitals serving children. The sample included 178,702 culturing episodes. One BC was taken in 90.1% of all episodes and 98.2% of episodes in the emergency department. A true pathogen was detected in 1687/160,964 (1.0%) of single-culture episodes and 1567/17,738 (8.9%) of two-culture episodes (p < 0.001). The yield was significantly different even when considering only the first BC in two-culture episodes: 1.0% vs. 7.5%. Among 1576 two-culture episodes that were positive for a true pathogen, the pathogen was detected only in the second culture in 252 (16.0%). We estimated that if a second culture had been taken in all episodes, an additional 343 BSIs by a true pathogen would have been detected. Among 1086 two-culture episodes with commensal bacteria, the second BC was sterile in 530 (48.8%), suggesting contamination. A commensal was isolated in 3094/4781 (64.7%) positive single-culture episodes, which could represent BSI or contamination. The yield of a single BC bottle was low, reflecting both lower sensitivity of a single bottle and the taking of single bottles in patients with a low probability of BSI.
RESUMO
BACKGROUND: Efficient infection control during carbapenem-resistant Enterobacterales outbreaks demands rapid and simple techniques for outbreak investigations. WGS, the current gold standard for outbreak identification, is expensive, time-consuming and requires a high level of expertise. Fourier-transform infrared (FTIR) spectroscopy (IR Biotyper) is a rapid typing method based on infrared radiation applied to samples, which provides a highly specific absorption spectrum. OBJECTIVES: To investigate an outbreak of OXA-48-producing Escherichia coli in real-time using FTIR and subsequently compare the results with WGS. METHODS: Twenty-one isolates were collected during a nosocomial outbreak, and identification and antibiotic susceptibilities were confirmed by VITEK®2. FTIR was conducted for all isolates, and nine representative isolates were sequenced. RESULTS: FTIR was able to correctly determine the clonal relatedness of the isolates and to identify the outbreak cluster, as confirmed by WGS. By WGS, isolates in the main FTIR cluster belonged to the same MLST type and core-genome MLST type, and they harboured similar plasmids and resistance genes, whereas the singletons external to the FTIR cluster had different genetic content. CONCLUSIONS: FTIR can operate as a rapid, efficient and reliable first-line tool for outbreak investigations during a real-time ongoing E. coli outbreak, which can contribute to limiting the spread of pathogens.
Assuntos
Infecções por Escherichia coli , Escherichia coli , Humanos , Escherichia coli/genética , Tipagem de Sequências Multilocus , Espectroscopia de Infravermelho com Transformada de Fourier , Infecções por Escherichia coli/epidemiologia , Surtos de Doenças , beta-Lactamases/genética , Antibacterianos/farmacologiaRESUMO
IMPORTANCE: Our study's results provide promising evidence for the incorporation of a high-sensitivity carbapenem-resistant Acinetobacter baumannii (CRAB) screening method in healthcare settings. Such an approach could prove beneficial in enhancing infection prevention and control measures, leading to improved patient outcomes and potentially alleviating the burden of CRAB in healthcare systems.
Assuntos
Acinetobacter baumannii , Infecção Hospitalar , Humanos , Carbapenêmicos/farmacologia , Infecção Hospitalar/epidemiologia , Conduta Expectante , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologiaRESUMO
Beta-lactam resistance can lead to increased mortality, higher healthcare expenses, and limited therapeutic options. The primary mechanism of beta-lactam resistance is the production of extended-spectrum beta-lactamases (ESBL) and AmpC beta-lactamases. The spread of beta-lactamase-producing Enterobacterales via the food chain may create a resistance reservoir. The aims of this study were to determine the prevalence of ESBL/AmpC-producing Enterobacterales in vegetables, to examine the association between EBSL/AmpC-producing bacteria and types of vegetables, packaging, and markets, and to investigate the genetic features of ESBL-producing isolates. The antibiotic susceptibilities were determined using VITEK. Phenotypic ESBL/AmpC production was confirmed using disk diffusion. ESBL-producing isolates were subjected to Fourier-transform infrared (FT-IR) spectroscopy and to whole genome sequencing using Oxford Nanopore sequencing technology. Of the 301 vegetable samples, 20 (6.6%) were positive for ESBL producers (16 Klebsiella pneumoniae and 4 Escherichia coli), and 63 (20.9%) were positive for AmpC producers (56 Enterobacter cloacae complex, 4 Enterobacter aerogenes/cancerogenus, and 3 Pantoea spp., Aeromonas hydrophila, and Citrobacter braakii). The blaCTX-M and blaSHV genes were most common among ESBL-producing isolates. The beta-lactamase genes of the ESBL producers were mainly carried on plasmids. Multilocus sequence typing and FT-IR typing revealed high diversity among the ESBL producers. AmpC producers were significantly more common in leafy greens and ESBL producers were significantly less common in climbing vegetables. The presence of ESBL/AmpC-producing Enterobacterales in raw vegetables may contribute to the dissemination of resistance genes in the community.
RESUMO
Vibrio cholerae carbapenemase (VCC-1) is a chromosomal encoded class A carbapenemase thus far reported in environmental Vibrio cholerae isolates. Here, we report the first isolation of a blaVCC-1 -carrying Aeromonas caviae from a clinical sample in Israel. The isolate was resistant to all ß-lactam agents, including carbapenems. The blaVCC-1 was located on a large plasmid. GC content suggests that the origin of the blaVCC-1 gene is neither Aeromonas nor Vibrio spp. but an unknown progenitor.
Assuntos
Aeromonas caviae , Aeromonas , Vibrio cholerae , Aeromonas caviae/genética , Antibacterianos/farmacologia , Vibrio cholerae/genética , Testes de Sensibilidade Microbiana , beta-Lactamases/genética , Plasmídeos/genética , Aeromonas/genéticaRESUMO
Acinetobacter baumannii (Ab) bloodstream infections (BSIs) are a major public health concern and associated with high mortality. We describe the nationwide incidence, antimicrobial resistance, and mortality of Ab-BSI in Israel using laboratory-based BSI surveillance data from January 2018 to December 2019. During the study period, there were 971 Ab-BSI events (508 in 2018 and 463 in 2019), with an average annual incidence of 8.08/100,000 population. The median age of patients was 72 (IQR 62-83), and 56.4% were males. Two-thirds of Ab-BSI events were hospital-onset (HO), with median day of onset 16 (IQR 9-30). HO-BSI incidence was 0.62/10,000 patient-days (rate per 10,000 patient-days: 2.78, 1.17, and 0.2 for intensive care, medical, and surgical wards, respectively). Carbapenem susceptibility was 23.4%; 41.4% and 14.9% in community and HO events, respectively. The 14-day, 30-day, and 1-year mortality were 51.2%, 59.3%, and 81.4%, respectively. Carbapenem-resistant Ab-BSI were associated with a significantly higher 14-day, 30-day, and 1-year mortality (p < 0.001 for all). In the multivariable model, age (aHR 1.02) and carbapenem resistance (aHR 3.21) were independent predictors of 30-day mortality. In conclusion, Ab-BSIs pose a significant burden with high mortality, especially associated with antimicrobial resistance. Attention should be focused on prevention and improving treatment.
RESUMO
BACKGROUND: Pneumonia and bloodstream infections (BSI) due to extensively drug-resistant (XDR) Acinetobacter baumannii, XDR Pseudomonas aeruginosa, and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections. METHODS: The OVERCOME (Colistin Monotherapy versus Combination Therapy) trial was an international, randomized, double-blind, placebo-controlled trial. We randomly assigned participants to receive colistin (5 mg/kg once followed by 1.67 mg/kg every 8 hours) in combination with either meropenem (1000 mg every 8 hours) or matching placebo for the treatment of pneumonia and/or BSI caused by XDR A. baumannii, XDR P. aeruginosa, or CRE. The primary outcome was 28-day mortality, and secondary outcomes included clinical failure and microbiologic cure. RESULTS: Between 2012 and 2020, a total of 464 participants were randomly assigned to treatment, and 423 eligible patients comprised the modified intention-to-treat population. A. baumannii was the predominant trial pathogen (78%) and pneumonia the most common index infection (70%). Most patients were in the intensive care unit at the time of enrollment (69%). There was no difference in mortality (43 vs. 37%; P=0.17), clinical failure (65 vs. 58%; difference, 6.8 percentage points; 95% confidence interval [CI], -3.1 to 16.6), microbiologic cure (65 vs. 60%; difference, 4.8 percentage points; 95% CI, -5.6 to 15.2), or adverse events (acute kidney injury, 52 vs. 49% [P=0.55]; hypersensitivity reaction, 1 vs. 3% [P=0.22]; and neurotoxicity, 5 vs. 2% [P=0.29]) between patients receiving monotherapy and combination therapy, respectively. CONCLUSIONS: Combination therapy with colistin and meropenem was not superior to colistin monotherapy for the treatment of pneumonia or BSI caused by these pathogens. (Funded by the National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases protocol 10-0065; ClinicalTrials.gov number, NCT01597973.).
RESUMO
BACKGROUND: Breast implant infection and biofilm formation are major concerns in reconstructive and esthetic breast surgery, with significant medical and economic consequences. Staphylococcus is the common pathogen, with rapidly increasing rates of methicillin-resistant Staphylococcus aureus (MRSA). There is no consensus on prevention practices. This study compares the effect of several pocket irrigation and antibiotic prophylaxis regimens on implant colonization and biofilm formation in an established rat model of MRSA-infected silicone breast implants. METHODS: Silicone discs were inserted in a sub-pectoral pocket in 57 rats (114 implants). Implant infection was induced by injection of free planktonic MRSA into the surgical pocket. Rats were allocated to study groups treated by different antimicrobial protocols: pocket irrigation with vancomycin, povidone-iodine, or saline. Each group was divided into subgroups treated with or without additional peri-operative systemic vancomycin. Implant colonization or overt infection was assessed at post-operative day 14 both clinically and by cultures. RESULTS: Pocket irrigation with vancomycin prevented contamination in 87% of implants. Irrigation and systemic vancomycin prevented contamination in 100% of implants with no difference between a single preoperative dose and a 48-h regimen. Systemic vancomycin alone or irrigation with povidone-iodine alone resulted in 100% contamination rates. CONCLUSIONS: In this in vivo model, combination of systemic vancomycin with vancomycin pocket irrigation was the most effective regimen, preventing contamination in 100% of implants. Continuation of post-operative antibiotic treatment showed no added advantage.
Assuntos
Anti-Infecciosos , Implantes de Mama , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Ratos , Animais , Povidona-Iodo/farmacologia , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Implantes de Mama/efeitos adversos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Silicones/farmacologia , Silicones/uso terapêutico , Infecções Estafilocócicas/prevenção & controleRESUMO
BackgroundCentral line-associated bloodstream infection (CLABSI) is among the most common preventable infectious complications in patients in intensive care units (ICU). In 2011, the Israel National Center for Infection Control initiated a nationwide CLABSI prevention programme.AimTo evaluate the impact of different components of the programme on CLABSI and non-CLABSI rates in medical-surgical ICUs.MethodsWe included data collected from all 29 medical-surgical ICUs in Israel from November 2011 to December 2019. The study period was divided into three phases: I (baseline, initial CLABSI prevention guidelines introduced, initial feedback on rates provided), II (initial guidelines widely implemented, surveillance undertaken, feedback continued) and III (after implementation of additional prevention measures). Interrupted time series analysis was used to compare CLABSI and non-CLABSI rates during the three phases.ResultsThe pooled mean (SD) incidence of CLABSI per 1,000 central line-days dropped from 7.4 (0.38) in phase I to 2.1 (0.13) in phase III (p < 0.001). The incidence rate ratio (IRR) was 0.63 (95% CI: 0.51-0.79) between phases I and II, and 0.78 (95% CI: 0.59-1.02) between phases II and III. The pooled mean (SD) incidence of non-CLABSI per 1,000 patient-days declined from 5.3 (0.24) in phase I to 3.4 (0.13) in phase III (p < 0.001).ConclusionNational CLABSI prevention guidelines, surveillance and feedback resulted in significant reductions in CLABSI and non-CLABSI rates. In the wake of further interventions, significant reduction was achieved in ICUs reporting improvement in the uptake of additional prevention measures.
Assuntos
Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Infecção Hospitalar , Sepse , Humanos , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Infecções Relacionadas a Cateter/etiologia , Israel/epidemiologia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/métodos , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Unidades de Terapia Intensiva , Controle de Infecções/métodos , Sepse/epidemiologia , Hospitais , Cuidados CríticosRESUMO
BACKGROUND: Hospital-associated infections (HAIs) are an important cause of morbidity and mortality around the world. Many HAIs are caused by drug-resistant bacterial pathogens, but there are major gaps in our understanding of the number of hospital-associated drug-resistant infections (HARIs) worldwide. As such, we estimated trends in prevalence of HARIs caused by high priority pathogens (Escherichia coli, Acinetobacter spp., Klebsiella spp., Staphylococcus aureus, Enterobacter spp., and Pseudomonas spp.) in 195 countries. METHODS AND FINDINGS: Resistance prevalence estimates were extracted from 474-point prevalence surveys (PPS) from 99 countries published between 2010 and 2020 coupled with country-level estimates of hospitalization rates and length of stay. Prevalence estimates were transformed in yearly incidence of HARIs per year by country and income group. We estimate the global number of HARIs per year to be 136 million (95% credible interval (CI) 26 to 246 million) per year, with the highest burden in China (52 million, 95% CI 10 to 95 million), Pakistan (10 million, 95% CI 2 to 18 million), and India (9 million, 95% CI 3 to 15 million). Among income groups, middle-income countries bore the highest burden of HARIs per year (119 million, 95% CI 23 to 215 million). Our analysis was constrained by the limited number of PPS for HARIs, lack of community-associated data on antibiotic-resistant infections, and our population level analysis. CONCLUSIONS: In this study, we observe, in the absence of systematic surveillance systems for HARIs, a baseline overview of their rates. Our yearly estimates highlight the global threat of HARIs and may help define strategies to tackle resistance in hospital settings.
Assuntos
Antibacterianos , Infecção Hospitalar , Humanos , Prevalência , Incidência , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Escherichia coli , HospitaisRESUMO
Colistin heteroresistance (HR) refers to a bacterial population comprised of several subpopulations with different levels of resistance to colistin. In this study, we discuss the classic form of HR, in which a resistant subpopulation exists within a predominantly susceptible population. We investigated the prevalence of colistin HR and its evolution into full resistance among 173 clinical carbapenem-resistant Acinetobacter baumannii isolates and examined the effect of HR on clinical outcomes. To determine HR, we performed population analysis profiling. Our results showed a high prevalence of HR (67.1%). To examine evolution of HR strains into full resistance, the HR strains were grown in colistin-containing broth, transferred onto colistin-containing plates, and colonies on these plates were transferred into colistin-free broth. Many of the HR strains (80.2%) evolved into full resistance, 17.2% reverted to HR, and 2.6% were borderline. We used logistic regression to compare 14-day clinical failure and 14-day mortality between patients infected by HR versus susceptible non-HR carbapenem-resistant A. baumannii. In the subgroup of patients with bacteremia, HR was significantly associated with 14-day mortality. IMPORTANCE To our knowledge, this is the first large-scale study to report on HR in Gram-negative bacteria. We described the prevalence of colistin HR in a large sample of carbapenem-resistant A. baumannii isolates, the evolution of many colistin HR isolates to a resistant phenotype following colistin exposure and withdrawal, and the clinical consequences of colistin HR. We found a high prevalence of HR among clinical carbapenem-resistant A. baumannii isolates; most evolved into a resistant phenotype following colistin exposure and withdrawal. In patients treated with colistin, evolution of HR A. baumannii into full resistance could lead to higher rates of treatment failure and contribute to the reservoir of colistin-resistant pathogens in health care settings.
Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Humanos , Colistina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Prevalência , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , Testes de Sensibilidade Microbiana , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana MúltiplaRESUMO
The environment surrounding 30 of 31 carriers of carbapenem-resistant Acinetobacter baumannii (CRAB) was contaminated by CRAB. The environmental CRAB loads were similar whether carriers were identified only by surveillance cultures (nonclinical carriers) or also had positive clinical cultures. Screening to detect and isolate nonclinical CRAB carriers may be important to prevent CRAB transmission.
Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Humanos , Carbapenêmicos/farmacologia , Infecções por Acinetobacter/epidemiologia , Testes de Sensibilidade Microbiana , Controle de Infecções , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
A positive "string test" indicates the ability of bacterial colonies grown on agar plates to form viscous strings of >5 mm when stretched. This phenotype is strongly associated with hypervirulence in Klebsiella pneumoniae but has never been described in carbapenem-resistant Acinetobacter baumannii (CRAB), an emerging human pathogen of high clinical significance. In this work, we screened 1,000 CRAB isolates, among which we identified and characterized 9 string-positive CRAB (stCRAB) isolates. Phenotypic and genotypic analyses revealed that the isolates were not phylogenetically related and possessed different antibiotic resistance and virulence profiles. Transmission electron microscopy (TEM) showed the presence of capsule in string-positive isolates. String-positive isolates were more motile but did not form more biofilm than non-string-positive isolates. They were less virulent in a murine thigh fitness model and a Galleria mellonella survival assay. In conclusion, here, we describe string-positive A. baumannii isolates and their phenotypic and molecular characteristics. We found that unlike K. pneumoniae, stCRAB isolates were not associated with increased virulence. IMPORTANCE Acinetobacter baumannii has been considered a major health care threat in recent years. Despite many efforts, the pathogenesis and molecular mechanism of A. baumannii virulence remain poorly understood. Moreover, the plasticity of its genome frequently gives rise to new and more virulent isolates. Our current study is of significant importance as it concerns a previously undescribed A. baumannii phenotype. The string-positive phenotype is strongly associated with increased fitness and virulence in other Gram-negative bacteria such as K. pneumoniae. Although no clear correlation with virulence or fitness was found in our 9 stCRAB isolates, this could have been due to the limited statistical power of our research. We suggest that this phenotype should be taken into consideration as due to its genome plasticity, the next change can give rise to string-positive and hypervirulent strains, as is known for K. pneumoniae. Additional future research is needed regarding its possible consequences.
RESUMO
BACKGROUND: We sought to determine incidence of common hospital-acquired bacteria among coronavirus disease 2019 (COVID-19) patients in Israeli general hospitals during the first year of the pandemic. METHODS: We analyzed routinely collected incidence data to determine hospital acquisition of the following sentinel bacteria: Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Pseudomonas aeruginosa, Acinetobacter baumannii, and Clostridioides difficile. We examined 3 acquisition measures: (1) sentinel bacteria, (2) sentinel bacteremia, and (3) antimicrobial-resistant sentinel bacteremia. The study period was March 1, 2020, through January 31, 2021. RESULTS: Analysis of pooled data from the 26 hospitals surveyed revealed that rates were higher for all 3 acquisition measures among COVID-19 patients than they were among patients on general medical wards in 2019, but lower than those among patients in intensive care units in 2019. The incidence rate was highest during the first COVID-19 wave, despite a lower proportion of severe COVID-19 cases among total hospitalized during this wave. Wide variation in incidence was evident between hospitals. CONCLUSIONS: Hospitalized COVID-19 patients experienced nosocomial bacterial infection at rates higher than those of patients on pre-pandemic general medical wards, adding to the complexity of their care. Lower rates of nosocomial infection after the first wave, despite higher proportions of severely ill patients, suggest that healthcare worker practices, rather than patient-related factors, were responsible for most of these infections.
Assuntos
Bacteriemia , Infecções Bacterianas , COVID-19 , Infecção Hospitalar , Humanos , Antibacterianos/farmacologia , Israel/epidemiologia , Farmacorresistência Bacteriana , COVID-19/epidemiologia , Bactérias , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Hospitais Gerais , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Testes de Sensibilidade MicrobianaRESUMO
We used Fourier-transform infrared (FTIR) spectroscopy to analyze 4 carbapenem-resistant Acinetobacter baumannii outbreaks. FTIR distinguished between isolates from different hospitals and uncovered the relatedness between isolates from acute-care hospitals and a post-acute-care hospital. Using higher cutoffs reveals more distant relationships and lower cutoffs support analyses of recent events.