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Antibiogram and Genetic Characterization of Carbapenem-Resistant Gram-Negative Pathogens Incriminated in Healthcare-Associated Infections.

ABSTRACT: Purpose:Carbapenems are considered the most efficient antibiotic used in the treatment of nosocomial infections. Carbapenem-resistant Gram-negative rods are becoming a serious hazard in hospitals threatening public health. The aim of the current study was to investigate the prevalence of carbapenem-resistant Gram-negative pathogens incriminated in healthcare-associated infections, along with antimicrobial resistance profiles, carbapenemase and metallo-?-lactamase production, and their molecular characterization. Methods:A total of 186 clinical specimens were collected from 133 patients at various hospitals in Cairo, Egypt. The obtained specimens were subjected to bacteriological examination, antimicrobial susceptibility testing, detection of carbapenemase production using the modified Hodge test (MHT), the metallo-?-lactamase production using the EDTA combined disc test (CDT), and PCR-based detection of the bla KPC and bla GES resistance genes. The identification of the highly resistant retrieved isolates was then confirmed by 16S rRNA gene sequencing. Results:The most common isolated Gram-negative species was Klebsiella pneumoniae (40.9%), followed by Acinetobacter baumannii (18.8%), Pseudomonas aeruginosa (17.3%), Escherichia coli (15.4%), Enterobacter aerogenes (5.3%), and Proteus mirabilis (2.4%). The prevalence of carbapenem-resistant isolates was 36.1% (n=75). However, 86.5% of the recovered clinical isolates were susceptible to colistin. The MHT revealed that 33.6% (n=70) of the tested strains were positive for carbapenemase production, while the CDT showed that 33.17% (n=69) of the examined strains were metallo-?-lactamase producers. The PCR revealed that 98.6% (74/75) of the tested strains possessed the bla KPC gene; moreover, 97.3% (73/75) of the examined strains harbored the bla GES gene. Conclusion:This study displayed the emergence of carbapenem-resistant Gram-negative pathogens incriminated in healthcare-associated infections. The accurate identification of carbapenem-resistant bacterial pathogens is pivotal for the treatment of patients, in addition to propelling appropriate contamination control measures to restrain the fast spread of such pathogens. Colistin showed a potent in vitro antimicrobial activity against the carbapenem-resistant strains.

SUBMITTER: Makharita RR

PROVIDER: S-EPMC7649219 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Antibiogram and Genetic Characterization of Carbapenem-Resistant Gram-Negative Pathogens Incriminated in Healthcare-Associated Infections.

Makharita Rabab R RR El-Kholy Iman I Hetta Helal F HF Abdelaziz Moahmed H MH Hagagy Fatma I FI Ahmed Amera A AA Algammal Abdelazeem M AM

Infection and drug resistance 20201104

<h4>Purpose</h4>Carbapenems are considered the most efficient antibiotic used in the treatment of nosocomial infections. Carbapenem-resistant Gram-negative rods are becoming a serious hazard in hospitals threatening public health. The aim of the current study was to investigate the prevalence of carbapenem-resistant Gram-negative pathogens incriminated in healthcare-associated infections, along with antimicrobial resistance profiles, carbapenemase and metallo-β-lactamase production, and their mo ...[more]

PMID: 33177849

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Project description:BACKGROUND:Rates of colonization and infection with carbapenem-resistant Gram-negative pathogens are on the rise, particularly in southeastern European countries, and this is increasingly true in Germany as well. The organisms in question include enterobacteriaceae such as Klebsiella pneumoniae and Escherichia coli and non-fermenting bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. As the carbapenems have been the gold standard to date for the systemic treatment of serious infections with Gram-negative bacteria, carbapenem resistance presents new and difficult challenges in therapeutic decision-making, particularly because of the high frequency of coresistance. METHODS:This review is based on pertinent publications retrieved by a selective search in PubMed and on other applicable literature. RESULTS:Multiresistant Gram-negative (MRGN) pathogens are classified in Germany according to their resistance to four different classes of antibiotics; fluoroquinolones, piperacillin, third-generation cephalosporins, and carbapenems. Quadruple MRGN pathogens are resistant to all four groups, triple MRGN pathogens to three of them. There are a number of therapeutic alternatives to carbapenems that can be applied with the aid of sensitive microbiological and/or molecular genetic testing. The following antibiotics are often the only ones that can be used to treat quadruple MRGN pathogens: colistin, aminoglycosides, tigecycline, fosfomycin, ceftazidime/avibactam, and ceftolozan/tazobactam. Carbapenems, too, may still be an option in certain situations. There is also evidence that combinations of antibiotics against which the pathogen is resistant individually can some- times be a valid treatment option; these include combinations of colistin with one or two carbapenems. CONCLUSION:The treatment of severe infection with carbapenem-resistant pathogens should be individualized and carried out in an interdisciplinary framework, in consideration of antibiotic pharmacokinetics and pharmacodynamics in each case. The treat- ment options are based on evidence from in vitro studies, retrospective studies, and case series, which must be interpreted with caution. Randomized clinical trials are needed to test each of the various combined approaches.

Project description:Carbapenem-resistant Gram-negative bacteria (CRGNB)-related health care-associated ventriculitis and meningitis (HCAVM) is dangerous. We aimed to report the antimicrobial resistance of the pathogens, treatment, and outcome. All cases with CRGNB-related HCAVM in2012-2020 were recruited. Antimicrobial agents were classified as active, untested, or inactive using antimicrobial susceptibility tests. The treatment stage was classified as empirical or targeted according to the report of pathogens. The treatment effect was classified as ineffective or effective according to HCAVM-related parameters. Overall, 92 cases were recruited. For most antimicrobial agents, the resistance rate was higher than 70.0%. The polymyxin resistance rate was the lowest at 11.6%. The chloramphenicol, trimethoprim-sulfamethoxazole, amikacin, levofloxacin, and tetracycline resistance rates were relatively low, ranging from 21.1% to 64.1%. The meropenem resistance rate was 81.9%. There was no significant trend for any antimicrobial agent tested. Meropenem was the most common antimicrobial agent used in empirical treatment; trimethoprim-sulfamethoxazole and polymyxin were the most used active antimicrobial agents, and meropenem/sulbactam and polymyxin were the most used untested antimicrobial agents in targeted treatment. In total, 42 (45.7%) cases received ineffective treatments. The ineffective treatment rate of cases that received active antimicrobial agents was lower than that of cases that received untested antimicrobial agents and cases that received inactive antimicrobial agents (29.3% [12/41] versus 46.2% [18/39] versus 100.0% [12/12], P < 0.001). Antimicrobial resistance was prevalent but without increasing trends. Active antimicrobial agents are necessary. Additionally, untested antimicrobial agents, including meropenem/sulbactam and polymyxin, might be optional. Inactive antimicrobial agents must be replaced. IMPORTANCE Carbapenem-resistant Gram-negative bacteria-related health care-associated ventriculitis and meningitis is a clinical threat because of the poor outcome and challenges in treatment. We reached several conclusions: (i) the antimicrobial resistance of pathogens is severe, and some antimicrobial agents represented by polymyxin are optional according to the antimicrobial susceptibility tests; (ii) in the background that the portion of carbapenems resistance in Gram-negative bacteria is increasing, there is no increasing trend for the antimicrobial resistance of carbapenem-resistant Gram-negative bacteria in the 9-year study; (iii) meropenem is the main antimicrobial agent in treatment, and trimethoprim-sulfamethoxazole, tigecycline, polymyxin, and meropenem/sulbactam are commonly used in the targeted treatment; (iv) the treatment effect was poor and affected by the treatment: timely active antimicrobial agents should be given. And untested antimicrobial agents represented by polymyxin and meropenem/sulbactam might be optional. Inactive antimicrobial agents must be replaced.

Project description:IntroductionInfections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) are a significant cause of mortality and represent a serious challenge to health systems. The early identification of mortality predictors could guide appropriate treatment and follow-up. We aimed to identify the factors associated with 90-day all-cause mortality in patients with CR-GNB infections.MethodsWe conducted a cohort study from 1 January 2019 to 30 April 2022. The primary outcome was death from any cause during the first 90 days after the date of the first CR-GNB-positive culture. Secondary outcomes included infection relapse, invasive mechanical ventilation during follow-up, need for additional source control, acute kidney injury, Clostridioides difficile infection, and all-cause hospital admission after initial discharge. Bivariate and multivariate Cox-proportional hazards models were constructed to identify the factors independently associated with 90-day all-cause mortality.ResultsA total of 225 patients with CR-GNB infections were included. Death occurred in 76 (34%) cases. The most-reported comorbidities were immunosuppression (43%), arterial hypertension (35%), and COVID-19 (25%). The median length of stay in survivors was 18 days (IQR 10-34). Mechanical ventilation and ICU admission after diagnosis occurred in 8% and 11% of cases, respectively. Both infection relapse and rehospitalisation occurred in 18% of cases. C. difficile infection was diagnosed in 4% of cases. Acute kidney injury was documented in 22% of patients. Mechanical ventilation after diagnosis, ICU admission after diagnosis, and acute kidney injury in the first ten days of appropriate treatment were more frequently reported among non-survivors. In the multivariate analysis, age (HR 1.19 (95%CI 1.00-1.83)), immunosuppression (HR 1.84 (95%CI 1.06-3.18)), and septic shock at diagnosis (HR 2.40 (95% 1.41-4.08)) had an independent association with death during the first 90 days after the CR-GNB infection diagnosis. Receiving antibiogram-guided appropriate treatment was independently associated with a lower risk of death (HR 0.25 (95%CI 0.14-0.46)).ConclusionsThe presence of advanced age, immunosuppression, septic shock at diagnosis, and inappropriate treatment are associated with higher 90-day all-cause mortality in hospitalised patients with infections due to CR-GNB. Recognition of the risk factors for adverse outcomes could further assist in patient care and the design of interventional studies that address the severe and widespread problem that is carbapenem resistance.

Dataset Information

Antibiogram and Genetic Characterization of Carbapenem-Resistant Gram-Negative Pathogens Incriminated in Healthcare-Associated Infections.

Publications

Antibiogram and Genetic Characterization of Carbapenem-Resistant Gram-Negative Pathogens Incriminated in Healthcare-Associated Infections.

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