Resistant Gram-negative Bacilli Research Articles

ESBL-producing Enterobacteriaceae, an Unnoticed Pandemic with Challenges in Clinical Practice, a mini-review.

Antimicrobial resistance in gram-negative bacilli is an ecological problem with a major impact on public health. Extended-spectrum β-lactamases (ESBLs) are enzymes that inactivate broad-spectrum antibiotics, penicillins, third and fourth generation cephalosporins. There are many factors associated with the global spread of ESBLs, such as the use of over-the-counter antibiotics, the food industry, travel abroad, and the lack of implementation of control strategies in hospitals and at the community level. Fecal carriers of ESBLs are increasingly commonly encountered in routine hospital settings as many hospitals have implemented rectal screening for ESBLs, however, the utility of this clinical practice and the routine isolation of patients carrying these bacteria has controversial benefits. There are challenges in selecting suitable patients for empirical therapy with carbapenems for the treatment of presumed severe ESBLs infections. Inappropriate empirical therapy is associated with high mortality in bloodstream infections. Carbapenems are the standard of care for severe invasive ESBL-E infections outside the urinary tract, however, overuse of carbapenems may lead to the emergence of carbapenem-resistant Enterobacterales. This mini review is intended to contribute to understanding about ESBLs as a global ecological problem, causing a considerable impact on health care services and posing enormous challenges in everyday antimicrobial therapy.

ESBL-producing Enterobacteriaceae, an Unnoticed Pandemic with Challenges in Clinical Practice, a mini-review.

Antimicrobial resistance in gram-negative bacilli is an ecological problem with a major impact on public health. Extended-spectrum β-lactamases (ESBLs) are enzymes that inactivate broad-spectrum antibiotics, penicillins, third and fourth generation cephalosporins. There are many factors associated with the global spread of ESBLs, such as the use of over-the-counter antibiotics, the food industry, travel abroad, and the lack of implementation of control strategies in hospitals and at the community level. Fecal carriers of ESBLs are increasingly commonly encountered in routine hospital settings as many hospitals have implemented rectal screening for ESBLs, however, the utility of this clinical practice and the routine isolation of patients carrying these bacteria has controversial benefits. There are challenges in selecting suitable patients for empirical therapy with carbapenems for the treatment of presumed severe ESBLs infections. Inappropriate empirical therapy is associated with high mortality in bloodstream infections. Carbapenems are the standard of care for severe invasive ESBL-E infections outside the urinary tract, however, overuse of carbapenems may lead to the emergence of carbapenem-resistant Enterobacterales. This mini review is intended to contribute to understanding about ESBLs as a global ecological problem, causing a considerable impact on health care services and posing enormous challenges in everyday antimicrobial therapy.

The tigecycline resistance mechanisms in Gram-negative bacilli.

Tigecycline, hailed as a pivotal agent in combating multidrug-resistant bacterial infections, confronts obstacles posed by the emergence of resistance mechanisms in Gram-negative bacilli. This study explores the complex mechanisms of tigecycline resistance in Gram-negative bacilli, with a particular focus on the role of efflux pumps and drug modification in resistance. By summarizing these mechanisms, our objective is to provide a comprehensive understanding of tigecycline resistance in Gram-negative bacilli, thereby illuminating the evolving landscape of antimicrobial resistance. This review contributes to the elucidation of current existing tigecycline resistance mechanisms and provides insights into the development of effective strategies to manage the control of antimicrobial resistance in the clinical setting, as well as potential new targets for the treatment of tigecycline-resistant bacterial infections.

Performance of Risk Models for Antimicrobial Resistance in Adult Patients With Sepsis

The results of prediction models that stratify patients with sepsis and risk of resistant gram-negative bacilli (GNB) infections inform treatment guidelines. However, these models do not extrapolate well across hospitals. To assess whether patient case mix and local prevalence rates of resistance contributed to the variable performance of a general risk stratification GNB sepsis model for community-onset and hospital-onset sepsis across hospitals. This was a retrospective cohort study conducted from January 2016 and October 2021. Adult patients with sepsis at 10 acute-care hospitals in rural and urban areas across Missouri and Illinois were included. Inclusion criteria were blood cultures indicating sepsis, having received 4 days of antibiotic treatment, and having organ dysfunction (vasopressor use, mechanical ventilation, increased creatinine or bilirubin levels, and thrombocytopenia). Analyses were completed in April 2024. The model included demographic characteristics, comorbidities, vital signs, laboratory values, procedures, and medications administered. Culture results were stratified for ceftriaxone-susceptible GNB (SS), ceftriaxone-resistant but cefepime-susceptible GNB (RS), and ceftriaxone- and cefepime-resistant GNB (RR). Negative cultures and other pathogens were labeled SS. Deep learning models were developed separately for community-onset (patient presented with sepsis) and hospital-onset (sepsis developed ≥48 hours after admission) sepsis. The models were tested across hospitals and patient subgroups. Models were assessed using area under the receiver operating characteristic curve (AUROC) and area under precision recall curve (AUPRC). A total of 39 893 patients with 85 238 sepsis episodes (43 207 [50.7%] community onset; 42 031 [48.3%] hospital onset) were included. Median (IQR) age was 65 (54-74) years, 21 241 patients (53.2%) were male, and 18 830 (47.2%) had a previous episode of sepsis. RS contributed to 3.9% (1667 episodes) and 5.7% (2389 episodes) of community-onset and hospital-onset sepsis episodes, respectively, and RR contributed to 1.8% (796 episodes) and 3.9% (1626 episodes), respectively. Previous infections and exposure to antibiotics were associated with the risk of resistant GNB. For example, in community-onset sepsis, 375 RR episodes (47.1%), 420 RS episodes (25.2%) and 3483 of 40 744 (8.5%) SS episodes were among patients with resistance to antimicrobial drugs (P < .001). The AUROC and AUPRC results varied across hospitals and patient subgroups for both community-onset and hospital-onset sepsis. AUPRC values correlated with the prevalence rates of resistant GNB (R = 0.79; P = .001). In this cohort study of 39 893 patients with sepsis, variable model performance was associated with prevalence rates of antimicrobial resistance rather than patient case mix. This variability suggests caution is needed when using generalized models for predicting resistant GNB etiologies in sepsis.

Effect of Ceftaroline, Ceftazidime/Avibactam, Ceftolozane/Tazobactam, and Meropenem/Vaborbactam on Establishment of Colonization by Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice.

The potential for promotion of intestinal colonization with healthcare-associated pathogens by new antibiotics used to treat infections due to multidrug-resistant Gram-negative bacilli is unclear. Mice treated for 3 days with daily subcutaneous phosphate-buffered saline (control), ceftazidime/avibactam, ceftolozane/tazobactam, ceftaroline, and meropenem/vaborbactam were challenged with 10,000 colony-forming units (CFU) of vancomycin-resistant Enterococcus (VRE) resistant to each of the antibioics or carbapenemase-producing Klebsiella pneumoniae 1 day after the final treatment dose. The concentrations of VRE or K. pneumoniae in stool were measured on days 1, 3, 6, and 15 after challenge. Control mice had transient low levels of VRE or K. pneumoniae (<3 log10 CFU/g) detected in stool with negative cultures on days 6 and 15 after challenge. In comparison to control mice, each of the antibiotics promoted establishment of high-density colonization with VRE (mean concentration, >8 log10 CFU/g of stool on day 1 after challenge) that persisted at >4 log10 CFU/g of stool through day 15 (P<0.01). In comparison to control mice, meropenem/vaborbactam and ceftaroline promoted high-density colonization with K. pneumoniae (peak concentration, >8 log10 CFU/g of stool) (P<0.01), ceftolozane/tazobactam promoted colonization to a lesser degree (peak concentration, >5 log10 CFU/g of stool), and ceftazidime/avibactam did not promote colonization (P>0.05). Our results suggest that several beta-lactam antibiotics recently developed for treatment of infections with resistant Gram-negative bacilli have the potential to promote colonization by healthcare-associated pathogens. Additional studies are needed to examine the impact of these agents in patients.

Tigecycline Resistant Pattern among Carbapenem Resistant Gram-negative Bacilli: Prospective Cross-sectional Study

Introduction: Tigecycline is a unique tetracycline class of semi-synthetic, last-line broad spectrum antibiotic against multi-drug-resistant bacteria. However, recently, resistance to this antibiotic is on the rise. Aims: This study was conducted to determine the prevalence of tigecycline resistance amongst carbapenem-resistant Gram-negative bacilli (GNB) isolated from clinical samples (pus and sputum) as well as to evaluate their antimicrobial susceptibility pattern. Study design: Prospective cross sectional Place and Duration of Study: Department of Microbiology at Sanjay Gandhi Post Graduate Institute of Medical Sciences Lucknow, between January 2023 and December 2023. Methodology: Identification of GNB grown on culture was done by conventional biochemical tests and later validated by MALDI-TOF MS. The antimicrobial sensitivity testing of isolates was done using the E-test, and disk diffusion method. Minimum inhibitory concentration determination was done by Broth micro-dilution (BMD) method. Results: Amongst 8326 pus and respiratory samples, GNBs were recovered from 63.15% (5258/8326). Of 5258 GNB isolates, 50.74% (2668) were carbapenem-resistant, while 7.85% (413) demonstrated resistance to both tigecycline and carbapenem. Common isolates in this group were Klebsiella pneumoniae (37.04%), Acinetobacter spp. (25.18%), Enterobacter spp. (14.28%) and Escherichia coli (12.59%). BMD results demonstrated highest activity of tigecycline against carbapenem-resistant E. coli, followed by Citrobacter and Enterobacter. It works against resistant strains of Acinetobacter baumannii and K. pneumoniae as well, but in higher concentrations. Conclusion: High tigecycline resistance (one of the last-resort drugs) among carbapenem resistant GNB isolates is a matter of clinical concern, leaving physicians with limited options for treatment of such infections. Proper adherence to the policies of antimicrobial stewardship programs can reduce the emergence of resistance.

Characterisation of carbapenemase-producing Gram-negative bacilli among clinical isolates in a tertiary care centre in Kerala, South India

Background: Infections caused by carbapenem-resistant Gram-negative bacteria are a cause for concern due to the limited choice of antibiotics available for their treatment. Aims, Settings and Design: This study screened multidrug-resistant (MDR) Gram-negative bacilli isolated from clinical samples over a period of one year, for carbapenem resistance and characterised them using phenotypic methods such as combined disc diffusion test (CDDT), modified Hodge test (MHT), E-test for metallo-beta-lactamase (MBL) and molecular method, PCR. Materials and Methods: Two hundred and ten MDR Gram-negative bacilli were screened for carbapenem resistance using Imipenem and Meropenem disc diffusion. These were further checked for carbapenemase production by CDDT, MHT and E-test for MBL. Those positive by E-test were subjected to PCR. Uniplex PCR for New Delhi metallo-beta-lactamase-1 was used for Escherichia coli and Klebsiella pneumoniae , and multiplex PCR for Imipenemase and Verona imipenemase was used for Pseudomonas aeruginosa and Acinetobacter baumannii isolates. Results: Twenty-three (11%) isolates were found to be carbapenem-resistant and included E. coli (six) K. pneumoniae (three), P. aeruginosa (five) and A. baumannii (nine). Seventeen (74%) isolates were positive by phenotypic methods and were subjected to PCR. Out of eight Enterobacteriaceae isolates subjected to PCR, all were positive for bla NDM gene. All were negative for bla KPC gene. All five A. baumannii isolates subjected to PCR were found to contain bla VIM gene. Two out of four P. aeruginosa isolates were positive for bla IMP , one was positive for bla VIM gene. One P. aeruginosa isolate was positive for both bla IMP and bla VIM gene. Conclusions: In view of the increasing resistance of Gram-negative bacilli to carbapenems, rational use of antibiotics needs to be emphasised.

Analysis of antibiotic resistance in Gram-negative bacilli in wild and exotic healthy birds in Brazil: A warning sign

Bacterial antibiotic resistance is a public health problem affecting humans and animals. This study focuses on identifying Gram-negative bacilli (GNB) (MALDI-TOF MS and Klebsiella MALDI TypeR) resistant to antimicrobials in freshly emitted feces of healthy captive and rescued wild birds from a zoo in Brazil. Birds from the zoo and rescued from sixteen different orders were investigated. Resistant bacteria from feces were selected (MacConkey agar with 2 μg/mL cefotaxime). Genomic similarity and plasmid were investigated by Pulsed-Field Gel Electrophoresis of XbaI fragments (XbaI-PFGE) and S1-PFGE. Polymerase Chain Reaction (PCR) was performed to search for beta-lactamase genes. From 80 birds included, 26 from the zoo (50 %) and 18 rescued wild birds (64 %) presented cefotaxime-resistant GNB. E. coli and Klebsiella spp were the most prevalent species. Among 65 isolates from the zoo and rescued wild birds, 75 % were considered multidrug-resistant (MDR). The majority of the isolates were extended-spectrum beta-lactamases (ESBL) producing and resistant to enrofloxacin. blaCTX-M-GROUP-1, blaTEM, and blaSHV were the most detected genes, and blaKPC was detected in K. pneumoniae complex. According to genomic similarity results, some identical profiles were found in birds with no known contact among the zoo or rescued birds. Several isolates carried one to three plasmids (15–350 kb). The presence of multidrug-resistant (MDR) isolates from healthy captive and wild birds brings novel data on the dissemination of these elements to the environment.

Assessment of in vitro antimicrobial activity of ceftazidime-avibactam and phenotypic synergy testing with aztreonam against carbapenem resistant Gram-negative bacilli in a tertiary care hospital

Objectives: Ceftazidime avibactam (CZA) is a drug used against carbapenemase producing Gram-negative bacterial infections. Avibactam (AVI) is a non-beta-lactam-beta-lactamase inhibitor which has no action against metallo-β-lactamase (MBL) enzymes. This inadequacy is counteracted by combining CZA with aztreonam (ATM). The present study aims to denote the in vitro susceptibility pattern of the CZA and CZA-ATM combination in our area. Materials and Methods: In this study conducted prospectively from January to June 2023, the samples growing Enterobacterales and Pseudomonas aeruginosa were proceeded for carbapenemase detection by phenotypic testing for EDTA carbapenem inactivation method and modified carbapenem inactivation method. The minimum inhibitory concentration MIC of CZA was determined by E-strip and interpreted as per clinical and laboratory standard institute (CLSI) guidelines, while synergy testing of CZA and ATM was performed using ATM discs. Statistical Analysis: All data were entered in Microsoft Excel and analyzed for basic statistics. Results: The study included 150 carbapenem resistant organisms (131 Enterobactarales and 19 P. aeruginosa). Among these Enterobacterale strains, 72 (54.9%) were MBL producers. CZA resistance was detected in 69.3% of Klebsiella spp., 61.53% of Escherichia coli, and 50% of Serratia spp. Among Klebsiella spp. and E. coli, 88.9% and 65.2% of MBL isolates showed in vitro synergy to CZA-ATM. Conclusions: The study highlights a good in vitro sensitivity pattern of the CZA and ATM combination. However, we also highlight a growing percentage of non-synergistic interactions that need further genetic evaluation.

Synergistic Effect of Ceftazidime-Avibactam with Aztreonam on Carbapenemase-Positive Klebsiella pneumoniae MBL+, NDM.

The difficulties in attaining effective antibiotic therapy arising from the multidrug resistance of Gram-negative bacilli compel the exploration of new possibilities for synergistic interactions among existing antibiotics. An analysis was conducted to assess the efficacy of two antibiotic therapy regimens in the treatment of infections caused by Klebsiella pneumoniae strains producing carbapenemases (MBL). Two patient groups were considered: Group A - individuals in whom the treatment of infection involved the application of ceftazidime-avibactam in combination with aztreonam. Group B comprised patients subjected to an alternative antibiotic therapy regimen. In the group subjected to the treatment regimen involving ceftazidime-avibactam and aztreonam, as compared to alternative antibiotic combinations, a statistically lower mortality rate during the course of treatment and a faster clinical response to the administered therapy were evident. The results obtained may be applicable to routine in vitro assays performed and serve as valuable guidance for the potential utilization of the positive effect of antibiotic therapy through the synergy between ceftazidime-avibactam and aztreonam. The selection of antibiotics employed in the therapy of invasive infections caused by K. pneumoniae influences the ultimate treatment outcome.

The effect of the COVID-19 pandemic on the incidence and resistance of Gram-negative bacilli and antimicrobial consumption in the intensive care units of a referral hospital in Buenos Aires

There was a reported increase in the antimicrobial consumption in hospitals during the COVID-19 pandemic, accompanied by an increase in infections due to multidrug-resistant (MDR) bacteria. This retrospective time series study from intensive care units in Buenos Aires examined changes in antibiotic consumption (defined daily doses/1000 patients/day), the incidence of Gram-negative bacilli (GNB) and the mechanism of resistance. Antibiotics were categorised into group 1 (agents against MDR GNB) and group 2 (agents against non-MDR infections). Bacteriological samples included respiratory samples and blood cultures. Periods were divided into pre-pandemic (July 2019 to March 2020) and pandemic (April 2020 to March 2022). Correlation coefficients (r) were analysed and the Mann-Whitney test was performed to compare both periods. During the study period, GNB incidence, group 1 antibiotic consumption and resistance mechanisms increased, whereas antibiotics decreased in group 2. A significant positive correlation was seen between the consumption of antibiotics in group 1 and the incidence of GNB (r = 0.63; P < 0.001) and resistance (r = 0.52; P = 0.002). Significant differences were found between pre-pandemic and pandemic periods regarding the medians of group 1 consumption (520 [408-570] vs. 753 [495-851] DDD/1000 patients/day; P = 0.029), incidence of GNB (12 [10-13] vs. 43 [25-52.5] cases/month; P < 0.001) and resistance mechanisms (5 [4-8] vs. 17 [10-25] cases/month; P < 0.001), extended-spectrum beta lactamases (2 [1-2] vs. 6 [3-8] cases/month; P < 0.001) and metallo-beta-lactamases (0 [0-0] vs. 6 [1.75-8.5] cases/month; P < 0.001). During the COVID-19 pandemic, the rise in GNB incidence and the amount of resistance mechanisms significantly correlated with the increase in consumption of agents against MDR strains.

A study on clinico-demographic and microbiological profile of surgical site infection (SSI) in a tertiary care hospital, Kolkata: An alarming trend

The Centres for Disease Control and Prevention (CDC) estimates surgical site infections SSI is major contributor of healthcare associated infections (HAI). Multidrug resistant (MDR) Gram-negative bacilli are emerging pathogens. This study aimed to determine the magnitude of SSI and identify predominant pathogens with their antimicrobial susceptibility patterns. It is a hospital-based descriptive cross-sectional study including 2070 suspected SSI specimens from 25809 surgeries between 1July 2021 to 30 June 2023. Organisms’ identification and AST was done by both conventional and automated methods. Data was collected and analysed on MS-Excel sheet with various charts and tables. In our study SSI rate was 6.3%, much higher than previous study (2.83%) from this institution. SSI rate was highest in plastic surgery (8.2%). Major pathogens of SSI were Gram-negative bacilli e.g., (26.34%), (25.59%) and (74.69%) was predominant among Gram-positive cocci. Gram-negative bacilli including enterobacterales and non-fermenter and showed resistance to major classes of broad- spectrum antibiotics. Methicillin resistance (MRSA) was 43.9%, which indicates need to improve infection control practices. Our study showed significant higher proportion of SSI as compared to previous studies from the same institute with alarming number of isolated MDR Gram-negative bacilli. So, this study focusses the need of robust infection control practices and strict implementation of antimicrobial stewardship to overcome challenges of antimicrobial resistance.

Impact of Gram-Negative Bacilli Resistance Rates on Risk of Death in Septic Shock and Pneumonia.

Sepsis is a major cause of morbidity and mortality worldwide. When selecting empiric antibiotics for sepsis, clinicians are encouraged to use local resistance rates, but their impact on individual outcomes is unknown. Improved methods to predict outcomes are needed to optimize treatment selection and improve antibiotic stewardship. We expanded on a previously developed theoretical model to estimate the excess risk of death in gram-negative bacilli (GNB) sepsis due to discordant antibiotics using 3 factors: the prevalence of GNB in sepsis, the rate of antibiotic resistance in GNB, and the mortality difference between discordant and concordant antibiotic treatments. We focused on ceftriaxone, cefepime, and meropenem as the anti-GNB treatment backbone in sepsis, pneumonia, and urinary tract infections. We analyzed both publicly available data and data from a large urban hospital. Publicly available data were weighted toward culture-positive cases. Excess risk of death with discordant antibiotics was highest in septic shock and pneumonia. In septic shock, excess risk of death was 4.53% (95% confidence interval [CI], 4.04%-5.01%), 0.6% (95% CI, .55%-.66%), and 0.19% (95% CI, .16%-.21%) when considering resistance to ceftriaxone, cefepime, and meropenem, respectively. Results were similar in pneumonia. Local data, which included culture-negative cases, showed an excess risk of death in septic shock of 0.75% (95% CI, .57%-.93%) for treatment with discordant antibiotics in ceftriaxone-resistant infections and 0.18% (95% CI, .16%-.21%) for cefepime-resistant infections. Estimating the excess risk of death for specific sepsis phenotypes in the context of local resistance rates, rather than relying on population resistance data, may be more informative in deciding empiric antibiotics in GNB infections.

The Clinical Efficacy of Adding Ceftazidime/Avibactam to Standard Therapy in Treating Infections Caused by Carbapenem-Resistant Klebsiella pneumonia with blaOXA-48-like Genes.

Ceftazidime/avibactam (CAZ-AVI) is FDA-approved for managing infections caused by resistant gram-negative bacilli, particularly infections via carbapenem-resistant Enterobacterales pathogens. The clinical data are still limited, particularly those in Saudi Arabia. The present study is a retrospective cohort study that was carried out at the Armed Forces Hospital in the southern region of Saudi Arabia to compare the clinical and microbiological outcomes for CAZ-AVI-treated patients as monotherapy and as an add-on to standard therapy for carbapenem-resistant Klebsiella pneumonia (CRKP) OXA-48 infections to those treated with standard drugs. The study included CRKP OXA-48-like infected patients who were administered antibiotics for more than seven days from 1 August 2018 to May 2023. Patients' baseline characteristics and demography were extracted from the clinical records, and their clinical/microbiology efficiencies were assessed as per the corresponding definitions. Univariate and multivariate logistic regressions were conducted to identify the potential independent variable for CAZ-AVI efficiency. A total of 114 patient files were included for the evaluation. Among these patients, 64 used CAZ-AVI combined with standard therapy and were included in the intervention group, and 50 of them used standard therapy and were included in the comparative group. Following analysis, CAZ-AVI's clinical success was 42.2% (p = 0.028), while the intervention versus comparative groups showed decreased 30-day all-cause mortality (50.0% versus 70.0%; p = 0.036) and infection recurrence (7.8% versus 24.0%; p = 0.019), as well as substantially increased rates of microbial eradication (68.8% versus 42.0%; p = 0.007). CAZ-AVI add-on therapy rather than monotherapy showed statistically significant favored clinical and microbial outcomes over the standard therapy. Furthermore, sex (female %), ICU admission, and fever were negatively associated with patients' 30-day all-cause mortality, serving as independent negative factors. Only fever, CRP bio levels, inotropes, and ICU admissions were significant predictors influencing the CAZ-AVI's clinical efficiency. The duration of CAZ-AVI therapy positively influenced CAZ-AVI's microbial eradication, while both WBC counts and fever experiences were negative predictors. This study shows the effective usage of CAZ-AVI against CRKP OXA-48-like infections. The influencing independent variables depicted here should recommend that clinicians individualize the CAZ-AVI dose based on co-existing risk factors to achieve optimal survival and efficacy. Prospective multicenter and randomized control studies are recommended, with individualized CAZ-AVI precision administration implemented based on patients' characteristics.

Prevalence of Extended-spectrum Beta-lactamase (ESBL), Metallo Beta-lactamase (MBL) and Carbapenemase Producing Acinetobacter Species Isolated from Various Clinical Samples in Tertiary Care Hospital

Acinetobacter is an important nosocomial pathogen causing health care associated infections. It is highly antibiotic resistant gram-negative bacilli. The study was done to determine the prevalence of Acinetobacter species isolated from various clinical samples with their antibiotic susceptibility pattern. To determine the antimicrobial susceptibility pattern of the isolated Acinetobacter species and also the multidrug resistant mechanisms by phenotypic characterization. The retrospective study was carried out in patients diagnosed with Acinetobacter infection in the Microbiology Department, Krishna Institute of Medical Sciences, Krishna Vishwa Vidyapeeth, Deemed To Be University, Karad, a tertiary care hospital, including the clinical departments, during the period of two years from November 2020 till November 2022. Organism identification, biochemical test, antibiotic resistance pattern and phenotypic tests such as ESBL, MBL and Carbapenemase production were performed as per the Clinical and Laboratory Standards Institute (CLSI). The Modified Hodge test (MHT) was performed for Carbapenemase production detection in Acinetobacter species. A total of 150 Acinetobacter species were isolated from clinical samples. Acinetobacter baumannii was the most prevalent species 138 (92%), followed by Acinetobacter lwoffii 10 (7%) and Acinetobacter hemolyticus 2 (1%). The isolates showed highest resistance to Ampicillin 130 (87%) and sensitive to Colistin 113 (75.3%). Most of the isolates of of Acinetobacter baumannii showed maximum ESBL 21(14%) and MBL 75 (93%) production. Modified Hodge test showed positive results in Acinetobacter baumannii, only 11 (7%). The study showed that Acinetobacter baumannii was the most prevalent species showing drug resistance by phenotypic detection methods. At present Acinetobacter is a frequent pathogen in hospital acquired infections in critically ill patients admitted to ICU. The isolates of Acinetobacter species in our study showed resistant to most commonly used antibiotics. The study showed that ESBL production in Acinetobacter was 22 (15%) and MBL 80 (53%). Most Acinetobacter isolates were Multi Drug Resistant (MDR). MDR Acinetobacter is widely increasing due to inappropriate use of antibiotics in healthcare hospital. In our study, detection of carbapenemase by Modified Hodge test was positive in 11 (7%) isolates.

Real-world experience with meropenem/vaborbactam for the treatment of infections caused by ESBL-producing Enterobacterales and carbapenem-resistant Klebsiella pneumoniae.

Real-world experience with meropenem/vaborbactam (M/V) is limited. Our aim is to report a clinical experience of M/V in the treatment of resistant Gram-negative bacilli. This is a prospective observational study including patients hospitalized in the University Hospital of Pisa (March 2021-Jan 2023) with infections by both extended-spectrum β-lactamases (ESBL)-producing Enterobacterales and carbapenem-resistant Klebsiella pneumoniae (Kp) treated with M/V. The primary outcome measure was clinical success, defined as a composite of survival, resolution of signs and symptoms and absence of microbiological failure at day 30 from infection onset. A multivariable regression analysis was performed to identify factors associated with clinical failure. Odds ratio (OR) with 95% confidence intervals (CI) was calculated. A total of 104 patients who received M/V were included: 24/104 (23.1%) infections were caused by ESBL non-hypervirulent Enterobacterales, 17/104 (16.3%) by ESBL-producing hypervirulent Klebsiella pneumoniae (hvKp) and 63/104 (60.6%) by CRE. The most common infections were bloodstream infections, followed by urinary tract infections, hospital-acquired pneumonia, intra-abdominal infections and others. Septic shock occurred in 16/104 (15.4%) patients. Clinical success was achieved in 77% of patients, and 30-day mortality rate was 15.4%. In patients with KPC-producing Kp infections, clinical success and 30-day mortality rates were 82% and 11.5%, respectively. On multivariable analysis, SOFA score (OR 1.32, 95% CI 1.02-1.7, p=0.032) was independently associated with clinical failure, while source control (OR 0.16, 95% CI 0.03-0.89, p=0.036) was protective. M/V is a promising therapeutic option against infections caused by difficult-to-treat ESBL-producing Enterobacterales and CR-Kp.

Assessment of BlaTEM, BlaSHV, and BlaCTX-M genes of antibiotic resistance in Gram-negative bacilli causing urinary tract infections in Khartoum State: a cross-sectional study

BackgroundGram-negative bacilli are the most common etiological agents responsible for urinary tract infections. The prevalence of antibiotic resistance in Gram-negative bacilli is increasing at a rapid pace globally, which is constraining the available choices for UTI treatment. The objectives of this study are to identify the most common causal organisms of urinary tract infections (UTIs), and to determine their drug resistance patterns.Materials and methodsThis was a cross-sectional hospital-based study conducted at El-Amal Hospital, Bahri Teaching Hospital, and Al-Baraha Hospital, Khartoum State, from March to October 2022. Urine samples from patients suspected to have UTI were collected, and patients with confirmed UTI by laboratory investigations and yielded culture growth were enrolled. Antibiotic sensitivity testing and PCR testing of the blaTEM, blaSHV, and blaCTX-M genes were done.ResultsThis study included 50 patients with UTI out of 229 suspected patients (21.8%). The most prominent group of patients was older than 60 years (40%); the majority were females (70%). Escherichia coli was the most prevalent isolated organism (50%), followed by Klebsiella oxytoca (24%), Klebsiella pneumoniae (20%), Pseudomonas aeruginosa (4%), and Citrobacter freundii (2%). A small percentage of organisms were resistant to colistin (17%). However, 77% were resistant to amikacin, 97.6% to cefotaxime, 96.8% to ceftazidime, 97.6% to ceftriaxone, 96.8% to cefixime, 87.6% to ciprofloxacin, 88.4% to gentamycin, 62% to imipenem, 67.6% to meropenem, 87.6% to norfloxacin, and 95.6% to trimethoprim. The overall resistance of isolated gram-negative organisms was 81%. The most prevalent gene for the resistance was blaTEM (100%), followed by blaCTX-M (94%), and then blaSHV (84%).ConclusionEscherichia coli and Klebsiella species were the most commonly isolated uropathogens in this study, and the majority were highly resistant to most of the antimicrobial agents tested. Resistance genes blaTEM, blaCTX-M, and blaSHV are very common in uropathogens.

Comparative study of colistin methanesulfonate and colistin sulfate/polymyxin B in the treatment of ceftazidime-avibactam resistant Gram-negative bacilli infections

ObjectiveTo evaluate the clinical efficacy of different species of polymyxin drugs in the treatment of Carbapenem-Resistant Gram-negative bacilli (CR-GNB) resistant to ceftazidime-avibactam (CZA). MethodsPatients infected by CR-GNB strains and treated with polymyxin drugs were selected and divided into colistin methanesulfonate (CMS) group and colistin sulfate/polymyxin B (CSPB) group to observe clinical efficacy and safety. Results65 patients were eventually included (CMS group, n ​= ​29; CSPB group, n ​= ​36). The clinical efficacy, microbiological eradication rate and 28-day mortality between the two groups were similar, with no statistical significance (51.72% vs. 50.00%, p ​= ​0.890; 55.17% vs. 52.78%, p ​= ​0.847; 17.24% vs. 25.00%, p ​= ​0.449). With regard to renal safety, the incidence of acute kidney injury (AKI) in the CMS group was significantly higher than that in the CSPB group (34.48% vs. 5.56%, p ​= ​0.003). Among them, the incidence of AKI grade 3 in the CMS group tended to be higher than that in the CSPB group (24.14% vs. 5.56%, p ​= ​0.066). ConclusionThe results based on small sample size from a single center showed that clinical response to the treatment of ceftazidime-avibactam resistant Gram-negative bacillus infections is similar for CMS and Colistin Sulfate/Polymyxin B, but the nephrotoxicity of CMS is greater than that of polymyxin sulfates.

Detection of Carbapenemase Genes by Molecular Method among Gram-Negative Bacilli Isolates from Tertiary Care Hospital in Dhaka, Bangladesh

Background: Imipenem resistance in Gram-negative bacilli is a global epidemic that is increasing day by day.To warn this global epidemic, identification and ongoing surveillance of carbapenem-resistant genes among Gram-negative bacilli needed.Objectives: This cross-sectional study was performed todetect the imipenem resistant genes among Gram-negative bacilli isolated from different samples in Dhaka medical college hospital.Methods: About 300 samples (wound swab, urine, endotracheal aspirate, blood, and sputum) were collected from July 2015 to June 2016. Among them, 204 isolates were Gram negative bacilli. Eighty imipenem resistant Gram-negative bacilli were isolated by disc diffusion method. Among them, carbapenem resistant genes (blaNDM-1, blaKPC, VIM, IMP) were detected by PCR.Results: A total 300 samples were analyzed. Out of 204 Gram negative bacilli,80 (39.21%) imipenem resistance was detected by the Disc Diffusion method. Out of 80 imipenem resistant organisms, 42 (52.5%) were positive for blaNDM-1, 6 (7.34%) were positive for blaKPC, 29 (36.25%) were positive for VIM, 13 (16.25%) were positive for IMP.Conclusion: This study illustrates the emergence of carbapenemase genes producing Gram negative bacilli isolates from patients. Close surveillance across all hospitals in Bangladesh is required. J Shaheed Suhrawardy Med Coll 2022; 14(1): 3-7

Distribution and antimicrobial resistance analysis of gram-negative bacilli isolated from a tertiary hospital in Central China: a 10-year retrospective study from 2012 to 2021.

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. 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. 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). 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.