Multidrug-resistant Non-fermenting Gram-negative Bacilli Research Articles

In vitro activity of cefiderocol and comparator antibiotics against multidrug-resistant non-fermenting Gram-negative bacilli.

This study evaluated the in vitro activity of cefiderocol, ceftazidime/avibactam, and aztreonam/avibactam against clinically important multidrug-resistant non-fermenting Gram-negative bacilli. Bacteraemic isolates of 126 multidrug-resistant Acinetobacter baumannii (MDRAB), 110 imipenem-resistant Pseudamoas aeruginosa [including 14 difficult-to-treat resistant P. aeruginosa (DTRPA)], 45 beta-lactam-non-susceptible Burkholderia cepacia complex (BCC), 47 levofloxacin or trimethoprim/sulfamethoxazole-non-susceptible Stenotrophomonas maltophilia and 22 ciprofloxacin-non-susceptible Elizabethkingia spp. collected between 2019 and 2021 were subjected to MIC determination for cefiderocol, ceftazidime/avibactam and aztreonam/avibactam. The MIC50/90s of cefiderocol for drug-resistant A. baumannii, P. aeruginosa, BCC, S. maltophilia and Elizabethkingia spp. were 0.25/2, 0.25/1, ≤0.06/≤0.06, ≤0.06/0.25 and >32/>32 mg/L, respectively. Cefiderocol inhibited 94.4% (119/126) of MDRAB, 100% of imipenem-resistant P. aeruginosa, 100% of DTRPA and 100% of BCC at an MIC ≤4 mg/L, and 97.9% (46/47) of S. maltophilia at ≤1 mg/L. Ceftazidime/avibactam inhibited 76.4% (84/110) of imipenem-resistant P. aeruginosa, 21.4% (3/14) of DTRPA and 68.9% (31/45) of BCC at an MIC ≤8 mg/L. Aztreonam/avibactam had MIC50/90s of 16/>32, 8/16 and 4/8 mg/L for imipenem-resistant P. aeruginosa, BCC and S. maltophilia, respectively. At ≤8 mg/L, aztreonam/avibactam inhibited 7.1% (1/14) of DTRPA and 93.6% (44/47) of S. maltophilia isolates. Elizabethkingia spp. demonstrated high MICs for cefiderocol, ceftazidime/avibactam and aztreonam/avibactam, with all MIC50s and MIC90s > 32 mg/L. Cefiderocol may serve as an alternative treatment for multidrug-resistant A. baumannii, P. aeruginosa, BCC and S. maltophilia when other antibiotics have been ineffective or intolerable. The role of ceftazidime/avibactam and aztreonam/avibactam in the management of BCC or S. maltophilia infections warrants further investigation.

Whole-Genome Sequencing-Based Resistome Analysis of Nosocomial Multidrug-Resistant Non-Fermenting Gram-Negative Pathogens from the Balkans

Non-fermenting Gram-negative bacilli (NFGNB), such as Pseudomonas aeruginosa and Acinetobacter baumannii, are among the major opportunistic pathogens involved in the global antibiotic resistance epidemic. They are designated as urgent/serious threats by the Centers for Disease Control and Prevention and are part of the World Health Organization's list of critical priority pathogens. Also, Stenotrophomonas maltophilia is increasingly recognized as an emerging cause for healthcare-associated infections in intensive care units, life-threatening diseases in immunocompromised patients, and severe pulmonary infections in cystic fibrosis and COVID-19 individuals. The last annual report of the ECDC showed drastic differences in the proportions of NFGNB with resistance towards key antibiotics in different European Union/European Economic Area countries. The data for the Balkans are of particular concern, indicating more than 80% and 30% of invasive Acinetobacter spp. and P. aeruginosa isolates, respectively, to be carbapenem-resistant. Moreover, multidrug-resistant and extensively drug-resistant S. maltophilia from the region have been recently reported. The current situation in the Balkans includes a migrant crisis and reshaping of the Schengen Area border. This results in collision of diverse human populations subjected to different protocols for antimicrobial stewardship and infection control. The present review article summarizes the findings of whole-genome sequencing-based resistome analyses of nosocomial multidrug-resistant NFGNBs in the Balkan countries.

OCCURRENCE OF NON-FERMENTATIVE GRAM-NEGATIVE BACILLI AND THEIR DRUG RESISTANCE IN TERTIARY CARE RURAL HOSPITAL IN LONI, ( M.S.)

Background: Aerobic non-fermenting Gram-negative bacilli (NF-GNB) once consider as a contaminant now associated with life-threatening infection and emerging as multi drug resistant nosocomial pathogens. Aim: Isolation and identication of NF-GNB in all the clinical samples and to determine antibiotic susceptibility pattern of the isolated NF-GNB. Materials And Methods: This study has been conducted in the Department of Microbiology at a tertiary care teaching hospital over a period of one year. NFGNB were isolated and identied from clinical samples by standard procedure and antibiotic sensitivity was performed (according to CLSI guidelines). Out of 1498 clinical specimens, 320 (21.36%) isolates were identied as NF-GNB. Maximu Results: m number of was blood, 90 (28.12%) followed by pus, 84 (26.25%), Pseudomonas Aeruginosa was the commonest isolate, 192 (60%), followed by Pseudomonas species, 58(18.12%) & Acinetobacter boumannii, 46(14.37%). All isolates most of them MDR and were sensitive to polymyxin B, colistin and tigecycline. Multi drug resistant NF-GNB was not uncommon in our hospital. All Conclusion: isolates were sensitive to polymyxin B, colistin and tigecycline. Indiscriminate use of antibiotics against these organisms should be avoided. It is necessary to identify NFGNB & to monitor their susceptibility pattern to guide the clinician for better care and management of patients.

832. Assessment of Risk Factors Associated with Wide-resistance Gram-negative Bacteria Infections

BackgroundEnterobacteria and multidrug-resistant non-fermenting Gram-negative bacilli present a challenge in the management of invasive infections, leading to mortality rates due to their limited therapeutic arsenal. The objective of this work was to analyze risk factors that may be associated with these infections, for a better situational mapping and assertive decision-making in a university hospital in Brazil.MethodsThe study was conducted between January and September 2019, with 167 patients in contact isolation at a university hospital in Brazil. Potential outcome-related variables for wide-resistance Gram-negative bacteria (BGN) infections were evaluated. Risk factors were identified from univariate statistical analysis using Fisher’s test.Results51 (30.5%) out of 167 patients in contact isolation evolved with wide-resistance BGN infection. Risk factors in univariate analysis were age, hospital unit and previous use of invasive devices. Patients aged up to 59 years were more likely to progress to infection than those aged over 60 years (p 0.0274, OR 2.2, 95% CI 1.1-4.5). Those admitted to the oncohematology (p < 0.001, OR 32.5, Cl 9.1-116.3) and intensive care unit (p < 0.001, OR 28.0, Cl 3.5-225.9) units were more likely to develop this type of infection. The least likely were those admitted to a kidney transplant unit (p 0.0034, OR 15.33, Cl 1.8-131.0). Prior use of mechanical ventilation (p 0.0058, OR 12.2, Cl 2.0-76.1) and delayed bladder catheter (p 0.0266, OR 5.0, Cl 1.2-20.1) in patients with respiratory and urinary tract infection, respectively, were also reported as risk factors related to these infections. The gender of the patients was not significant for the study.ConclusionThis study determined that variables such as age, hospitalization unit, use of mechanical ventilation and delayed bladder catheter could be considered important risk factors in triggering the infectious process by wide-resistant gram-negative bacteria. Thus, the analysis of these factors becomes a great foundation to prevent the development of multiresistant pathogens through prevention strategies, prophylaxis management and more targeted empirical therapies.Disclosures All Authors: No reported disclosures

In vitro activity of β-lactams in combination with avibactam against multidrug-resistant Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Achromobacter xylosoxidans isolates from patients with cystic fibrosis.

The in vitro activity of anti-pseudomonal β-lactams in combination with avibactam was evaluated against 54 multidrug-resistant non-fermenting Gram-negative bacilli isolated from cystic fibrosis patients. Avibactam increased and/or restored the antibacterial activities of ceftazidime and aztreonam against Pseudomonas aeruginosa and Stenotrophomonas maltophilia, respectively. No β-lactam-avibactam combination was active against Achromobacter xylosoxidans.

Meropenem and Vaborbactam: Stepping up the Battle against Carbapenem-resistant Enterobacteriaceae.

Vaborbactam (VAB; formerly RPX7009) is a novel beta-lactamase inhibitor based on a cyclic boronic acid pharmacophore with potent inhibitory activity against Ambler class A and C beta-lactamases. It has been co-formulated with meropenem to restore its activity against Klebsiella pneumoniae carbapenemases (KPC). VAB does not inhibit class B or D carbapenemases, nor does it improve the activity of meropenem against multidrug-resistant nonfermenting gram-negative bacilli, notably Acinetobacter spp. and Pseudomonas aeruginosa. The purpose of this article is to review existing data pertaining to the biochemistry, mechanism of action, pharmacokinetics/pharmacodynamics, invitro activity, and current progress in clinical trials of meropenem and VAB (MV). Phase 1 studies have demonstrated single and multiple doses of VAB up to 2000mg, alone or in combination with meropenem 2000mg administered as a prolonged infusion over 3hours, are well tolerated with an adverse effect profile similar to that of meropenem monotherapy. The available data suggest preexisting resistance among KPC-producing isolates is rare. Strains with elevated MICs have been characterized by multiple resistance determinants including porin defects, increased drug efflux, and increased blaKPC expression. It remains uncertain whether multifactorial resistance will emerge during MV treatment and with more widespread use. Early data are positive for complicated urinary tract infections and MV compared with best available therapy in patients with serious carbapenem-resistant Enterobacteriaciae (CRE) infections. As clinicians contemplate how to incorporate MV into CRE treatment strategies, it will be important to track and understand resistance, discern the role, if any, of combination therapy in enhancing efficacy and/or preserving activity, and define the specific therapeutic niche of MV among the expanding anti-CRE armamentarium.

In Vitro Activity of Ceftolozane-Tazobactam against Multidrug-Resistant Nonfermenting Gram-Negative Bacilli Isolated from Patients with Cystic Fibrosis.

Ceftolozane-tazobactam was tested against 58 multidrug-resistant nonfermenting Gram-negative bacilli (35 Pseudomonas aeruginosa, 11 Achromobacter xylosoxydans, and 12 Stenotrophomonas maltophilia isolates) isolated from cystic fibrosis patients and was compared to ceftolozane alone, ceftazidime, meropenem, and piperacillin-tazobactam. Ceftolozane-tazobactam was the most active agent against P. aeruginosa but was inactive against A. xylosoxydans and S. maltophilia In time-kill experiments, ceftolozane-tazobactam had complete bactericidal activity against 2/6 clinical isolates (33%).

Presence of metallo-beta-lactamases (MBL), extended-spectrum beta-lactamase (ESBL) & AmpC positive non-fermenting Gram-negative bacilli among Intensive Care Unit patients with special reference to molecular detection of blaCTX-M & blaAmpC genes.

Background & objectives:Non-fermenting Gram-negative bacilli (NFGNB) including Pseudomonas aeruginosa and Acinetobacter baumannii have been implicated in a variety of infections, particularly in the Intensive Care Units (ICUs). This study was aimed to overview the burden of multidrug-resistant NFGNB causing infections in ICU and also to assess the occurrence of extended-spectrum beta-lactamases (ESBLs), AmpC and metallo-beta-lactamases (MBLs) among these isolates.Methods:Bacterial culture, identification and antibiotic susceptibility were carried out. ESBLs and AmpC were detected both phenotypically and genotypically. MBL was detected by modified Hodge and imipenem-ethylenediaminetetraacetic acid double-disc synergy test.Results:NFGNB represented 45 (37%) of total 121 Gram negative isolates. Multidrug resistance was observed in 66.9 per cent and 72.5 per cent isolates of P. aeruginosa and A. baumannii, respectively. Detection by phenotypic methods showed presence of ESBL, AmpC and MBL in 21.4, 51.1 and 21.4 per cent isolates, respectively. When detected genotypically by polymerase chain reaction, ESBL and AmpC were detected in 21.4 and 41.4 per cent of NFGNB isolates, respectively. BlaCTX-M (21.4%) was the most prevalent gene responsible for ESBL production.Interpretation & conclusions:Most of the NFGNB isolated from ICU patients were multidrug-resistant and producers of ESBL, AmpC and MBL. A regular surveillance is required to detect ESBL, AmpC and MBL producers, especially in ICU patients.

Antibiotic resistance profile of non-fermenting Gram-negative bacilli isolated from the blood cultures of cancer patients.

Sir, Non-fermenting Gram-negative bacilli (NFGNB) are a group of organisms that either do not utilize glucose as a source of energy or utilize it oxidatively. NFGNB can cause a significant number of infections, ranging from superficial to deep-seated and disseminated infections in immunocompromised hosts, neutropenic patients, patients with cystic fibrosis, patients on mechanical ventilation and indwelling catheters, and patients undergoing invasive diagnostic and therapeutic procedures. Blood stream infections (BSI) caused by NFGNB are a major cause of morbidity and mortality worldwide. High intrinsic resistance of NFGNB to antimicrobial compounds makes the treatment of BSIs caused by them difficult and expensive. NFGNB have a varied isolation rate, ranging from 2.18 to 45.9%, as observed from various clinical samples.[1] In an attempt to recognize the antibiotic resistance and prevalence pattern among NFGNB associated with BSIs in cancer patients, a prospective study was conducted over a period of one year from July 2013 to June 2014, at a tertiary care cancer institute in North India. Blood culture was performed in BacT/Alert blood culture bottles (bioMerieux, Durham, North Carolina, USA). From the positive bottles, the subcultures were performed on MacConkey agar and blood agar. The VITEK®2 Compact (C) system (bioMerieux, North Carolina, USA) was used to identify NFGNB up to the species level, using the Gram-negative Identification (GN-ID) 21341 card, and antibiotic susceptibility testing (AST) was done using the AST 281 card. The antibiotic susceptibility results were expressed as susceptible, intermediate or resistant, according to the criteria of the Clinical Laboratory Standards Institute (CLSI) M100-S23 (2013).[2] Among 815 total samples received for blood culture, 249 bottles were flagged as positive in the BacT Alert 3D. However, only 172 yielded pathogenic bacteria on subculture. Sixty-three (36.6%) were Gram-negative and 108 (62.7%) were Gram-positive organisms, while one isolate was fungus (Candida sp.). Forty, out of 63 (63.5%) Gram-negative organisms were NFGNB, out of which Burkholderia cepacia (60%) was the predominant isolate. Acinetobacter baumannii (20%), Pseudomonas aeruginosa (12.5%), Pseudomonas stutzeri (2.5%), Alcaligenes faecalis (2.5%), and Sphingomonas paucimobilis (2.5%) were the other NFGNB isolated from the blood stream infections. The antibiotic susceptibility results are given in Table 1, which shows the percentage of resistant isolates. A high level of resistance against the first- and second-line antibiotics was noted. In this study, NFGNB were isolated from 4.9% of the total blood samples received for the culture. Out of the total Gram-negative bacilli, the NFGNB in our study were 63.5% (40/63), and B. cepacia was the predominant NFGNB. Prabash et al., in 2010, analyzed the blood cultures of cancer patients (neutropenic and non-neutropenic) and found that non-fermenters comprised a majority of the Gram-negative bacilli isolated (62.24%), with Pseudomonas (30.37%) and Acinetobacter sp. (11.57%) being the predominant NFGNBs.[3]Table 1: Antibiotic resistance pattern (percentage) of NFGNB isolated from blood cultureThe in vitro anti-microbial susceptibility of Burkholderia cepacia isolates revealed 92% resistance to meropenem, while the susceptibility to co-trimoxazole was 100%. The 2010 Sanford Guide recommends co-trimoxazole as the treatment of choice for these infections. The other antibiotics to which B. cepacia isolates are susceptible are meropenem, ceftazidime, ceftibuten, chloramphenicol, and trimethoprim.[4] However, according to literature, the antibiogram of B. cepacia isolates from cancer patients may be slightly different, with increased susceptibility to some antibiotics, especially piperacillin, piperacillin-tazobactam, and cefepime.[56] One hundred and 87.5% of A. baumannii isolates were resistant to aminoglycosides and colistin, respectively, while all the isolates were susceptible to meropenem. Among the Pseudomonas species, a high level of resistance was recorded for ceftazidime (50%), aztreonam (50%), and doripenem (50%). Colistin and cefepime showed maximum activity with an overall susceptibility of 100 and 83.3%, respectively. A single isolate of A. faecalis (2.5%) was resistant to all antibiotics, except amikacin. However, S. paucimobilis (2.5%) was a fairly sensitive strain, with resistance observed only against ceftazidime and aztreonam. The emerging challenges of multidrug resistance, both intrinsic and acquired, among NFGNB, are of serious concern to the treating physician. Improved antibiotic stewardship and infection control measures will be needed to prevent or slow down the emergence and spread of multidrug-resistant NFGNB in the healthcare setting. Identification of NFGNB and monitoring their susceptibility patterns will help in improving the empirical therapy.

Prevalence of non-fermenting Gram-negative bacilli and their in vitro susceptibility pattern at a tertiary care teaching hospital

Background: Aerobic non-fermenting Gram-negative bacilli (NFGNB) once considered as contaminants now associated with life-threatening infections and emerging as multi drug resistant nosocomial pathogens. Aim: Isolation and identification of NFGNB in all the clinical samples and to determine antibiotic susceptibility pattern of the isolated NFGNB. Materials and Methods: This study has been conducted in the Department of Microbiology at a tertiary care teaching hospital over a period of 2 months from September to October 2013. NFGNB were isolated and identified from clinical specimens by standard procedure and antibiotic sensitivity test was performed. Results: NFGNB isolation rate in the present study was 3.58%. Male to female ratio was 2.125. Pus was the most common specimen (21%) followed by tracheal aspirate (17%). Pseudomonas aeruginosa was the most common isolate (60%) followed by Acinetobacter baumannii (22%) and Acinetobacter lwoffii (12%). P. aeruginosa has shown good sensitivity to amikacin (83.3%), imipenem (80%) and piperacillin-tazobactam (73.3%) whereas A. baumannii showed multidrug resistance. Conclusion: It is necessary to identify NFGNB and to monitor their susceptibility pattern to guide the clinician for better care and management of patients. NFGNB are now emerging as organisms of nosocomial infections. Hence, antibiotic sensitivity testing and infection control measures are needed to prevent the emergence and spread of multi drug resistant NFGNB in health care settings.

Evaluation of three phenotypic methods for the detection of metallo-beta- lactamase production in non fermenting gram negative bacilli

Background & objectives: Non-fermenting gram-negative bacilli (NFGNB) are common nosocomial pathogens and are often resistant to several antibiotics in clinical practice. Metallo-beta-lactamase (MBL) mediated resistance to carbapenems is an emerging threat among hospital isolates of P.aeruginosa. As there are no CLSI guidelines for the detection of these enzymes the present study was conducted with the objective to evaluate three phenotypic methods for the detection of Carbapenemase and MBL production in NFGNB. Methods: 100 consecutive NFGNB resistant to ceftazidime and imepenem by disc diffusion test were included in the study. Resistance to imepenem was confirmed by determining the minimum inhibitory concentration (MIC) by agar dilution method. Three phenotypic tests, namely modified Hodge test (MHT), ethylene di-amine tetra acetic acid (EDTA) imepenem double disk synergy test (DDST) and 4-fold reduction in MIC with imipenem-EDTA combination were evaluated for detection of carbapenemase and MBL production. Results: Of the 100 multidrug resistant NFGNB isolated 66 were P. aeruginosa and 34 were Acinetobacter species. 62 P.aeruginosa and 31 Acinetobacter isolates were confirmed resistant to imepenem by MIC, 7 isolates had MIC values in the intermediate range. 55/100 imepenem resistant isolates were MBL producers by MHT. 73/100 isolates were positive for MBL production by DDST. 74/100 isolates showed more than fourfold fall in MIC with IMP-EDTA combination. In this study 74% of imepenem resistant NFGNB were MBL producers. Interpretation & Conclusion: P.aeruginosa was the predominant NFGNB isolated. DDST and MIC with imipenem EDTA combination are almost equally effective and more sensitive than MHT for detection MBL production. Routine screening for MBL mediated carbapenem resistance among clinical isolates of NFGNB is important to ensure appropriate treatment of infections caused by them in clinical settings.

Prevalence of non-fermenting gram negative bacilli and their in vitro susceptibility pattern in a tertiary care hospital of Uttarakhand: A study from foothills of Himalayas

Introduction: Non-fermenting gram negative bacilli (NFGNB) are taxonomically diverse group of pathogens that has emerged as a major cause of health care associated infections especially in immunocompromised hosts. Identification of NFGNB and monitoring their susceptibility pattern are important for proper management of infections caused by them. Prevalence and antibiogram of NFGNB has not yet been reported from this part of India. Aim of the present study was to characterize the prevalence of NFGNB along with their antimicrobial sensitivity pattern among the patients coming to our hospital a tertiary care center. Materials and Methods: A total of 2585 various clinical specimens were received in laboratory and were processed. Non fermenters were identified using a standard protocol. Antimicrobial susceptibility testing was performed by Kirby Bauer disc diffusion method. Results: Among 2585 clinical samples 241 yielded NFGNB accounting for an isolation rate of 9.32% and a total of 246 non fermenters were grown as five samples yielded two types of NFGNB. Pseudomonas species (49.59%) and Acinetobacter species (43.09%) were the most commonly isolated NFGNB. A high level of antibiotic resistance was recorded for most of the first and second line drugs. Imipenem and amikacin were the drugs with maximum activity. Overall imipenem resistance was found to be 30.54%. Conclusion: Identification of NFGNB and monitoring their susceptibility patterns will help in proper management of infections caused by them. Improved antibiotic stewardship and infection-control measures will be needed to prevent or slow the emergence and spread of multidrug-resistant NFGNB in the healthcare setting.

Fosfomycin for the treatment of infections caused by multidrug-resistant non-fermenting Gram-negative bacilli: a systematic review of microbiological, animal and clinical studies

The treatment of multidrug-resistant (MDR), extensively drug-resistant or pandrug-resistant non-fermenting Gram-negative bacterial infections constitutes a challenge in an era of few new antibiotic choices. This mandates the re-evaluation of already existing antibiotics such as fosfomycin. We systematically reviewed the literature to assess the clinical and microbiological effectiveness of fosfomycin in the treatment of these infections by searching PubMed, Scopus and the Cochrane Library databases. In 23 microbiological studies identified, 1859 MDR non-fermenting Gram-negative bacterial isolates were examined. The susceptibility rate to fosfomycin of MDR Pseudomonas aeruginosa isolates was ≥90% and 50–90% in 7/19 and 4/19 relevant studies, respectively. Cumulatively, 511/1693 (30.2%) MDR P. aeruginosa isolates were susceptible to fosfomycin. Serotype O12 isolates exhibited greater susceptibility. Only 3/85 (3.5%) MDR Acinetobacter baumannii and 0/31 MDR Burkholderia spp. isolates were susceptible to fosfomycin. Variable criteria of susceptibility were used in the included studies. Fosfomycin was synergistic in combination with a β-lactam, aminoglycoside or ciprofloxacin in 46/86 (53.5%) MDR P. aeruginosa isolates. One animal study found a good therapeutic effect of the combination fosfomycin/gentamicin against MDR P. aeruginosa endocarditis. In six clinical studies, 33 patients with MDR P. aeruginosa infections (mainly pulmonary exacerbations of cystic fibrosis) received fosfomycin (25/33 in combination with other antibiotics); 91% of the patients clinically improved. In conclusion, fosfomycin could have a role as a therapeutic option against MDR P. aeruginosa infections. Further research is needed to clarify the potential utility of this agent.