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Background: Colistin is a last-resort antibiotic used in extreme cases of multi-drug resistant (MDR) Gram-negative bacterial infections. Colistin resistance has increased in recent years and often goes undetected due to the inefficiency of predominantly used standard antibiotic susceptibility tests (AST). To address this challenge, we aimed to detect the prevalence of colistin resistance strains through both Vitek®2 and broth micro-dilution. We investigated 1748 blood, tracheal aspirate, and pleural fluid samples from the Intensive Care Unit (ICU), Neonatal Intensive Care Unit (NICU), and Tuberculosis and Respiratory Disease centre (TBRD) in an India hospital. Whole-genome sequencing (WGS) of extremely drug-resitant (XDR) and pan-drug resistant (PDR) strains revealed the resistance mechanisms through the Resistance Gene Identifier (RGI.v6.0.0) and Snippy.v4.6.0. Abricate.v1.0.1, PlasmidFinder.v2.1, MobileElementFinder.v1.0.3 etc. detected virulence factors, and mobile genetic elements associated to uncover the pathogenecity and the role of horizontal gene transfer (HGT). Results: This study reveals compelling insights into colistin resistance among global high-risk clinical isolates: Klebsiella pneumoniae ST147 (16/20), Pseudomonas aeruginosa ST235 (3/20), and ST357 (1/20). Vitek®2 found 6 colistin-resistant strains (minimum inhibitory concentrations, MIC = 4 μg/mL), while broth microdilution identified 48 (MIC = 32–128 μg/mL), adhering to CLSI guidelines. Despite the absence of mobile colistin resistance (mcr) genes, mechanisms underlying colistin resistance included mgrB deletion, phosphoethanolamine transferases arnT, eptB, ompA, and mutations in pmrB (T246A, R256G) and eptA (V50L, A135P, I138V, C27F) in K. pneumoniae. P. aeruginosa harbored phosphoethanolamine transferases basS/pmrb, basR, arnA, cprR, cprS, alongside pmrB (G362S), and parS (H398R) mutations. Both strains carried diverse clinically relevant antimicrobial resistance genes (ARGs), including plasmid-mediated blaNDM-5 (K. pneumoniae ST147) and chromosomally mediated blaNDM-1 (P. aeruginosa ST357). Conclusion: The global surge in MDR, XDR and PDR bacteria necessitates last-resort antibiotics such as colistin. However, escalating resistance, particularly to colistin, presents a critical challenge. Inefficient colistin resistance detection methods, including Vitek2, alongside limited surveillance resources, accentuate the need for improved strategies. Whole-genome sequencing revealed alarming colistin resistance among K. pneumoniae and P. aeruginosa in an Indian hospital. The identification of XDR and PDR strains underscores urgency for enhanced surveillance and infection control. SNP analysis elucidated resistance mechanisms, highlighting the complexity of combatting resistance. [ABSTRACT FROM AUTHOR]

Background and Objectives: Over the last decade, hospital-acquired infections, particularly in the critical care setting, have become more common, with Gram-negative bacterial infections having the highest prevalence. This study aims to determine the prevalence and antibiotic susceptibility pattern of Pseudomonas species to WHO's, aware class of antibiotics, which are commonly prescribed across various ICU's, medical and surgical wards of our tertiary care teaching hospital. Materials and Methods: This prospective study conducted from January 2021 to June 2022 at a tertiary care centre of central India identified Pseudomonas species from clinical samples using standard procedures and antimicrobial susceptibility testing performed as per Clinical Laboratory Standards Institute (CLSI) guidelines (M100; 32th Edition). Results: A total of 1490 non duplicate Pseudomonas species isolates were grown from 21,019 culture positive clinical samples, of which 1247 were Pseudomonas aeruginosa. Out of these 1247 Pseudomonas aeruginosa 384 were MDR (30.7%). Pseudomonas aeruginosa were most commonly isolated from the pus samples (85%). ICU isolates were significantly more resistant to antibiotics than those from other units. P. aeruginosa strains from ICUs showed the highest rates of resistance to ceftazidime (93.9%). Reserve drug colistin showed good susceptibility (98.2%). All the 18 colistin resistant strains were found to be negative for plasmid mediated mcr-1,2,3 genes. Conclusion: The study shall help to generate and disseminate the data so that proper antibiotic policy can be made for judicious use of Access, Watch and Reserve antibiotics and antibiotic de-escalation plan can be put forth. [ABSTRACT FROM AUTHOR]

Background: Intensive care units have become hotspots for antimicrobial resistance, particularly concerning colistin resistance, posing a threat of untreatable infections. Aim: This study aims to analyze the epidemiological and clinical aspects of patients carrying colistin-resistant organisms. It focuses on identifying risk factors, the microbiological profile, susceptibility patterns, and treatment outcomes. Materials and methods: Isolates with colistin MIC >2 µg/mL, identified via BD PHOENIX, were subjected to colistin broth disc elution testing (as per CLSI guidelines) in our Microbiology Department between January and December 2022. Results: Among the 30 patients, colistin-resistant gram-negative isolates were found predominantly in blood cultures (50%), followed by ET/ TT cultures (23.3%), urine cultures (10%), and other sites (16.7%). Klebsiella pneumoniae was the most common organism (80%), showing the highest sensitivity to Ceftazidime-avibactam + Aztreonam (CAZ-AVI + ATM) (76.7%). Of these patients, 66.7% recovered and were discharged, while 33.3% succumbed during hospitalization despite treatment. Conclusion: The study underscores a notable presence of colistin-resistant gram-negative isolates, predominantly in blood cultures, with K. pneumoniae being predominant. The combination of CAZ-AVI + ATM exhibited the highest sensitivity. However, the mortality rate of 33.3% despite sensitive antibiotic treatment highlights the urgency for ongoing vigilance and research to combat colistin-resistant infections and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Increasing prevalence of carbapenem resistance among Enterobacterales, particularly Escherichia coli and Klebsiella pneumoniae, poses a serious public health threat globally. Furthermore, these bacteria exhibit multidrug resistance, making treatment of infections caused by them challenging. Colistin is one of the antibiotics used in the treatment of infections caused by carbapenem resistant Enterobacterales; however, its unrestricted usage has resulted in the emergence of colistin resistant strains. The present study was conducted to determine the prevalence of carbapenem resistance and co‑resistance to carbapenem and colistin resistance among E. coli and K. pneumoniae isolated from various clinical specimens from patients attending various departments of a multispecialty teaching hospital in Haryana, India. Methods: A total of 597 isolates comprising 425 E. coli and 172 K. pneumoniae isolated between March 2019 to November 2021 were included in the study. The isolates were subjected to screening for the detection of carbapenemase production using carbapenem discs and a phenotypic test, that is, the CarbaNP test. Antibiogram of the carbapenem‑resistant isolates was further analyzed by the Kirby–Bauer disc diffusion method and to evaluate colistin resistance, isolates were subjected to colistin broth disc elution test. Results: The prevalence of carbapenemase production among the E. coli and K. pneumoniae isolates by the screening test were detected to be 98/425 (23.1%) for E. coli and 90/172 (52.3%) for K. pneumoniae, whereas the CarbaNP test confirmed 93/425 (21.9%) and 84/172 (48.8%) of the two categories of bacterial isolates, thus showing a false positivity rate of 2.6% (n = 11) by screening test for the detection of carbapenemase production. Among the bacterial isolates, 3 (1.7%) comprising 1 (1.1%) E. coli and 2 (2.6%) K. pneumoniae were found to be dual carbapenem‑ and colistin‑resistant strains. K. pneumoniae isolates showed higher resistance rates to non‑carbapenem antibiotics compared to E. coli isolates. Conclusions: The emergence of bacteria with concurrent resistance to carbapenems and colistin is a serious concern as they are the last‑resort drugs against multidrug‑resistant and extensively drug‑resistant bacteria. [ABSTRACT FROM AUTHOR]

Background: Carbapenem-resistant enterobacteriaceae (CRE) is associated with high mortality in critically ill patients, with limited treatment options. This study aims to compare clinical response, microbiological response, and mortality in patients treated with ceftazidime--avibactam with or without aztreonam (CAZ-AVI + AZT) and colistin or polymyxin B (polymyxins) in CRE infections. Materials and methods: This single-center prospective observational study included adult patients with CRE infections treated with CAZ-AVI+AZT or polymyxins between January 2022 and December 2022 at a Tertiary Care Medical Center in India. The clinical response, microbiological response, and mortality were compared between the two groups using a Cox multivariate regression model adjusted for the baseline SOFA score and comorbidities. Results: A total of 89 patients were enrolled, with 59 (66%) patients receiving CAZ-AVI + AZT and 30 receiving polymyxins. Baseline demographics and clinical characteristics were similar between the two groups. The Cox multivariate regression analysis showed a statistically significant difference in clinical failure on day 14 with the CAZ-AVI + AZT group vs polymyxins (HR = 0.78, 95% CI 0.63-0.95, p = 0.018). There was no difference in microbiological failure (HR = 1.08, 95% CI 0.66-1.77, p = 0.76), microbiological relapse (HR = 0.75, 95% CI 0.36-3.02, p = 0.62), and hospital mortality (HR = 1.04, 95% CI 0.75-1.43, p = 0.796) between the two groups. Conclusion: Treatment with ceftazidime--avibactam with or without aztreonam for CRE infections associated with a better clinical response compared with polymyxins monotherapy but without any difference in microbiological response or mortality. [ABSTRACT FROM AUTHOR]

In India, ESBL & Cabapenems producerKlebsiella pneumoniae is treated by Colistin. Recently, Antimicrobial resistance to Colistindue to plasmid resistance is rapidly increasing is a matter of concern. The aim of this study is to evaluate the phenotypic assays for the detection of colistin resistance in Klebsiella pneumoniae isolates from critical care units. Department of Microbiology and Medicine carried out this research at RMCH&RC, Kanpur for 1year between November 2021 to November 2022.Clinical samples from CCU, were collected and processed by standard procedures to isolate and identify Klebsiella pneumoniae. We evaluated Disk diffusion method by Kirby baur’s method, Vitek 2, and standard broth micro dilution (BMD) method. Susceptibility category concordance is the proportion of test results falling into the same category as BMD. Minimal inhibitory concentrations (MIC) concordance was calculated similarly, but taking into account a 1 MIC titre error range. Of 100 isolates, highest MIC concordance to colistin was achieved by Broth micro dilution (23%), followed by Vitek 2® (21%) and detection by Disk diffusion - Kirby baures method, colistin resistance was (40%). Highest susceptibility category concordance to other antibiotics was achieved by Disk diffusion method (60 %) followed by Vitek 2® (79%) and Broth micro dilution (77%). In conclusion, highest MIC concordance was achieved by Broth micro dilution (23%), we found detection of colistin resistance in Klebsiella pneumoniae species by Broth Micro Dilution (BMD) is more reliable method as compared to others. [ABSTRACT FROM AUTHOR]

During the period of COVID‐19, the occurrences of mucormycosis in immunocompromised patients have increased significantly. Mucormycosis (black fungus) is a rare and rapidly progressing fungal infection associated with high mortality and morbidity in India as well as globally. The causative agents for this infection are collectively called mucoromycetes which are the members of the order Mucorales. The diagnosis of the infection needs to be performed as soon as the occurrence of clinical symptoms which differs with types of Mucorales infection. Imaging techniques magnetic resonance imaging or computed tomography scan, culture testing, and microscopy are the approaches for the diagnosis. After the diagnosis of the infection is confirmed, rapid action is needed for the treatment in the form of antifungal therapy or surgery depending upon the severity of the infection. Delaying in treatment declines the chances of survival. In antifungal therapy, there are two approaches first‐line therapy (monotherapy) and combination therapy. Amphotericin B (1) and isavuconazole (2) are the drugs of choice for first‐line therapy in the treatment of mucormycosis. Salvage therapy with posaconazole (3) and deferasirox (4) is another approach for patients who are not responsible for any other therapy. Adjunctive therapy is also used in the treatment of mucormycosis along with first‐line therapy, which involves hyperbaric oxygen and cytokine therapy. There are some drugs like VT‐1161 (5) and APX001A (6), Colistin, SCH 42427, and PC1244 that are under clinical trials. Despite all these approaches, none can be 100% successful in giving results. Therefore, new medications with favorable or little side effects are required for the treatment of mucormycosis. [ABSTRACT FROM AUTHOR]

Background Antimicrobial resistance poses a significant threat to public health globally. We studied the prevalence of colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE), carbapenem-resistant Enterobacterales (CRE), and colistin-resistant Enterobacterales (Col-RE) in hospitals and the surrounding community in South India. Methods Adults from 2 hospitals and the catchment community who consented to provide stool specimens were enrolled. Stools were plated on CHROMagar selective for ESCrE, CRE, and Col-RE. Bacterial identification and antibiotic susceptibility testing were done using Vitek 2 Compact and disc diffusion testing. Colistin broth microdilution was performed for a subset of isolates. Prevalence estimates were calculated with 95% confidence intervals (CIs), and differences were compared across populations using the Pearson χ 2 or Fisher exact test. Results Between November 2020 and March 2022, 757 adults in the community and 556 hospitalized adults were enrolled. ESCrE colonization prevalence was 71.5% (95% CI, 68.1%–74.6%) in the community and 81.8% (95% CI, 78.4%–84.8%) in the hospital, whereas CRE colonization prevalence was 15.1% (95% CI, 12.7%–17.8%) in the community and 22.7% (95% CI, 19.4%–26.3%) in the hospital. Col-RE colonization prevalence was estimated to be 1.1% (95% CI,.5%–2.1%) in the community and 0.5% (95% CI,.2%–1.6%) in the hospital. ESCrE and CRE colonization in hospital participants was significantly higher compared with community participants (P <.001 for both). Conclusions High levels of colonization with antibiotic-resistant Enterobacterales were found in both community and hospital settings. This study highlights the importance of surveillance of colonization in these settings for understanding the burden of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Background: The diminishing antimicrobial options for the treatment of XDR and PDR Acinetobacter baumannii is an increasing concern. In this study, we assessed the in vitro synergy of the fosfomycin (FOS) with meropenem (MEM), amikacin (AK), tigecycline (TGC), and colistin (CL) in whole genome sequenced isolates. Methods: Non-replicate whole genome sequenced (illumina next-generation sequencing platform, Clevergene, India), A. baumanii (7 XDR, 1PDR) were subjected to in vitro synergy testing by checkerboard (CB) and time kill assay (TKA) after MIC determination, with glucose-6-phosphate being incorporated in all runs. FOS was used as a cornerstone drug in four combinations and colistin in one. ResFinder, MLST, PlasmidFinder, and CSIPhylogeny tools were used. Results: Mortality occurred in three patients. Diverse MLST were observed, ST-1962 (3 isolates) and one each of ST2062, ST2063, ST1816, ST1806, ST234. FOS MICs ranged from 32 to 128 mg/L, MEM MIC: 16–64 mg/L, TGC MIC: ≤2–≤4 mg/L and AK MIC: >512 mg/L. CL: MIC range, 0.25–≤2 mg/L, PDR MIC > 16 mg/L. Synergy results by CB: FOS-MEM: synergy in ⅞ (90%) isolates. Synergy lowered MEM MICs to susceptibility breakpoints in 6/8 cases. CL-MEM: Excellent synergy (3/3) isolates. FOS-AK: Indifference in ⅞, antagonism ⅛ (AK-susceptible isolate). FOS-TGC: Partial synergy (PS) in 8/8 (TGC MIC dropped to ≤0.25 mg/L in 3/8). In the PDR isolate, synergy was seen in FOS-MEM, CL-MEM, PS in FOS-CL, FOS-TGC, indifference in FOS-AK. TKA: Excellent synergy was observed with FOS-MEM from 4 h, while FOS-AK and FOS-TGC demonstrated synergy at 24 h. Synergy was achieved despite presence of widespread resistance markers against aminoglycosides (AacAad, AadA, AadB, Aph3″Ia, ArmA, Arr, StrA, StrB), beta-lactams (ADC, BlaA1, BlaA2, Zn-dependent_hydrolase, OXA-23, OXA-51, PER-1,TEM-1D, CARB-5, Mbl), sulphonamides (SulII, SulI), phenicols (CatBx, CmlA), macrolides (MphE, MsrE) and tetracycline (TetB) were widespread. Carbapenemase, CARB-5 was present in one isolate. Beta-lactamase genes OXA-23, OXA-51, BlaA2, Zn-dependent_hydrolase, ADC, Mbl and macrolide resistance genes MphE, MsrE were present in all 8 isolates. Conclusions: FOS-MEM and CL-MEM are promising combinations against A. baumannii. Synergy of FOS-MEM in intrinsically resistant A. baumannii shows that this antibiotic combination might be useful in treating such XDR and PDR pathogens. [ABSTRACT FROM AUTHOR]

Infections caused by multi-drug resistant Klebsiella pneumoniae are a leading cause of mortality and morbidity among hospitalized patients. In neonatal intensive care units (NICU), blood stream infections by K. pneumoniae are one of the most common nosocomial infections leading to poor clinical outcomes and prolonged hospital stays. Here, we describe an outbreak of multi-drug resistant K. pneumoniae among neonates admitted at the NICU of a large tertiary care hospital in India. The outbreak involved 5 out of 7 neonates admitted in the NICU. The antibiotic sensitivity profiles revealed that all K. pneumoniae isolates were multi-drug resistant including carbapenems and colistin. The isolates belonged to three different sequence types namely, ST-11, ST-16 and ST-101. The isolates harboured carbapenemase genes, mainly blaNDM-1, blaNDM-5 and blaOXA-232 besides extended-spectrum b-lactamases however the colistin resistance gene mcr-1, mcr-2 and mcr-3 could not be detected. Extensive environmental screening of the ward and healthcare personnel led to the isolation of K. pneumoniae ST101 from filtered incubator water, harboring blaNDM-5, blaOXA-232 and ESBL genes (blaCTX-M) but was negative for the mcr genes. Strict infection control measures were applied and the outbreak was contained. This study emphasizes that early detection of such high-risk clones of multi-drug resistant isolates, surveillance and proper infection control practices are crucial to prevent outbreaks and further spread into the community. [ABSTRACT FROM AUTHOR]

Purpose: To assess the fluoroquinolone resistance pattern and trends among bacterial isolates from ocular infections over a 16-year period and explore alternative antibiotics in fluoroquinolone-resistant strains.Methods: In this retrospective, longitudinal study, the microbiology laboratory records of patients with different ocular infections diagnosed at an eye institute in central India from 2005-2020 were reviewed to determine the pattern of fluoroquinolone (ciprofloxacin, ofloxacin, gatifloxacin, and moxifloxacin) resistance. Antibiotic susceptibility testing was done using the Kirby-Bauer disc diffusion method.Results: In 725 Gram-positive bacteria, the resistance of ciprofloxacin, ofloxacin, gatifloxacin, and moxifloxacin was 55.9% (95% confidence interval [CI]: 52.2 - 59.6), 42.7% (95% CI: 39.0 - 46.4), 47.6% (95% CI: 43.9 - 51.3), and 45.6% (95% CI: 41.7-49.5), respectively. In 266 Gram-negative bacteria, the resistance of ciprofloxacin, ofloxacin, gatifloxacin, and moxifloxacin was 57.9% (95% CI: 51.9 - 63.9), 56.0% (95% CI: 49.7 - 62.1), 59.9% (95% CI: 53.8 - 66.0), and 74.3% (95% CI: 68.3 - 80.2), respectively. A declining trend in resistance to ciprofloxacin (P < 0.001), ofloxacin (P < 0.001), and moxifloxacin (P < 0.001) was seen in Gram-positive bacteria, whereas a reduction in resistance to only moxifloxacin (P = 0.04) was seen in Gram-negative bacteria. In fluoroquinolone-resistant Gram-positive bacteria, cefuroxime exhibited the highest susceptibility, whereas in fluoroquinolone-resistant Gram-negative bacteria, colistin exhibited the highest susceptibility.Conclusion: Fluoroquinolone resistance was high among bacteria from ocular infections in central India, but a declining trend in resistance to some of the fluoroquinolones was observed in recent times. Cefuroxime and colistin emerged as alternatives in fluoroquinolone-resistant Gram-positive and Gram-negative bacterial infections, respectively. [ABSTRACT FROM AUTHOR]

Background: Indiscriminate use of colistin for gram-negative infections has led to increase incidence of colistin resistance. The problem of nosocomial infections especially caused by multi-drug-resistant gram-negative bacteria (MDR-GNB), particularly Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae is a matter of great concern. This study was conducted to find out the prevalence of colistin resistant gram-negative isolates from patients attending outdoor patient department (OPD), those admitted in wards and Intensive care unit from a Tertiary care centre in North-East India. Materials and Methods: Clinical samples obtained were processed using standard microbiological methods. The gram-negative isolates showing colistin resistance by Kirby-Bauer's disc diffusion method were included and further subjected for MIC (minimum inhibitory concentration) testing by VITEK-2 system followed by confirmation by Broth microdilution method. Results: Colistin resistance was observed in 26 isolates out of 1040 gram-negative isolates using Broth microdilution method. The MIC values varied from 8 to = 32 μg/ml. Majority of them belong to Pseudomonas species followed by Acinetobacter species and were highly resistant to ß-lactams, aminoglycosides, fluoroquinolones. Conclusion: This study highlights an increasing trend of colistin resistance amongst multidrug resistant (MDR) gram-negative isolates warranting routine screening for colistin resistance to guide appropriate therapy for future use. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the genomic differences between two extensively drug resistant, ST16 strains of Klebsiella pneumoniae recovered from patients in the same ICU, one of which was colistin resistant., Methods: Antimicrobial susceptibilities of the isolates were determined using VITEK-2. Hybrid assemblies for both strains were generated using Oxford Nanopore and Illumina technologies. The sequence type, capsule type, O-locus type, antimicrobial resistance determinants and plasmids carried by the isolates were inferred from the genome sequence. The phylogenetic placement, antimicrobial resistance, and virulence determinants of the isolates relative to a collection (n = 871) of ST16 isolates were assessed., Results: Both BC16, a colistin-resistant blood stream isolate and U23, a colistin-sensitive urinary isolate displayed near-identical antimicrobial resistance profiles and genome sequences with varying plasmid profiles. The BC16 genome only had 21 SNPs relative to U23 and belonged to the same capsule, O-antigen locus and multi-locus sequence types. The mgrB locus in BC16 was disrupted by an IS5 element. Phylogenetically, U23 and BC16 were placed on a clade with 4 strains belonging to K-type K48 and O-type O2a as opposed to majority (n = 807) of the strains (K-type K51 and O-type O3b)., Conclusions: BC16 was a colistin resistant derivative of U23, which evolved colistin resistance by an IS5-mediated disruption of the mgrB locus, likely during treatment of the index patient with colistin in the ICU. The strains belong to a rare subtype of ST16 with unique capsular and O-antigen types underscoring the utility of genomic surveillance networks and open-access genomic surveillance data in tracking problem clones., (Copyright © 2024. Published by Elsevier Ltd.)

For the first time, we describe the whole genome of a yellow-pigmented, capsuleproducing, pathogenic, and colistin-resistant Chryseobacterium gallinarum strain MGC42 isolated from a patient with urinary tract infection in India. VITEK 2 automated system initially identified this isolate as C. indologenes. However, 16S rRNA gene sequencing revealed that MGC42 shared 99.67% sequence identity with C. gallinarum-type strain DSM 27622. The draft genome of the strain MGC42 was 4,455,926 bp long with 37.08% Guanine-Cytosine (GC) content and was devoid of any plasmid. Antibiotic resistance, virulence, and toxin genes were predicted by implementing a machine learning classifier. Potential homologs of 340 virulence genes including hemolysin secretion protein D, metalloprotease, catalase peroxidases and autotransporter adhesins, type VI secretion system (T6SS) spike proteins, and 27 toxin factors including a novel toxin domain Ntox23 were identified in the genome. Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs of 110 transporter proteins were predicted that were in agreement with moderate efflux activity. Twelve antibiotic resistance genes including two potentially novel putative β-lactamase genes sharing low similarity with known β-lactamase genes were also identified in the genome of this strain. The strain MGC42 was also resistant to several classes of antibiotics along with carbapenems and polymyxin. We also identified mutations in the orthologs of pmrB (M384T) and lpxD (I66V) that might be responsible for colistin resistance. The MGC42 strain shared 683 core genes with other environmental and clinical strains of Chryseobacterium species. Our findings suggest that the strain MGC42 is a multidrug-resistant, virulent pathogen and recommend 16S rRNA gene sequencing to identify clinical specimens of Chryseobacterium species. [ABSTRACT FROM AUTHOR]

Enterobacterales particularly which are resistant to carbapenem group of antibiotics (CRE) are precariously being reported worldwide. Last option for treating the infections caused by CRE are polymyxin E (Colistin) and polymyxin B. Resistance to polymyxins is on higher side because of its increased usage both clinically and non-clinically. In vitro evaluation tests for susceptibility of colistin is associated with lot of complexities due to its innate cationic properties. Hence it is essential for all diagnostic laboratory to standardize colistin testing method, so the present study was undertaken to evaluate the results of colistin broth disk elution (CBDE) and colistin agar test (CAT) in comparison with the reference broth microdilution (rBMD). About 100 CRE clinical isolates were tested, results of CBDE & CAT was compared with rBMD. Categorical agreement (CA) of CBDE was 98% with 2% of very major error (VME), CA of CAT was 99% with 1% of VME in comparison with rBMD. Because of increasing colistin resistance it is crucial to report colistin MIC with a validated method, so we would like to recommend CAT test for routine MIC reporting of colistin since it is feasible test. [ABSTRACT FROM AUTHOR]

Objectives: Carbapenem-resistant organisms (CROs) are a significant public health threat globally, particularly in countries like India with high antibiotic resistance rates. The current study investigates the prevalence of CROs, detects resistance mechanisms using phenotypic methods and assesses the efficacy of newer antibiotics against CROs., Methods: A prospective study conducted at a tertiary care hospital in India during 2021-23. Clinical specimens were processed and bacterial identification was performed using MALDI-TOF mass spectrometry followed by antimicrobial susceptibility testing using CLSI guidelines against a plethora of newer antibiotics for CROs. Carbapenemase production was detected using phenotypic methods, and the presence of the mcr-1 gene was assessed by real-time PCR., Results: During the study period, predominantly (70 %) Gram-negative bacteria were isolated; amongst which 5692 strains were carbapenem-resistant, wherein resistance to different carbapenems ranged from 34.1% to 79 %. Majority of the carbapenemase producers were metallo-β-lactamases (MBL) producers (75 %). Colistin resistance was noted in 5.4 % of selected carbapenem-resistant isolates. Among newer antibiotics, cefiderocol demonstrated the lowest resistance rates (0-14 %), while resistance to newer β-lactam/β-lactamase inhibitor combinations was very high in carbapenem-resistant isolates. Fosfomycin, minocycline and tigecycline, each showing variable efficacy depending on the site of infection. Moreover, newer β-lactam/β-lactamase inhibitor combinations offer restricted benefits due to widespread prevalence of MBL in the region., Conclusion: The escalating prevalence of CROs in India underscores the urgency for alternative treatment options beyond colistin. Hence, highlighting the critical importance of developing effective strategies to combat carbapenem resistance., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Extensive drug resistance in Klebsiella pneumoniae (K. pneumoniae) causing major outbreaks in large hospitals is an emerging challenge. We describe a near fatal outbreak of colistin resistant, carbapenem resistant K. pneumoniae (CRKp) producing metallo beta-lactamases (blaNDM) and blaOXA-48 in the neonatal intensive care unit (NICU) at the background of a larger outbreak involving multiple parts of the hospital and the challenges in its containment. Methods: Following identification of an outbreak due to colistin resistant CRKp between April to June 2017 in the NICU, a thorough surveillance of similar cases and the hospital environment was performed to trace the source. All the isolated K. pneumoniae were tested for susceptibility to standard antibiotics by disc diffusion and microbroth dilution methods. Molecular detection of extended spectrum beta lactamases (ESBLs) and carbapenemases (classes A, B, D) genes was done. Enterobacterial repetitive intergenic consensus (ERIC) PCR and multi-locus sequence typing (MLST) was done to determine the genetic relatedness of the isolates. Characteristics of different sequence types were statistically compared (Student's t-test). Results: A total of 45 K. pneumoniae isolates were studied from NICU (14 cases of neonatal sepsis), ICU (18 cases), other wards (7 cases) along with 6 isolates from hospital environment and human colonizers. The primary case was identified in the ICU. All the K. pneumoniae from NICU and 94.4% from the ICU were colistin resistant CRKp. Majority (59.37% and 56.25%) harbored blaSHV/blaCTXM and blaOXA-48 genes, respectively. Two distinct sequence types ST5235 and ST5313 were noted with colistin resistance, distribution within the NICU and mortality as significant attributes of ST5235 (p < 0.05). The outbreak was contained with strengthening of the infection control practices and unintended short duration closure of the hospital. Conclusion: Large hospital outbreaks with considerable mortality can be caused by non-dominant clones of colistin resistant CRKp harboring blaOXA-48 and blaNDM carbapenemases in endemic regions. The exact global impact of these sequence types should be further studied to prevent future fatal outbreaks. [ABSTRACT FROM AUTHOR]

Aims: To generate preliminary data about comparative evaluation of two automated ID/AST systems and Mikrolatest kit in determining in vitro colistin susceptibility of carbapenem‑resistant Enterobacteriaceae spp. Materials and methods: Twenty‑three carbapenem‑resistant Escherichia coli and Klebsiella pneumoniae and two carbapenem‑sensitive multidrug‑resistant E. coli isolates obtained from various clinical samples of inpatients were included in the study. Species‑level identification and antibiotic susceptibility testing (AST) of test isolates was performed using BD phoenix and MicroScan WalkAway 96 Plus automated systems. Identity was reconfirmed by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI‑TOF MS). Additional colistin susceptibility testing was performed using Mikrolatest MIC colistin susceptibility testing kit (reference method). Results: Results showed that 16% isolates (27.3% [3/11] K. pneumoniae and 7.1% [1/14] E. coli) exhibited in vitro colistin resistance by the reference method. While the categorical agreement between BD Phoenix M50 ID/AST system and reference test w. r. t in vitro colistin susceptibility results was 100% and 92.9% for K. pneumoniae & E. coli, respectively, it was much lower between MicroScan WalkAway 96 plus ID/AST system and the latter. Almost perfect agreement (96%; kappa: 0.834) was observed between BD Phoenix M50 system and reference method. Conclusions: The results of this study are preliminary and cannot be generalized. Multicentric studies with large sample sizes should be conducted throughout the country to gain a deeper understanding of the subject under consideration. [ABSTRACT FROM AUTHOR]

This study describes comparative occurrence and characterization of multidrug-resistant (MDR) Escherichia coli and Klebsiella pneumoniae (KP) in healthy cattle (HC) and cattle with diarrhea (DC) in India. During 2018–2020, 72 MDR isolates, including 35 E. coli (DC: 27; HC 8) and 37 K. pneumoniae (DC: 34; HC: 3), from 251 rectal swabs (DC: 219; HC: 32) were investigated for extended-spectrum beta-lactamase (ESBL), AmpC type β-lactamase and carbapenemase production, antimicrobial susceptibility profile, biofilm production, and efflux pump activity. Fifty-five MDR isolates were ESBL producers (ESBLPs) (DC: 50; HC: 5) and ESBLPs from DC were coresistant to multiple antibiotics. The blaCTX-M gene (50) was the most frequently detected β-lactamases followed by blaAmpC (22), blaTEM1 (13), blaCMY-6 (6), blaOXA1 (5), blaPER (2), blaDHA, and blaFOX and blaSHV12 (1 each). Plasmid-mediated quinolone resistance determinants qnrB, qnrS, qnrA, and qepA were detected in 18, 16, 2, and 3 isolates, respectively. Twenty three isolates revealed mutation in gyrA and parC genes. Tetracycline-resistance markers tetA, tetB, tetC, and tetE were detected in 33, 10, 3, and 2 isolates, respectively. Only one of the 41 imipenem-resistant isolates harbored blaNDM-5 and two were colistin-resistant. Altogether, 20 MDR isolates were strong biofilm producers and 19 harbored different virulence factors. This is the first ever report from India on the presence of MDR Enterobacteriaceae with resistance to even last-resort antimicrobials in the bovine diarrhea. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) in poultry production chain is one of the major food safety concerns due to indiscriminate usage of antibiotics and the presence of pathogens such as Salmonella which causes infections in various stages of production. In the present study, 182 samples were collected from commercial broiler supply chain, viz., three hatcheries (n = 29), three commercial broiler farms (CBF; n = 99), and three retail meat shops (RMS; n = 54), and used for isolation and identification of Salmonella using three different selective agar media and a selective enrichment medium followed by PCR confirmation targeting the hilA gene. The overall prevalence of Salmonella was 47/182 (25.82%), and a significantly higher (P < 0.05) prevalence was observed in retail meat shops (46.29%), CBF (19.19%), and hatcheries (10.34%). Comparison of three agar media for isolation of Salmonella revealed that all the media were equally selective. However, PCR amplification of hilA gene fragment was significantly higher (P < 0.01) in selective enrichment culture tetrathionate brilliant green bile broth (TTB) as compared to all solid (agar-based) media. Susceptibility pattern against most frequently used antibiotics revealed that 100% of the isolates were resistant to at least one antibiotic. High resistance was observed for doxycycline (94.34%), followed by cefpodoxime (84.91%), ciprofloxacin (72.64%), gentamicin (65.09%), enrofloxacin (61.32%), colistin sulphate (40.42%), amikacin (34.91%), ampicillin (33.96%), neomycin (33.02), cefotaxime (30.19%), ceftazidime (29.25%), trimethoprim-sulfamethoxazole (23.58%), amoxicillin+clavulanic acid (21.70%), and chloramphenicol (12.26%); 16.98% of the isolates were ex-tended spectrum β-lactamase (ESBL) producers, and 76.41% were multidrug resistant (MDR). MDR Salmonella were significantly higher (P < 0.01) in RMS (91.66%) followed by CBF (82.75%), whereas no MDR isolates were present in the isolates from hatcheries. The results indicated a higher prevalence of Salmonella and AMR for commonly used antibiotics in the complete broiler supply chain, especially RMS and CBF. Also, this study idicated that TTB enrichment followed by PCR and colony PCR was found to be rapid, specific and time-saving method. [ABSTRACT FROM AUTHOR]

Background:Klebsiella pneumoniae (Kp), a common multidrug-resistant pathogen, causes a wide spectrum of nosocomial infections with high rates of morbidity and mortality. The emergence of pan drug-resistant international high-risk clones such as ST258, ST14, ST15, ST147, and ST101 is a global concern. This study was performed to investigate the carbapenemases, the plasmid profile, and the clonal relationship among Indian K. pneumoniae. Materials and Methods: A total of 290 K. pneumoniae isolates from seven centers in India were characterized to determine sequence types (STs) and carbapenemases. A subset of isolates was subjected to whole genome sequencing and hybrid genome assembly to obtain the complete genome. Plasmids carrying carbapenemases were characterized to determine the dissemination of carbapenem-resistant (CR) K. pneumoniae. Results: From this study, 75 different STs were observed with ST231 being predominant. About 79% of the analyzed isolates were CR with 59% (n = 136) producing OXA48-like carbapenemases. While ST231 was the predominant clone among the OXA48-like producers; NDM producers and NDM+OXA48-like producers were mostly associated with ST14. Interestingly, 61% (n = 138) of the total CR K. pneumoniae were colistin resistant, belonging to 22 different STs. Plasmid profiling shows that blaOXA48-like was exclusively carried by ColKP3, whereas blaNDM was associated with IncFII-like plasmids. Conclusion: The highly mosaic genome of K. pneumoniae coupled with the diverse ecological niches in India makes it a hotspot for antimicrobial resistance, leading to increased morbidity and mortality. Extensive molecular surveillance of the clonal spread of K. pneumoniae could help in understanding AMR dynamics and thus rework therapeutic management. [ABSTRACT FROM AUTHOR]

With virtually dried out new antibiotic discovery pipeline, emergence and spread of antimicrobial resistance is a cause for global concern. Colistin, a cyclic polypeptide antibiotic, often regarded as last resort for multi drug resistance gram-negative bacteria, is also rendered ineffective by horizontal transfer of resistance genes. Surveillance of colistin resistance in GNB is essential to ascertain molecular epidemiology. Whole genome sequencing (WGS) of an unusual colistin resistant urinary isolate of Escherichia coli was performed using Illumina MiSeq platform using 2x250bp V2 chemistry by following the manufactures protocol (Illumina Inc. USA). Multiple web-based bio-informatic tools were utilized to ascertain antibiotic resistant genes. An approximate 5.4 Mb of genome of the urinary isolate AFMC_UC19 was sequenced successfully. Mobile colistin resistance gene (mcr) on the plasmid responsible for horizontal spread was absent in the isolate. Colistin resistance has been reported previously in Klebsiella pneumoniae and it is a rare occurrence in Escherichia coli in Indian setting. Although the isolate lack mcr mediated colistin resistance, emergence and spread of colistin resistant in gram-negative bacteria pose a threat. [ABSTRACT FROM AUTHOR]

Multidrug-resistant Gram-negative bacterial infection is a serious global concern and especially in low and middle-income countries (LMIC) such as India. Colistin, an antimicrobial once abandoned following reports of organ toxicity, has re-emerged as an essential therapeutic agent in the management of these infections. A retrospective review of 162 inpatients was done, focusing on culture-proven multidrug-resistant infections requiring colistin. The overall clinical outcome in 58% of patients was found to be good, with nephrotoxicity and neurotoxicity occurring only in 8 (5%) and 4 (2.5%) patients, respectively. Multivariate analysis revealed an elevated lactate and raised urea to be independent factors associated with poor clinical response. In conclusion, there appears to be strong evidence supporting the use of colistin in the management of multidrug-resistant Gram-negative bacterial infections. [ABSTRACT FROM AUTHOR]

Background: Increasing use of colistin has led to the world-wide emergence of mobile colistin resistant gene (mcr). The present study aimed to identify and characterise mcr and other drug-resistant genes in colistin resistant Klebsiella pneumoniae clinical isolates. Methods: Twenty-two colistin resistant K. pneumoniae were analysed for mcr and other drug-resistant genes, efflux pumps, and virulence genes, and for their biofilm forming ability. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were performed for all mcr-1 positive isolates. S1-PFGE and Southern hybridisation were performed for localisation of mcr-1 and bla NDM. Results: Nineteen colistin resistant K. pneumoniae harboured mcr-1 and 3 had mgrB disruption. All isolates harboured bla OXA-48-type and ESBL genes; eight strains (five with mcr-1 and three with mgrB disruption) co-harboured bla NDM. Efflux pumps genes AcrAB and mdtK were detected in all 22 and tol-C in 21 isolates. Virulence-related genes entB and irp-1 were detected in all 22, mrkD in 20, and fimH-1 in 18 isolates; 11 isolates were strong biofilm producers. PFGE clustered mcr-1 positive isolates into eight groups based on ≥90% similarity; MLST revealed diverse sequence types, predominant being ST-15 (n = 4) and ST-16 (n = 4). Both mcr-1 and bla NDM were localised on plasmid and chromosome; mcr-1 was present on IncFII type and bla NDM on IncFIB and IncA/C type plasmids. Conclusions: Colistin resistance in K. pneumoniae was predominantly mediated by mcr-1. Co-existence of colistin, carbapenem, and other drug-resistant genes along with efflux pumps indicates towards enormous genomic plasticity in K. pneumoniae with ability to emerge as super-spreader of drug-resistance. [ABSTRACT FROM AUTHOR]

Background: Colistin resistance in Acinetobacter baumannii, the last resort drug for serious infections, is emerging worldwide. There has been paucity of data on this aspect from India, which is one of the largest producers of colistin. We studied colistin resistance in A. baumannii and characterized the isolates with respect to resistance mechanisms and virulence. Methods: A total of 365 A. baumannii isolates were studied. Antimicrobial susceptibility testing was performed as per standards. Colistin resistance mechanisms were studied by mutation detection in pmrA/B and lpxA/C/D genes, phenotypic loss of lipopolysaccharide, presence of mcr1–5 genes, and carbonyl cyanide 3-chlorophenylhydrazone (CCCP) effects. Biofilm formation, desiccation survival, and growth kinetics were studied and statistically analyzed for colistin-resistant and colistin-susceptible isolates. Results: All the colistin-resistant isolates (9, 2.5%) showed multiple mutations at novel sites in pmrA/B and/or lpxA/D genes with reversion of resistance with CCCP. Majority of these isolates (6, 66.6%) were from patients without prior colistin therapy. All received prior carbapenems. The resistant isolates demonstrated no significant difference in biofilm formation and desiccation survival but were slow growers. Conclusion: Mutations in pmrA/B and/or lpxA/D genes were the main resistance mechanism in these colistin-resistant isolates that showed no reduction in fitness. [ABSTRACT FROM AUTHOR]

Background: Ventilator-associated pneumonia (VAP) is an important cause of healthcare-associated infections, resulting in prolonged hospitalization with increased morbidity and mortality. Knowledge of predominant local pathogens and their antimicrobial susceptibility patterns helps in selection of appropriate initial antibiotic therapy in these critical cases. Aim and objective: The aim and objective of this study is to characterize the microbiology and antimicrobial susceptibility patterns of VAP isolates in a tertiary cancer center. Materials and methods: This is a 4-year qualitative observational study carried out at a tertiary care cancer hospital in Mumbai. All nondirect bronchoalveolar lavage specimens from patients with a clinical suspicion of VAP sent from the critical care unit to the department of microbiology were processed as per standard laboratory procedures. All isolates were identified to species level and an antimicrobial susceptibility testing was performed by the Kirby-Bauer disk diffusion method and/or the VITEK 2 automated identification and susceptibility system, according to Clinical and Laboratory Standards Institute guidelines. Results: The study comprised 1,074 patients: 710 (66.10%) men and 364 (33.90%) women. A total of 827 bacterial isolates were obtained with 780 (94.32%) gram-negative organisms and 47 (5.68%) gram-positive organisms; of which Acinetobacter baumannii (38.7%), Pseudomonas aeruginosa (17.5%), and Klebsiella pneumoniae (16.6%) were the commonest. Of gram-negative bacilli, multidrug-resistant organisms constituted 87.50% and were susceptible to colistin. Conclusions: VAP is associated with pathogens, such as A. baumannii, P. aeruginosa, and K. pneumoniae in our setting. High rates of resistance to aminoglycosides, β-lactam-β-lactamase inhibitor combinations, and carbapenems were noted. [ABSTRACT FROM AUTHOR]

Background: The resistance to colistin and carbapenems in Klebsiella pneumoniae infections have been associated with increased morbidity and mortality worldwide. A retrospective observational study was conducted to determine the prevalence and molecular events contributing to colistin resistance. Methods: Clinical samples were screened for colistin resistance and underlying mechanisms were studied by PCR-based amplification and sequence analysis of genes of two-component regulatory system (phoPQ and pmrAB), regulatory transmembrane protein-coding mgrB , and mobilized colistin resistance genes (mcr-1-8). Gene expression of pmrC and pmrK was analyzed by qRT-PCR, and the genetic relationship was assessed by MLST. The putative effect of amino-acid substitutions was predicted by a combination of bioinformatics tools. Results: Of 335 Klebsiella spp. screened, 11 (3.2%) were identified as colistin-resistant (MIC range, 8 to >128 μg/ml). K. pneumoniae isolates belonged to clonal complex-11 (CC11) with sequence types (STs): 14, 16, 43, 54, 147 and 395, whereby four isolates conferred three novel STs (3986, 3987 and 3988) profiles. Sequence analysis revealed non-synonymous potentially deleterious mutations in phoP (T151A), phoQ (del87–90, del263–264, L30Q, and A351D), pmrA (G53S), pmrB (D150V, T157P, L237R, G250C, A252G, R315P, and Q331H), and mgrB (C28G) genes. The mgrB gene in three strains was disrupted by insertion sequences encoding IS 1 -like and IS 5 /IS 1182 family-like transposase genes. All 11 isolates showed an elevation in the transcription level of pmrC gene. Mobilized colistin-resistance (mcr) genes were not detected. All but one of the colistin-resistant isolates was also resistant to carbapenems; β-lactamase genes blaNDM-1-like , blaOXA-48-like , and blaCTX-M-like were detected in eight, five, and nine isolates, respectively. Conclusion: All the studied colistin- and carbapenem-resistant K. pneumoniae isolates were genetically distinct, and various mechanisms of colistin resistance were detected, indicating its spontaneous emergence in this bacterial species. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance (AMR) is a global concern requiring immediate attention. Among many proven measures of decreasing AMR, practice of antimicrobial stewardship is the lowest hanging which can be adapted with negligible financial implications. Methods: This is a case record based extended cross-sectional type of observational operation research study conducted at an institute of national importance established by Government of India. Point prevalence of antibiotic usage among the patients admitted in the hospital, on four different days in four different quarters of a year was done to study the impact of antimicrobial stewardship program (AMSP). Results: A cumulative 711 patients were exposed on antibiotics among 1396 study participants. There was a significant decrease in antibiotic consumption across the 1st and 4th quarter. The average antibiotic usage was 50.9% (61.75, 60%, 48.4%, and 39% respectively in the 1st to 4th quarter). Among the total number of patients, intravenous antibiotic usage was 47.9% (60.71%, 58.4%, 44.9%, and 34.2% respectively in 1st to 4th quarter). Among the newly admitted patients, the consumption of antibiotic usage decreased from 45.9% to 25.7%. Among the intravenous antibiotics, the top 10 consumed antibiotics were 3rd generation cephalosporin (39.8%), aminoglycoside (14.8%), amoxicillin/amoxy-clav (12.5%), piperacillin-tazobactum (8.5%), carbapenams (6.6%), cefuroxime (6.4%), quinolones (4.3%), vancomycin/linezolid (4.1%), colistin (0.8%), and others (0.8%). Conclusion: Government run hospitals can run low budget antimicrobial stewardship program with sustainable impact on antibiotic consumption. For a successful AMSP, it requires change in attitude, commitment, and administrative support rather than a huge financial support. [ABSTRACT FROM AUTHOR]

Background: Colistin is a last-resort antibiotic used in extreme cases of multi-drug resistant (MDR) Gram-negative bacterial infections. Colistin resistance has increased in recent years and often goes undetected due to the inefficiency of predominantly used standard antibiotic susceptibility tests (AST). To address this challenge, we aimed to detect the prevalence of colistin resistance strains through both Vitek®2 and broth micro-dilution. We investigated 1748 blood, tracheal aspirate, and pleural fluid samples from the Intensive Care Unit (ICU), Neonatal Intensive Care Unit (NICU), and Tuberculosis and Respiratory Disease centre (TBRD) in an India hospital. Whole-genome sequencing (WGS) of extremely drug-resitant (XDR) and pan-drug resistant (PDR) strains revealed the resistance mechanisms through the Resistance Gene Identifier (RGI.v6.0.0) and Snippy.v4.6.0. Abricate.v1.0.1, PlasmidFinder.v2.1, MobileElementFinder.v1.0.3 etc. detected virulence factors, and mobile genetic elements associated to uncover the pathogenecity and the role of horizontal gene transfer (HGT)., Results: This study reveals compelling insights into colistin resistance among global high-risk clinical isolates: Klebsiella pneumoniae ST147 (16/20), Pseudomonas aeruginosa ST235 (3/20), and ST357 (1/20). Vitek®2 found 6 colistin-resistant strains (minimum inhibitory concentrations, MIC = 4 μg/mL), while broth microdilution identified 48 (MIC = 32-128 μg/mL), adhering to CLSI guidelines. Despite the absence of mobile colistin resistance (mcr) genes, mechanisms underlying colistin resistance included mgrB deletion, phosphoethanolamine transferases arnT, eptB, ompA, and mutations in pmrB (T246A, R256G) and eptA (V50L, A135P, I138V, C27F) in K. pneumoniae. P. aeruginosa harbored phosphoethanolamine transferases basS/pmrb, basR, arnA, cprR, cprS, alongside pmrB (G362S), and parS (H398R) mutations. Both strains carried diverse clinically relevant antimicrobial resistance genes (ARGs), including plasmid-mediated bla NDM-5 (K. pneumoniae ST147) and chromosomally mediated bla NDM-1 (P. aeruginosa ST357)., Conclusion: The global surge in MDR, XDR and PDR bacteria necessitates last-resort antibiotics such as colistin. However, escalating resistance, particularly to colistin, presents a critical challenge. Inefficient colistin resistance detection methods, including Vitek2, alongside limited surveillance resources, accentuate the need for improved strategies. Whole-genome sequencing revealed alarming colistin resistance among K. pneumoniae and P. aeruginosa in an Indian hospital. The identification of XDR and PDR strains underscores urgency for enhanced surveillance and infection control. SNP analysis elucidated resistance mechanisms, highlighting the complexity of combatting resistance., (© 2024. The Author(s).)

Introduction: The emergence of resistance to colistin urges the need for standardised invitro susceptibility testing methods for colistin, both for patient care and also for epidemiological purpose. Many challenges have been faced by clinical laboratories in performing and interpreting Antimicrobial Susceptibility Testing (AST) methods for colistin. To overcome the challenges, a rapid and reliable method is required to carry out AST for colistin. Aim: To determine the degree of agreement and types of errors associated with various colistin antimicrobial susceptibility methods such as commercial Broth Microdilution (BMD) method (MIKROLATEST- Erba Mannheim colistin MIC kit) and in-house Rapid polymyxin NP test (named after P. Nordmann and L. Poirel) with the reference in-house BMD method. Materials and Methods: The study was carried out in a tertiary care hospital in southern India from July 2018 to July 2019. The isolates from Enterobacteriaceae family showing resistance to carbapenem were selected for the study. A total of 294 clinical isolates were collected and subjected to two test methods (Commercial BMD method and Rapid polymyxin NP test) and finally the comparative analytical study was done by comparing the results of the test methods with reference in-house BMD method. The statistical analysis was carried out with the help of Stata version 14 using kappa statistics. Results: Susceptibility results of 294 isolates included Escherichia coli (n=67), K.pneumoniae (n=195), Enterobacter spp. (n=23), Citrobacter spp. (n=9) were evaluated for three methods according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) published clinical breakpoints. Overall, categorical agreement of commercial BMD with reference in-house method was 91.1% with very major error 2.7% and major error 6.1% and essential agreement was 83.3%. With the Rapid polymyxin NP test, categorical agreement, sensitivity and specificity were 92.5%, 93.1% and 92.3% respectively. Conclusion: This study helps in introducing less laborious, faster and reliable susceptibility method for colistin. This will guide the clinicians in appropriate and judicious use of colistin so that mortality and morbidity will be reduced drastically. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a serious global threat driven by the overuse of drugs in humans, animals, as well as the contamination of natural environments with antimicrobial residues. In recent years, the rise of community-acquired infections resistant to antibiotics has drawn renewed attention to the environmental compartment, in particular for pathogens found in aquaculture systems. We quantified the prevalence of antibiotic resistance in Vibrios isolated from the Cochin Estuary as well as the adjoining shrimp farms, and seafood from markets. A total of 280 Vibrio strains were subjected to antimicrobial susceptibility testing and screened for the presence of blaTEM, blaCTX-M, and blaNDM-1 genes. All strains identified were resistant to at least three antimicrobials, and the percentage of drugs resistant per strain ranged from 16% up to 60%. All the strains from the estuary were resistant to amoxicillin, ampicillin, cephalothin, and colistin. Similarly, strains isolated from seafood were resistant to enrofloxacin, furazolidone, and trimethoprim, and all strains from shrimp farms were resistant to colistin. Plasmid-mediated antibiotic resistance was observed in 21% of the strains. In addition, the presence of blaNDM-1 gene was confirmed in 22.85% of the strains. The presence of multiple resistant phenotypes in vibrios, including resistance to last-resort compounds in domestic food sources, raises serious concerns for public health in the Cochin Estuary. Although localized in nature, our findings also have vital implications for the spread of AMR internationally, given the prominence of South India for seafood exports. [ABSTRACT FROM AUTHOR]

In this study, we investigated the prevalence of ESBLs producing bacteria from highly polluted stretch of river Yamuna and co-occurrence of ESBLs and silver resistance gene among tested isolates. Water samples were collected from ten different polluted sites from Delhi stretch of river Yamuna, India. Out of 399 non-duplicate isolates screened, 121 (~ 30%) were found to be ESBLs producers. ESBLs positive isolates showed high level of resistance for β-lactam and non-β-lactam antibiotics, viz. ampicillin, cephalosporins, ciprofloxacin and polymyxin-B. A significantly high level of resistance (26.4%) was observed for last resort antibiotic colistin. 69% of ESBLs positive isolates exhibited multidrug resistance phenotype and high MAR index of different sampling sites ranging from 0.21 to 0.68. Molecular characterization revealed that blaCTX-M was the most prevalent type of ESBL (60.3%) followed by blaTEM (47.9%) and blaSHV (15.7%). We further observed co-occurrence of silver resistance determinants silE, silP and silS in 49.3%, 53.4% and 36.9% isolates harboring blaCTX-M genes. Conjugation transfer assay confirmed the successful transfer of plasmid encoding ESBLs and silver resistance determinants together. To the best of our knowledge, this is first report of co-occurrence of CTX-M and silver resistance gene from aquatic environment. Moreover, this study reports occurrence of ESBL genes in Bacillus safensis and Brachymonas chironomi not reported earlier. Co-occurrence of sil and blaCTX-M gene strengthens the hypothesis of heavy metal exert selection pressure for the emergence of antibiotic resistance. [ABSTRACT FROM AUTHOR]

The word antibiotic means "against life." It highlighted upon the ban of antibiotics for growth promotion, particularly those which were meant for human therapy.[[3]] However, usage of antibiotics such as avoparcin, bacitracin, virginiamycin, bambermycin, and tylosin continued as narrow-spectrum substitutes which had less impact on the wide range of gut flora. E. coli and K. pneumoniae exhibited very high resistance to antibiotics such as penicillins, fluoroquinolones, and third- and fourth-generation cephalosporins and carbapenems, which are the last resort antibiotics in hospitals. They claimed to advertise that "antibiotics will make the animals grow bigger and faster", thus supplying the antibiotics to Indian farmers, and also reported that antibiotics, when used properly for approved indications and under the supervision of a veterinarian, do not pose a threat to public health. [Extracted from the article]

Aim:Klebsiella pneumoniae carbapenemase (KPC) is a class A carbapenemase endemic in the United States, China, South America, and Europe but is rarely reported from India. A single report of KPC-9 from K. pneumoniae in Israel has been published. K. pneumoniae has been classified into three phylogenetic groups: group 1 consists of K. pneumoniae and its subspecies, group 2 consists of Klebsiella quasipneumoniae and its subspecies, and group 3 consists of Klebsiella variicola. This is the first report of whole-genome sequencing of colistin-resistant K. quasipneumoniae subsp. similipneumoniae harboring blaKPC-9 gene. Results: The isolate was obtained from the culture of a respiratory catheter tip from a 41-year-old woman with traumatic brain injury. Whole-genome sequencing showed the presence of blaOKP-B-3 gene and hence it was identified as K. quasipneumoniae subsp. similipneumoniae. The isolate was resistant to all antimicrobials except tigecycline. Colistin resistance was chromosomally mediated; mcr-1 to mcr-5 genes and their variants were not identified. The isolate belonged to the novel clonal type ST2957. Conclusion: The isolation of KPC-9 from India, a nonendemic region, and in an isolate of K. quasipneumoniae highlights the importance of accurate identification of Klebsiella species and determination of mechanism of resistance. The novel sequence type obtained indicates evolution of the organism and acquisition of plasmid-mediated resistance. The occurrence of KPC in India is a potential public health threat. [ABSTRACT FROM AUTHOR]

Background & objectives: Klebsiella pneumoniae (KP), a common cause of invasive infections, is often extensively drug resistant in India. At present, studies on resistance mechanism and clonal relationship of KP from India are limited. The present study was undertaken to determine the resistance mechanism and clonal relationship of colistin-resistant isolates obtained from various specimens. Carbapenemases were also determined since the isolates were carbapenem resistant. Methods: Sixty five isolates from blood, exudates and respiratory specimens collected between 2016 and 2017 were studied. Colistin minimum inhibitory concentration (MIC) was performed by broth-micro dilution method. Multiplex PCR was carried out to determine carbapenemases. Targeted sequencing was performed to determine mutations in mgrB, phoP, phoQ and multilocus sequence typing was performed to determine the prevalent clones. Results: Colistin MIC ranged from 4 to 256 μg/ml. SHV, TEM and CTX-M were co-produced in 60 per cent and OXA48-like in 71 per cent. Thirteen isolates had mutations in mgrB. Mutations included a premature stop codon at 21st amino acid, the presence of insertion sequences such as IS903, IS Kpn 14 and ISK pn 26; and elongation of mgrB. Novel mutations were also observed among phoP and phoQ genes. Colistin resistance due to mcr genes was absent. Fifteen clonal types were seen with ST231, ST14 and ST2096 being predominant. Interpretation & conclusions: This study revealed the changing trend of carbapenem resistance mechanism predominantly to OXA48-like from NDM. Known mgrB mutations and novel mutations in phoP and phoQ were detected. There was no plasmid-mediated colistin resistance. ST14 and ST231 were international clones associated with carbapenem resistance. Colistin-resistant KP was of diverse clones with predominantly ST231, ST14 and ST2096. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine the optimal dosage of colistin according to colistin concentrations and the creatinine clearance rate (CLCR) in 21 critically ill haemodialysis and non-haemodialysis patients with Gram-negative bacterial infections admitted to a tertiary care hospital in India.Methodology and design: Blood samples were collected from patients after the fourth dose of colistin to measure the trough concentrations of colistin using high-pressure liquid chromatography. Additionally, CLCR was calculated using the Cockcroft-Gault equation, and serum creatinine values were used to assess nephrotoxicity.Results: The optimum therapeutic range of colistin in plasma was considered to be 5-17 µg/ml. Three haemodialysis patients had high plasma colistin concentrations of 25.27 ± 6.65 µg/ml and three non-haemodialysis patients had high colistin concentrations of 36.56 ± 17.26 µg/ml. Six patients had a CLCR value < 20 ml/min. The dosage of colistin in patients with high colistin plasma concentrations and low CLCR was reviewed.Conclusion: For this group of patients, based on trough concentrations of colistin, CLCR, and clinician’s clinical experience, a reduction of colistin dosage in haemodialysis patients and non-haemodialysis patients, respectively, was suggested to lower elevated plasma colistin concentrations. This dosage reduction may reduce the signs associated with nephrotoxicity and promote improvements in patient life and colistin-related outcomes. [ABSTRACT FROM AUTHOR]

Background: Chryseobacterium indologenes is a hospital environment contaminant and can cause healthcare-associated infections. Methods: Patients with C. indologenes infections in a tertiary care center in North India for 6 months were evaluated for susceptibility patterns, comorbidities, mechanical devices, risk factors, and treatment outcomes. The organism was provisionally identified phenotypically, and identification was confirmed by the BD Phoenix automated microbiology system. Minimum inhibitory concentration values of antibiotic susceptibility were determined. Results: A total of 12 isolates of C. indologenes were recovered from 11 patients. Five patients had C. indologenes bloodstream infection (BSI), one had ventilator-associated pneumonia (VAP), and one had both BSI and VAP. In four others, the organism was isolated from the catheterized urinary tract. All VAP and BSI patients were admitted to the Intensive Care Units and mechanically ventilated; all had central lines and history of colistin therapy during the past 15 days. The common underlying risk factors were diabetes, hypertension, and coronary artery disease. Conclusions: C. indologenes infections are increasing because of higher use of carbapenems and colistin, to which it is intrinsically resistant. [ABSTRACT FROM AUTHOR]

Background: Antibiotic resistance is a serious problem being faced by physicians worldwide. This article was designed to study physician perceptions of antibiotic resistance and their prescribing patterns. Materials and Methods: A structured questionnaire was developed for reporting the prevalence of antibiotic resistance as perceived by physicians and recording their antibiotic preferences in specific contexts. A total of 539 intensivists across India participated in the study. Results: The prevalence of multidrug-resistant (MDR) Gram-negative pathogens was reported to be on the rise in Intensive Care Units. The prevalence rate of carbapenem-resistant Enterobacteriaceae was reported to be between 20% and 40% by 33% of the participants. Piperacillin-tazobactam was the preferred beta-lactam/beta-lactamase inhibitor antibiotic by the majority of intensivists (47%) in the treatment of infections caused by extended-spectrum beta-lactamase producers. Meropenem was recommended to be used at a higher dose (2 g t.i.d.) by 41% of intensivists for Pseudomonas/Acinetobacter infections with high minimum inhibitory concentration values for meropenem. De-escalation data revealed that 43% of intensivists "always" would like to de-escalate from carbapenems, based on the antibiotic susceptibility data. Minocycline was recommended by 33% for the treatment of ventilator-associated pneumonia (VAP) and by 21% for bloodstream infections caused by MDR Acinetobacter. Up to 83% of intensivists preferred the use of nebulized colistin for the management of VAP/hospital-acquired pneumonia. Conclusion: This study reveals that the prevalence of MDR Gram-negative pathogens is perceived to be on the rise. Prescription patterns indicate high levels of variability. Hence, antibiotic stewardship is essential to standardize antibiotic prescriptions not only for efficacy but also to reduce the burden of multiple drug resistance. [ABSTRACT FROM AUTHOR]

Introduction: Ventilator-associated pneumonia (VAP) is one of the most common infections in mechanically ventilated patients. VAP is usually caused by multidrug resistant bacteria. The beta-lactam antibiotics, which were once considered the backbone of antibiotic therapy is under strain due to a variety of bacterial antibiotic resistance. Recent evidence suggests that colistin is the only cannon left in the medical armory to treat bacterial infections, mainly those acquired in the hospital that no other drug can treat. But excessive use of colistin has recently led to resistance to these group of drugs. Initially, resistance to colistin was due to mutations but recently detected plasmid-mediated colistin resistance, which is transferrable, heralds the breach of the last group of antibiotics, polymixins. Colistin resistance is on the rise, especially in South East Asia countries. So strict infection control policies are required to control the spread of this infection. Objective: This study was conducted to see the burden of colistin resistant organisms causing VAP in ICU of Himalayan Institute of Medical Sciences, Dehradun, India. Design: A prospective observational study. Setting: Study was conducted in a 40-bed semi-closed ICU of a tertiary care super specialized hospital between August 2016 to April 2017. Patients and participants: Out of 2304 patients admitted to ICU 420 had a suspicion of VAP. A total of 476 lower respiratory tract samples were collected from 400 patients with clinical evidence of lower respiratory tract infections in form of endotracheal (ET) aspirate, tracheal tube (TT) aspirate, and bronchoalveolar lavage (BAL) specimens. Intervention: Organism identification and the susceptibility testing were done by using an automated system VITEK 2. Result: Out of 476 sample received, only 186 samples organisms were isolated, which showed Acinetobacter baumanii was the most common organism. It was found that 19 organisms had resistance to colistin. Klebsiella pneumoniae (25.7%) was the most common organism, which was resistant to colistin, followed by Pseudomonas aeruginosa (16%) and Acinetobacter baumanii (2.4%). Conclusion: The emergence of colistin resistant strains is a very serious problem as there are only few treatment options. As colistin use is a risk factor for colistin resistance, colistin should not be used alone, combination therapy should be preferred. [ABSTRACT FROM AUTHOR]

Introduction: There have been isolated case reports and reports of outbreak of colistin-resistant Klebsiella from various parts of the world but only two from India and that too from oncology centers. We report cluster of colistin-resistant Klebsiella pneumonia bloodstream infection cases from our surgical trauma Intensive Care Unit. Methodology: The study was carried out in surgical ICU of Level-I trauma center. Retrospective analysis of all the five patients with CRK was done. Demographic data, antibiotic exposure throughout the hospital stay, hospital course, and clinical outcome were analyzed. Results: Out of 5 patients, 4 were young males (mean age of 23.5 years) without comorbidities and had undergone exploratory laparotomy following blunt trauma abdomen. 3 patients were chronic patients and had been on carbapenem and colistin 11-20 days before isolation whereas 2 patienst had isolation of CRK just within 7 days of admission. Out of the five patients, 3 patients survived and 2 had fatal outcome. Conclusions: CRK is an emerging and challenging pathogen in polytrauma victims . There was an outbreak of CRK in our ICU that could be contained with infection control measures. [ABSTRACT FROM AUTHOR]

Background: Superiority of colistin--carbapenem combination therapy (CCCT) over colistin monotherapy (CMT) against carbapenem-resistant Gram-negative bacterial (CRGNB) infections is not conclusively proven. Aim: The aim of the current study was to analyze the effectiveness of both strategies against CRGNB nonbacteremic infections. Design: This was a retrospective observational cohort study. Subjects and Methods: Case record analysis of patients who had CRGNB nonbacteremic infections identified over a period of 4 years (January 2012-December 2015) was done by medical record review at a tertiary care center in India. Statistical Analysis: P < 0.05 was considered as significant. Multivariate analysis was performed using Cox regression. Results: Out of 153 patients (pneumonia 115, urinary tract infection 17, complicated skin and soft-tissue infection 18, intra-abdominal infection 1, and meningitis 2), 92 patients received CCCT and 61 received CMT. Univariate analysis revealed higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score, pneumonia as the diagnosis, and Klebsiella as the causative organism to be the risk factors for higher 28-day mortality (P = 0.036, 0.006, 0.016, respectively). Combination therapy had no significant impact on mortality (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.327-2.535, P = 0.857). Multivariate analysis revealed that higher APACHE II score and infection due to Klebsiella were found to be independent risk factors for higher mortality (OR = 3.16 and 4.9, 95% CI = 1.34-7.4 and 2.19-11.2, P = 0.008 and 0.0001, respectively). Conclusions: In our retrospective single-center series of CRGNB nonbacteremic infections, CCCT was not superior to CMT. Multicenter large observational studies or prospective randomized clinical trials are the need of the hour. [ABSTRACT FROM AUTHOR]

Context: Limited Indian data are available on the rate of colistin nephrotoxicity and other risk factors contributing to the development of this important side effect. Aim: This study aims to generate data on colistin nephrotoxicity from a large cohort of Indian patients. Design: Retrospective cohort study. Materials and Methods: Case record analysis of patients who received colistin, in an oncology center in India, between January 2011 and December 2015. Nephrotoxicity was assessed using risk, injury, failure, loss, and end-stage (RIFLE) criteria. Statistical Analysis: P < 0.05 was considered as statistically significant. Results: Out of the 229 patients, 13.1% (30/229) developed abnormal RIFLE. Abnormal RIFLE group (n = 30), in comparison to the normal renal function group (n = 199), had higher number of patients in intensive care unit (ICU) (96% vs. 79%, P = 0.02), higher Acute Physiology and Chronic Health Evaluation (APACHE II) score (23 vs. 19 P = 0.0001), Charlson score (5.9 vs. 4.3, P = 0.001), mechanical ventilation (90% vs. 67%, P = 0.016), 28 days mortality (63% vs. 25%, P = 0.0001), and abnormal baseline creatinine (36% vs. 8%, P = 0.001). Coadministration of vancomycin had higher rates of nephrotoxicity (P = 0.039). There was no significant difference in nephrotoxicity between 6 and 9 MU/day dosing pattern (8.8% vs. 13.8%, P = 0.058). Conclusion: Nephrotoxicity rate in our retrospective single center large series of patients receiving colistin was 13.1%. Patients with abnormal baseline creatinine, ICU stay, and higher disease severity are at higher risk of nephrotoxicity while on colistin. A daily dose of 9 million does not significantly increase nephrotoxicity compared to the 6 million. Concomitant administration of vancomycin with colistin increases the risk of nephrotoxicity. [ABSTRACT FROM AUTHOR]

Background: As the use of colistin to treat carbapenem-resistant Gram-negative infections increases, colistin resistance is being increasingly reported in Indian hospitals. Materials and Methods: Retrospective chart review of clinical data from patients with colistin-resistant isolates (minimum inhibitory concentration >2 mcg/ml). Clinical profile, outcome, and antibiotics that were used for treatment were analyzed. Results: Twenty-four colistin-resistant isolates were reported over 18 months (January 2014-June 2015). A history of previous hospitalization within 3 months was present in all the patients. An invasive device was used in 22 (91.67%) patients. Urine was the most common source of the isolate, followed by blood and respiratory samples. Klebsiella pneumoniae constituted 87.5% of all isolates. Sixteen (66.6%) were considered to have true infection, whereas eight (33.3%) were considered to represent colonization. Susceptibility of these isolates to other drugs tested was tigecycline in 75%, chloramphenicol 62.5%, amikacin 29.17%, co-trimoxazole 12.5%, and fosfomycin (sensitive in all 4 isolates tested). Antibiotics that were used for treatment were combinations among the following antimicrobials-tigecycline, chloramphenicol, fosfomycin, amikacin, ciprofloxacin, co-trimoxazole, and sulbactam. Among eight patients who were considered to have colonization, there were no deaths. Bacteremic patients had a significantly higher risk of death compared to all nonbacteremic patients (P = 0.014). Conclusions: Colistin resistance among Gram-negative bacteria, especially K. pneumoniae, is emerging in Indian hospitals. At least one-third of isolates represented colonization only rather than true infection and did not require treatment. Among patients with true infection, only 25% had a satisfactory outcome and survived to discharge. Fosfomycin, tigecycline, and chloramphenicol may be options for combination therapy. [ABSTRACT FROM AUTHOR]

Increased use of colistin, a last resort drug due to failure of carbapenems, has possibly contributed in development and spread of resistance to colistin among Enterobacteriaceae. The colistin belongs to the family of polymyxins, cationic polypeptides, with broad-spectrum activity against Gram-negative bacteria. In this study, we obtained 253 non-duplicate bacterial isolates from sewage water in Delhi and phenotypically screened for colistin resistance. Of the 47 positive isolates, the colistin resistance gene mcr-1 was detected among 5 isolates. Based on 16S ribosomal RNA–based identification, bacterial isolates were found to be Escherichia coli, Aeromonas veronii, and Aeromonas dhakensis. Extended spectrum β-lactamases (ESBL)–resistant determinants CTX-M and TEM were detected in all five mcr-1 positive isolates. On the basis of literature survey, this is the first report of mcr-1 gene from Aeromonas veronii and Aeromonas dhakensis worldwide. Furthermore, mcr-1 gene has not been reported earlier from sewage water in India. Antibiotic susceptibility test of all five isolates against 9 different classes of drugs revealed multidrug-resistant phenotype with high minimum inhibitory concentration values. In vitro transconjugation studies showed successful transfer of mcr-1 and other ESBL-resistant determinants. The occurrence of colistin resistance phenotype conferred by plasmid-based mcr-1 gene in the environment and an ever-increasing list of bacterial isolates is a cause of concern. A comprehensive survey of different water bodies and epidemiological studies are required to assess the risk of dissemination of resistance determinants. [ABSTRACT FROM AUTHOR]

Infections caused by multi-drug resistant Klebsiella pneumoniae are a leading cause of mortality and morbidity among hospitalized patients. In neonatal intensive care units (NICU), blood stream infections by K. pneumoniae are one of the most common nosocomial infections leading to poor clinical outcomes and prolonged hospital stays. Here, we describe an outbreak of multi-drug resistant K. pneumoniae among neonates admitted at the NICU of a large tertiary care hospital in India. The outbreak involved 5 out of 7 neonates admitted in the NICU. The antibiotic sensitivity profiles revealed that all K. pneumoniae isolates were multi-drug resistant including carbapenems and colistin. The isolates belonged to three different sequence types namely, ST-11, ST-16 and ST-101. The isolates harboured carbapenemase genes, mainly bla NDM-1 , bla besides extended-spectrum β-lactamases however the colistin resistance gene NDM-5 and bla OXA-232 besides extended-spectrum β-lactamases however the colistin resistance gene mcr-1 , mcr-2 and mcr-3 could not be detected. Extensive environmental screening of the ward and healthcare personnel led to the isolation of K. pneumoniae ST101 from filtered incubator water, harboring bla NDM-5 , bla OXA-232 and ESBL genes ( bla CTX-M ) but was negative for the mcr genes. Strict infection control measures were applied and the outbreak was contained. This study emphasizes that early detection of such high-risk clones of multi-drug resistant isolates, surveillance and proper infection control practices are crucial to prevent outbreaks and further spread into the community., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pathak, Tejan, Dubey, Chauhan, Fatima, Jyoti, Singh, Bhayana and Sahu.)

Plasmid mediated colistin resistance was absent; mutations in mgrB, phoP and phoQ were predominant cause of colistin resistance. Susceptible ST23 hvKp carried only the virulence plasmid while MDR ST23 isolates carried 6 plasmids with resistance genes apart from virulence plasmid. B Background: b Klebsiella pneumoniae (Kp) is a notorious pathogen with high rates of extensively drug resistant isolates across the globe. [Extracted from the article]

Purpose: Colistin, which had not been used widely because of nephrotoxicity and neurotoxicity, has gained clinical importance in recent times due to the resurgence of multidrug-resistant Gram-negative bacilli. Very few studies, especially pharmacokinetic studies, have been performed with intravenous colistimethate sodium, and none in India. The aim of our study was to study the single-dose and steady-state pharmacokinetics of colistin in patients with multidrug-resistant Gram-negative bacilli infections. Method: This was a prospective open-label pharmacokinetic study done in an intensive care unit in a tertiary care hospital on 15 critically ill patients with proven multidrug-resistant Gram-negative bacilli infection. Colistimethate sodium was injected as intermittent intravenous infusions in accordance with the recommendations on the package insert. For patients weighing ≥60 kg with a normal renal function or with a creatinine clearance (CL) of between 20 and 50 ml/min, the drug was administered at 2 million international units (MIU) every 8 h; for those with a CL of 10-20 ml/min, the dose was 2 MIU every 12 h. Those patients who weighed <60 kg were administered 50,000 IU/kg/day in three divided doses at 8-h intervals. Both single-dose and steady-state pharmacokinetics of colistin were determined and correlated with clinical outcomes. Results: A wide inter-individual variation was observed in pharmacokinetic parameters. The median (range) of the maximum plasma drug concentration/minimum inhibitory concentration (C/MIC) ratio for Acinetobacter spp. was 13.4 (1.3-40.3) following the administration of a single dose of colistimethate sodium and 26.3 (0.9-64.9) at steady-state. For Pseudomonas spp., these values were 3.18 (1.6-23.1) following the single dose and 3.82 (2.3-10.9) at steady-state. For those patients whose cultures grew Acinetobacter spp., an optimum value of the C/MIC ratio of >8 was achieved in seven of nine patients after the single dose and in seven of eight patients at steady-state. For those patients whose cultures grew Pseudomonas spp, only one patient after the single dose and one patient at steady-state achieved a C/MIC ratio of >8. A significant association was noted between dose and survival, and a trend was observed with patients weighing ≤60 kg (who received 50,000 IU/kg/day instead of 6 MIU/day for those >60 kg) having an increased mortality. Conclusion: The pharmacokinetic parameters of colistin were comparable to those reported in previous studies in critically ill patients. However, the recommended dose may be inadequate to maintain the C/MIC ratio to an optimal level-at least in patients infected with Pseudomonas spp. The dose recommendation should be based only on creatinine clearance and not body weight. [ABSTRACT FROM AUTHOR]