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Introduction: International guidelines recommend definitive combination antibiotic therapy for the management of serious infections involving carbapenem-resistant Acinetobacter(CRAB) species. The commonly available combination options include high-dose sulbactam, polymyxins, tetracyclines, and cefiderocol. Scanty prospective data exist to support this approach. Methods: Patients with CRAB bacteraemia, ventilator-associated pneumonia (VAP), or both were categorized based on whether they received combination therapy or monotherapy. The 30-day mortality was compared between the two groups. Inverse probability treatment weighting (IPTW) was done using propensity score (PS) for a balanced comparison between groups. Results: Between January 2021 and May 2023, of the 161 patients with CRAB bacteraemia (n= 55, 34.2%), VAP (n= 46, 28.6%), or both (n= 60, 37.3%) who received appropriate intravenous antibiotic therapy, 70% (112/161) received monotherapy, and the rest received combination therapy. The overall 30-day mortality was 62% (99/161) and not different (p= 0.76) between the combination therapy (31/49, 63.3%) and monotherapy (68/112, 60.7%) groups. The propensity score matching using IPTW did not show a statistical difference (p= 0.47) in 30-day mortality for receiving combination therapy with an adjusted odds ratio (OR) Pof 1.29 (0.64, 2.58). Conclusion: Combination therapy for CRAB infections needs further study in a randomised controlled trial, as this observational study showed no difference in 30-day mortality between monotherapy and combination therapy.

AbstractIn an Indian oncology setting, between August and December 2021, 56 patients, developed Burkholderia cenocepaciabacteremia. An investigation revealed a contaminated batch of the antiemetic drug palonosetron. The outbreak was terminated by withdrawing the culprit batch and the findings were reported promptly to regulatory authorities.

Introduction: The objective of this study was to examine the evolution of carbapenem-resistant Klebsiella pneumoniae(CRKp) infections and their impact at a tertiary care hospital in South India. Methods: A comparative analysis of clinical data from two prospective cohorts of patients with CRKp bacteremia (C1, 2014–2015; C2, 2021–2022) was carried out. Antimicrobial susceptibilities and whole genome sequencing (WGS) data of selected isolates were also analyzed. Results: A total of 181 patients were enrolled in the study, 56 from C1 and 125 from C2. CRKp bacteremia shifted from critically ill patients with neutropenia to others (ICU stay: C1, 73%; C2, 54%; p= 0.02). The overall mortality rate was 50% and the introduction of ceftazidime-avibactam did not change mortality significantly (54% versus 48%; p= 0.49). Oxacillinases (OXA) 232 and 181 were the most common mechanisms of resistance. WGS showed the introduction of New Delhi metallo-β-lactamase-5 (NDM-5), higher genetic diversity, accessory genome content, and plasmid burden, as well as increased convergence of hypervirulence and carbapenem resistance in C2. Conclusions: CRKp continues to pose a significant clinical threat, despite the introduction of new antibiotics. The study highlights the evolution of resistance and virulence in this pathogen and the impact on patient outcomes in South India, providing valuable information for clinicians and researchers.

The COVID-19 pandemic was unique in the history of outbreaks because of the massive scaling up of resources related to diagnostics, treatment modalities, and vaccines. To understand the impact of the pandemic among laboratory professionals, we aimed to conduct a survey to assess the improvement in the lab capacity post-covid in terms of infrastructure and accreditation status across various levels of hospitals and to determine the changes in the practice of infection control precautions during the pandemic.

Bacteria acquire β-lactam resistance through a multitude of mechanisms among which production of β-lactamases (enzymes that hydrolyze β-lactams) is the most common, especially in Gram-negatives. Structural changes in the high-molecular-weight, essential penicillin-binding proteins (PBPs) are widespread in Gram-positives and increasingly reported in Gram-negatives. PBP-mediated resistance is largely achieved by accumulation of mutation(s) resulting in reduced binding affinities of β-lactams. Herein, we discuss PBP-mediated resistance among ESKAPE pathogens that cause diverse hospital- and community-acquired infections globally.

Biapenem has been recently approved by the Drug Controller General of India for the treatment of complicated urinary tract infections (cUTI). However, there are no assessment studies that evaluate the in-vitroactivity of biapenem against contemporary ESBL-producing Indian Enterobacterales isolates. To determine the activity of biapenem against contemporary ESBLs and/or OXA-1/ampC producing Enterobacterales and Pseudomonas aeruginosaisolates.

Invasive non-typhoidal Salmonella(iNTS) disease is an important cause of morbidity and mortality in African countries. However, the incidence in Indian subcontinent remains poorly documented. This study has assessed the incidence of iNTS in India with a perspective on its AMR profiles and serovar distribution for a period of 21 years from 2000 to 2020 from a tertiary care centre in South India.

An emerging pathotype of Klebsiella pneumoniae, initially identified in Southeast Asian countries, has now spread to multiple countries, including India. These convergent strains, carrying both resistance and virulence determinants, are classified as multidrug-resistant Hypervirulent Klebsiella pneumoniae (MDR-HvKp). Since the initial reports, there has been a concerning surge in infections caused by this pathotype globally. In this context, we aim to shed light on the evolutionary changes that have taken place in this relatively novel pathotype. Understanding these changes is crucial for devising diagnosis and targeted intervention strategies to mitigate the spread of MDR-HvKp infections.

Haploidentical stem cell transplantation (SCT) using post-transplantation cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis is a reasonable therapeutic option for patients who do not have a matched sibling donor. Between 2010 and June 2020, 257 patients underwent 269 Haploidentical transplantations, including 122 children. Indications included both malignant (56.8%) and non-malignant (43.2%) diseases. Conditioning regimens included both myeloablative (57.6%) and nonmyeloablative regimens (42.4%). Peripheral blood stem cells were the predominant graft source (96.2%). Based on the disease risk index, patients were classified into early-, intermediate-, and late-stage disease. Engraftment was seen in 205 patients (76.2%) whereas 39 (14.4%) died before engraftment and 23 (8.6%) had primary graft failure. The cumulative incidence of grade II-IV acute GVHD was 47.8% with a 23.9% incidence of grade III-IV acute GVHD. Chronic GVHD was seen in 41.9% with a 15.4% incidence of extensive chronic GVHD. More than 90% had at least 1 documented infection with a 44% incidence of bacterial, 71% viral, and 38% fungal infection. The 2-year overall survival is 40.5% ± 3.2% with a higher survival among children (48.2% ± 3.4%) compared to adults (34.2% ± 4.1%). Survival was poor with late-stage disease (23.6% ± 4.3%) compared to early- (62.5% ± 7.5%) and intermediate-stage (50.3% ± 4.3%). Factors adversely affecting survival included older age of patient (P = .007), late disease status (P = .000), nonmyeloablative conditioning regimen (P = .003), bone marrow as graft source (P = .006), presence of acute GVHD (P = .069), primary graft failure (P = .000), and presence of a documented bacterial (P = .000) and fungal infection (P = .000). On multivariate analysis, older age (P = .027), presence of acute GVHD (P = .033), documented bacterial infection (P = .000), documented fungal infection (P = .000) and primary graft failure (P = .012) continued to remain significant. Haploidentical SCT offers a reasonable chance of cure for patients with both malignant and nonmalignant hematological diseases. Strategies to reduce aGVHD and infection related mortality needs to be explored further.

Stenotrophomonas maltophiliais an emerging multi-drug resistant pathogen increasingly isolated in India. This study aimed to identify patients from whom Stenotrophomonas maltophiliahad been isolated and assess predictors of mortality in this population.

Following a relatively mild first wave of coronavirus disease 2019 (COVID-19) in India, a deadly second wave of the pandemic overwhelmed the healthcare system due to the emergence of fast-transmitting SARS-CoV-2 genetic variants. The emergence and spread of the B.1.617.2/Delta variant considered to be driving the devastating second wave of COVID-19 in India. Currently, the Delta variant has rapidly overtaken the previously circulating variants to become the dominant strain. Critical mutations in the spike/RBD region of these variants have raised serious concerns about the virus's increased transmissibility and decreased vaccine effectiveness. As a result, significant scientific and public concern has been expressed about the impact of virus variants on COVID-19 vaccines.

Recently, a novel species contaminansbelonging to the family Burkholderia cepaciacomplex (Bcc) is rising as a hospital pathogen. Detection of Burkholderia contaminans, a member of Bcc can be done only by MALDI TOF and sequencing techniques. We report the diagnostic challenges faced in an outbreak of bacteremia due to B. contaminansgrown in diltiazem vials.

Oral amoxicillin/clavulanate is a community workhorse antibiotic, routinely prescribed for respiratory tract infections, skin infections as well as urinary tract infections (UTIs). Multiple adult and paediatric dose formulations of amoxicillin/clavulanate are available in different parts of the world. In adult formulations, clavulanic acid dose is restricted to 125 mg because of tolerability issues. Despite its popular use for 40 years, few pharmacokinetic/pharmacodynamic (PK/PD) studies were undertaken to justify the doses and breakpoints currently in use for various infections. Clavulanate has a minimal role in the combination’s use for respiratory infections. In the context of rising extended spectrum beta-lactamase (ESBL) prevalence globally, empirical and overuse of orally administered amoxicillin/clavulanate may select resistance in Gram-negative pathogens. The susceptibility test methods and interpretive criteria differ between the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST). Third-generation oral cephalosporins such as ceftibuten or cefpodoxime can be combined with amoxicillin/clavulanate to tackle UTIs involving ESBL producing Escherichia coliand Klebsiellaspp. Clinicians who routinely prescribe amoxicillin/clavulanate in outpatient settings should be aware of potential benefits and limitations of this combination.

India is well known for the rampant growth of ESBLs that jeopardized the clinical utility of standalone beta-lactam. Pharmaceutical organizations fancied to rescue these beta-lactams by combining them with generic beta-lactamase inhibitors despite such combinations were never investigated in non-clinical or clinical studies. Lack of stringency in regulatory review practices allowed the market entry of these combinations. CSE 1034 (ceftriaxone, sulbactam and EDTA) and cefoperazone sulbactam are the most irrational antibiotics in clinical use. The effectiveness of such combinations relies on multiple factors such as relative beta-lactamase stability of the standalone beta-lactam, the inhibitory potency of the beta-lactamase inhibitor and more importantly the adequacy of the dose incorporated in the formulation. Unfortunately, none of the unconventional BL-BLI inhibitor combinations marketed in India has been subjected to such evaluations. Therefore, their therapeutic utility is uncertain. Besides questionable therapeutic utility, sub-optimal exposures would lead to the selection of resistant clones.

Introduction: Available evidence from observational studies and meta-analyses has highlighted an increased mortality in patients with carbapenem-resistant Klebsiella pneumoniae(CRKP) bloodstream infections (BSI) compared with their carbapenem-susceptible (CSKP) counterparts, but the exact reasons for this outcome difference are still to be determined. Methods: We updated the search of a previous meta-analysis through four databases up to April 2018. A two-stage individual-patient data (IPD) meta-analysis was conducted, building an adjusting model to account for age, comorbidities and activity of empirical and targeted antimicrobial therapy. The protocol was registered on PROSPERO (identifier: CRD42018104256). Results: IPD data were obtained from 14 out of 28 eligible observational studies. A total of 1952 patients were investigated: 1093 in the CRKP group and 859 in the CSKP group. Patients with CRKP-BSI had a twofold risk of death compared with CSKP-infected patients [adjusted odds ratio (aOR) 2.17; 95% confidence interval (CI) 1.56–3.04; I2= 44.1%]. Mortality was higher in patients with CRKP BSI, in both the subgroup of absent/inactive (aOR 1.75; 95% CI 1.24–2.47; I2= 0) and of active initial therapy (aOR 2.66; 95% CI 1.70–4.16; I2= 16%) as well as in case of active targeted therapy (aOR 2.21; 95% CI 1.36–3.59; I2= 58%). Conclusion: Resistance to carbapenem is associated with worse outcome in patients with BSI by Klebsiella pneumoniaeeven adjusting for comorbidities and treatment appropriateness according to in vitro activity of empirical and targeted therapy. This applies to a scenario dominated by colistin-based therapies for CRKP. Further studies are needed to compare the mortality difference between CRKP and CSKP cases in the light of new anti-CRKP antimicrobials.

The treatment of urinary tract infections (UTIs) has been complicated by the emergence of multidrug-resistant, β-lactamase-expressing pathogens. As a result of the limited treatment options, patients often require hospitalization and intravenous therapy. In essence, a strong unmet need for oral antibiotics, active against extended-spectrum β-lactamase (ESBL) uropathogens has emerged. Oral carbapenems (tebipenem and sulopenem) and oral cephalosporin/β-lactamase inhibitor combinations are in various stages of clinical development for the treatment of uncomplicated and complicated UTI. Tebipenem, if approved, will be the first oral treatment for complicated UTI while sulopenem will be for uncomplicated UTI. The β-lactamase inhibitors ETX0282, VNRX7145, ARX1796, and QPX7728 are combined with cefpodoxime proxetil or ceftibuten that achieve favorable exposures in urine compared to other uropathogen-active oral cephalosporins. The combination ceftibuten-QPX7728 has potential broad-spectrum coverage against carbapenemase producers including metallo β-lactamase producers. Other novel combinations, namely cefpodoxime/ETX0282, ceftibuten/VNRX-7145, and ceftibuten/ARX1796, have also demonstrated excellent activity against Klebsiella pneumoniaecarbapanemase (KPC) and OXA-48-like producers. All these agents, upon their arrival for commercial use, would strengthen the outpatient therapy.

Background:Aminoglycoside resistance is a growing challenge, and it is commonly mediated by the aminoglycoside-modifying enzymes (AMEs), followed by 16S rRNA methyl transferase. Plazomicin, a novel aminoglycoside agent approved by the Food and Drug Administration for complicated urinary tract infections is proven to overcome resistance mediated by AMEs but not due to 16S rRNA methyl transferase (16SRMTases). We undertook this study to predict the efficacy of plazomicin in India based on the antimicrobial resistance profile derived from whole-genome sequencing (WGS). Methodology:A total of 386 clinical isolates of Escherichia coli, Klebsiella pneumoniaeand Acinetobacter baumanniisubjected to WGS were screened for aminoglycoside-resistance mechanisms such as AMEs and 16SRMTases and its association with carbapenemases. Results:AMEs was present in all E. coli, A. baumanniiand in 90% of K. pneumoniae. In addition, up to 47% of E. coliand 38% of K. pneumoniaeco-carried 16SRMTases with AMEs genes. However, A. baumanniishowed 87% of isolates co-harbouring 16SRMTase. blaNDM, blaOxa-48-like and blaOxa-23-like were the most predominant carbapenemases in E. coli, K. pneumoniaeand A. baumannii, respectively. Notably, 48% of NDM-producing E. coliand 35% of Oxa-48-like producing K. pneumoniaewere identified to co-harbour AMEs + RMTAses, where plazomicin may not be useful. Conclusion:Overall, 53%, 62% and 14% of carbapenemase-producing E. coli, K. pneumoniaeand A. baumanniiharbours only AMEs, indicating the role of plazomicin use. Plazomicin can be used both for ESBLs as “carbapenem-sparing agent” and carbapenemase producers as “colistin-sparing agent.” For optimal use, it is essential to know the molecular epidemiology of resistance in a given geographical region where plazomicin empirical therapy is considered.

AbstractObjective:Resistance to colistin, a last resort antibiotic, has emerged in India. We investigated colistin-resistant Klebsiella pneumoniae(ColR-KP) in a hospital in India to describe infections, characterize resistance of isolates, compare concordance of detection methods, and identify transmission events.Design:Retrospective observational study.Methods:Case-patients were defined as individuals from whom ColR-KP was isolated from a clinical specimen between January 2016 and October 2017. Isolates resistant to colistin by Vitek 2 were confirmed by broth microdilution (BMD). Isolates underwent colistin susceptibility testing by disk diffusion and whole-genome sequencing. Medical records were reviewed.Results:Of 846 K. pneumoniaeisolates, 34 (4%) were colistin resistant. In total, 22 case-patients were identified. Most (90%) were male; their median age was 33 years. Half were transferred from another hospital; 45% died. Case-patients were admitted for a median of 14 days before detection of ColR-KP. Also, 7 case-patients (32%) received colistin before detection of ColR-KP. All isolates were resistant to carbapenems and susceptible to tigecycline. Isolates resistant to colistin by Vitek 2 were also resistant by BMD; 2 ColR-KP isolates were resistant by disk diffusion. Moreover, 8 multilocus sequence types were identified. Isolates were negative for mobile colistin resistance (mcr) genes. Based on sequencing analysis, in-hospital transmission may have occurred with 8 case-patients (38%).Conclusions:Multiple infections caused by highly resistant, mcr-negative ColR-KP with substantial mortality were identified. Disk diffusion correlated poorly with Vitek 2 and BMD for detection of ColR-KP. Sequencing indicated multiple importation and in-hospital transmission events. Enhanced detection for ColR-KP may be warranted in India.

There is a high diversity of beta-lactamases in gram negative pathogens, making them difficult to treat. In the presence of OXA-1 and ampC, PTZ is no longer clinically relevant when treating Enterobacterales expressing ESBLs. Further, MBL infections are often treated with ceftazidime/avibactam and aztreonam in combination. It has recently been reported that NDM-expressing E. coli isolates co-harboring NDM developed resistance to this triple combination.

We evaluated the performance of automated susceptibility testing for piperacillin/tazobactam (PTZ) MICs against the reference microbroth dilution method. The Minimum Inhibitory Concentration of PTZ against a clinical isolate of Klebsiella pneumoniaewas determined by reference broth micro-dilution method in 10 replicates which yielded a modal MIC of 16 mg/L (susceptible dose-dependent). Out of 434 laboratories who obtained MIC of 16 mg/L correctly, only 301 interpreted the result as susceptible dose dependent as per 2022 revised CLSI criteria. Educating the clinical laboratories in validating AST methods as per latest CLSI guidelines is of utmost important.

Treatment of antibiotic-resistant Gram-positive infections (GPIs), including methicillin-resistant Staphylococcus aureus(MRSA) is becoming increasingly difficult, particularly in patients with multiple co-morbidities who require antibiotics with greater safety and a consistent pharmacokinetic/pharmacodynamic (PK/PD) profile. Such difficult-to-treat GPIs are often associated with poor outcomes, extended hospital stay and increased expenditure. This can be partly attributed to the limited safety and aberrant PK/PD profile of existing anti-MRSA antibiotics. In this context, intravenous levonadifloxacin and its oral prodrug alalevonadifloxacin are novel anti-MRSA antibiotics that have significant advantages over conventional anti-Gram-positive antibiotics. The purpose of this paper was to generate a consensus on the optimal use of levonadifloxacin and alalevonadifloxacin for tackling resistant Gram-positive infections in patients with multiple co-morbidities.

Burkholderia cepacia complex (BCC) is a well-recognized cause of nosocomial infections. We describe here a young healthy male who presented with fever and chest pain with ECG changes of acute pericarditis. Two sets of blood cultures at separate timings grew gram negative bacilli identified as BCC by molecular methods. The patient responded to intravenous ceftazidime despite high ceftazidime MIC's. The source of infection was probably contaminated nasal spray/nasal saline wash which he used after a balloon sinoplasty procedure one month ago. Issues related to accurate identification and susceptibility testing of BCC are also discussed.

Staphylococcus aureusis of significant clinical concern in both community- and hospital-onset infections. The key to the success of S. aureusas a pathogen is its ability to swiftly develop antimicrobial resistance. Methicillin-resistant S. aureus(MRSA) is not only resistant to nearly all beta-lactams but also demonstrates resistance to several classes of antibiotics. A high prevalence of MRSA is seen across worldwide. For many decades, vancomycin remained as gold standard antibiotic for the treatment of MRSA infections. In the past decades, linezolid, daptomycin, ceftaroline and telavancin received regulatory approval for the treatment of infections caused by resistant Gram-positive pathogens. Although these drugs may offer some advantages over vancomycin, they also have significant limitations. These includes vancomycin’s slow bactericidal activity, poor lung penetration and nephrotxicity;linezolid therapy induced myelosuppression and high cost of daptomycin greatly limits their clinical use. Moreover, daptomycin also gets inactivated by lung naturally occurring surfactants. Thus, currently available therapeutic options are unable to provide safe and efficacious treatment for those patients suffering from hospital-acquired pneumonia, bloodstream infections (BSIs), bone and joint infections and diabetic foot infections (DFI). An unmet need also exists for a safe and efficacious oral option for switch-over convenience and community treatment. Herein, the review is intended to describe the supporting role of anti-staphylococcal antibiotics used in the management of S. aureusinfections with a special reference to levonadifloxacin. Levonadifloxacin and its prodrug alalevonadifloxacin are novel benzoquinolizine subclass of quinolone with broad-spectrum of anti-MRSA activity. It has been recently approved for the treatment of complicated skin and soft-tissue infection as well as concurrent bacteraemia and DFI in India.

To investigate the epidemiology of invasive pneumococcal disease (IPD), prevalent serotypes, and pattern of antimicrobial resistance (AMR) in Indian adults.

•Colonisation virulence factor sasXhas contributed to successful establishment of MRSA ST239 clone in Asia.•sesI, an sasXhomologue native to S. epidermidis, was identified in MRSA ST239 strain.•As the sasXvirulence gene is located on a bacteriophage, the probability of dissemination is high.•This highlights the dissemination of sesIfrom S. epidermidisto MRSA strains.

Background:Pneumococcal pneumonia is one of the major causes of mortality in children less than 5 years in Asia, especially in India. Available PCVs have less serotype coverage in India compared to western countries. Moreover, the baseline pneumococcal serotype and sequence type data is limited and available data doesn’t represent the entire India. With this background we aimed to characterize invasive and carriage isolates of S. pneumoniaefrom a tertiary care hospital in South India. Materials and Methods:A total of 221 S. pneumoniaeisolates, invasive (n=138) and carriage (n=83) between the time period of 2012-2018 were included. Isolates was identified and confirmed using standard laboratory protocols. Serotyping was performed by Customized sequential multiplex PCR and MLST as described in www.pubmlst.org. Results:The major serotypes were 19F, 6B, 14, 6A and 19A and the sequence types (ST) were ST63, 236 and 230. Predominant STs in invasive was ST 63 whereas in carriage were ST4894 and 1701. High level ST diversity in carriage was observed. Majority of the STs were SLVs or DLVs of previously reported STs or PMEN clones. Phylogenetic analyses of the STs revealed gradual expansion of three PMEN CCs CC320, 63 and 230. Conclusion:The vaccine serotypes were the predominant ones found to be associated with IPD, PMEN clones, new STs and antimicrobial resistance. Accordingly, PCV13 is expected to provide invasive serotype coverage of 75% in Indian children less than 5 years. This study provides baseline serotype and sequence type data prior to the introduction of PCV in South India.

Introduction:Antimicrobial-resistant HAI (Healthcare associated infection) are a global challenge due to their impact on patient outcome. Implementation of antimicrobial stewardship programmes (AMSP) is needed at institutional and national levels. Assessment of core capacities for AMSP is an important starting point to initiate nationwide AMSP. We conducted an assessment of the core capacities for AMSP in a network of Indian hospitals, which are part of the Global Health Security Agenda-funded work on capacity building for AMR-HAIs. Subjects and Methods:The Centers for Disease Control and Prevention’s core assessment checklist was modified as per inputs received from the Indian network. The assessment tool was filled by twenty hospitals as a self-administered questionnaire. The results were entered into a database. The cumulative score for each question was generated as average percentage. The scores generated by the database were then used for analysis. Results and Conclusion:The hospitals included a mix of public and private sector hospitals. The network average of positive responses for leadership support was 45%, for accountability; the score was 53% and for key support for AMSP, 58%. Policies to support optimal antibiotic use were present in 59% of respondents, policies for procurement were present in 79% and broad interventions to improve antibiotic use were scored as 33%. A score of 52% was generated for prescription-specific interventions to improve antibiotic use. Written policies for antibiotic use for hospitalised patients and outpatients were present on an average in 72% and 48% conditions, respectively. Presence of process measures and outcome measures was scored at 40% and 49%, respectively, and feedback and education got a score of 53% and 40%, respectively. Thus, Indian hospitals can start with low-hanging fruits such as developing prescription policies, restricting the usage of high antibiotics, enforcing education and ultimately providing the much-needed leadership support.

ABSTRACTShigellais the major cause of bacillary dysentery worldwide, especially in developing countries. There are several virulence factors essential for the organism to be virulent which are generally present in the virulence plasmid and on chromosomal pathogenicity islands. The present study was undertaken to determine the virulence gene profile of Shigella sppisolated from a clinical specimen and to study their significant association with common clinical symptoms and antimicrobial resistance. Sixty Shigellawhole genome sequences, including 22 S. flexneri, 14 S. sonnei, 17 S. boydiiand 7 S. dysenteriaewere analyzed for the presence of virulence genes. The gene found predominantly in this study were ipaH (90%) followed by sigA (83%), and lpfA (78%) respectively. The virulence genes were significantly higher in S. flexneri, particularly in serotype 2 compared to S. sonnei. Interestingly, a significant association was observed between sigA gene and fever whereas sepA and sigA were found to be associated with diarrhea. Among the studied Shigellaisolates, the presence of virulence genes was found higher in isolates resistant to more than three antibiotic classes. The present work revealed the varying incidence of virulence determinants among different Shigellaserogroups and shows their contribution to disease severity.

AbstractObjective:Antimicrobial stewardship programs (ASPs) are effective in developed countries. In this study, we assessed the effectiveness of an infectious disease (ID) physician–driven post-prescription review and feedback as an ASP strategy in India, a low middle-income country (LMIC).Design and setting:This prospective cohort study was carried out for 18 months in 2 intensive care units of a tertiary-care hospital, consisting of 3 phases: baseline, intervention, and follow up. Each phase spanned 6 months.Participants:Patients aged ≥15 years receiving 48 hours of study antibiotics were recruited for the study.Methods:During the intervention phase, an ID physician reviewed the included cases and gave alternate recommendations if the antibiotic use was inappropriate. Acceptance of the recommendations was measured after 48 hours. The primary outcome of the study was days of therapy (DOT) per 1,000 study patient days (PD).Results:Overall, 401 patients were recruited in the baseline phase, 381 patients were recruited in the intervention phase, and 379 patients were recruited in the follow-up phase. Antimicrobial use decreased from 831.5 during the baseline phase to 717 DOT per 1,000 PD in the intervention phase (P< .0001). The effect was sustained in the follow-up phase (713.6 DOT per 1,000 PD). De-escalation according to culture susceptibility improved significantly in the intervention phase versus the baseline phase (42.7% vs 23.6%; P< .0001). Overall, 73.3% of antibiotic prescriptions were inappropriate. Recommendations by the ID team were accepted in 60.7% of the cases.Conclusion:The ID physician–driven implementation of an ASP was successful in reducing antibiotic utilization in an acute-care setting in India.

Purpose:Hospital outbreaks are observed increasingly worldwide with various organisms from different sources such as contaminated ultrasound gel, intravenous (IV) fluids and IV medications. Among these, ultrasound gel is one of the most commonly reported sources for Burkholderia cepaciacomplex (Bcc) outbreaks. In this study, we describe our experience on investigation and the management of Bcc bacteraemia outbreak due to contaminated ultrasound gel from a tertiary care centre, South India. Materials and Methods:Over a 10-day period in October 2016, seven children in our Paediatric intensive care unit (ICU) were found to have bacteraemia with Bcc isolated from their blood culture. Repeated isolation of the same organism with similar antimicrobial susceptibility pattern over a short incubation period from the same location, confirmed the outbreak. An active outbreak investigation, including environmental surveillance, was carried out to find the source and control the outbreak. Isolates were subjected to multi-locus sequence typing (MLST) and global eBURST (goeBURST) analysis. Results:Environmental surveillance revealed contaminated ultrasound gel as the source of infection. MLST and goeBURST analysis confirmed that the outbreak was caused by a novel sequence type 1362 with the same clonal complex CC517. The outbreak was controlled by stringent infection control measures, withdrawal of contaminated ultrasound gel from regular usage and implementing the practice of using ultrasonogram (USG) probe cover for USG screening and guided procedures. Conclusion:This report highlights the importance of early identification of an outbreak, prompt response of the ICU and infection control teams, sound environmental and epidemiological surveillance methods to identify the source and stringent infection control measures to control the outbreak. Contaminated ultrasound gel can be a potential source for healthcare-associated infection, which cannot be overlooked.

Background:Non-typhoidal Salmonella(NTS) infection is a serious public health problem globally. Although NTS infections are self-limited, antimicrobial therapy is recommended for severe infections and immunocompromised patients. Antimicrobial resistance (AMR) in these pathogens further limits its therapeutic options. Here, we report an incidence of ceftriaxone resistance in NTS over the past 9 years in a southern Indian region. Materials and Methods:Molecular mechanisms of resistance in ceftriaxone-resistant NTS have been tested by both phenotypic and molecular methods. Minimum inhibitory concentration was determined by the E-test and broth microdilution method. AMR gene markers of β-lactamases such as AmpCs (blaMOX, blaCMY, blaDHA, blaFOX, blaACCand blaACT) and extended-spectrum β-lactamases (ESBLs) (blaSHV, blaTEM, blaVEB, blaPER, blaCTXM-1 like, blaCTXM-2like, blaCTXM-8like, blaCTXM-9likeand blaCTXM-25like) were screened. The presence of IncH12 and IncI1 plasmid was also analysed. Results:The study reports a 5% prevalence of ceftriaxone resistance in NTS. The most common serogroup was SalmonellaGroup B followed by SalmonellaGroup E and Salmonellagroup C1/C2. The occurrence of blaCTX-M-1, blaTEM, blaCMYand blaSHVgenes was observed in 54%, 54%, 48% and 3% of the isolates, respectively. Interestingly, few isolates carried dual resistance genes (ESBLs and AmpCs). IncH12 and IncI1 plasmid was identified in isolates carrying ESBL and AmpC genes, respectively. Conclusion:This study shows that ceftriaxone resistance is mainly mediated by β-lactamases such as ESBL and AmpC. As the incidence of ceftriaxone resistance is rising gradually over the years, it is imperative to monitor the AMR in this species.

India is one among the four Asian countries with the greatest number of deaths due to pneumococcal infection among children under 5 years. pneumococcal conjugate vaccine (PCV) has been introduced in a phased manner in five major Indian states. Ambiguity remains in choosing the appropriate type of PCV and optimum schedule with maximum effectiveness specific for each country. Here, we discuss the evidences with respect to serotype coverage, immunogenicity, reactogenicity and dosage schedule for introduction of PCV13 in India. In addition, the expected PCV impact and the challenges are detailed. PCV13 is expected to provide >75% serotype coverage for invasive pneumococcal disease (IPD) serotypes in Indian children combined with the replacement by nonvaccine serotypes which is unpredictable due to lack of complete data. Nasopharyngeal (NP) surveillance is easy, feasible and can replace IPD surveillance in resource-poor settings. Continuous IPD as well as NP surveillance in all the regions are necessary to assess the impact of PCV in India.

•Antimicrobial resistance is a growing problem in Shigellaspp., particularly to fluoroquinolones and cephalosporins.•Plasmids harbouring antimicrobial resistance determinants in clinical strains are a major concern worldwide.•IncF-type plasmids in clinical multidrug-resistant Shigella flexneriisolates were identified.•Sequencing of plasmid pSF470 revealed the presence of resistance genes to clinically important antimicrobial agents.

•Raw food samples (n=110) from Chennai, India, tested for colistin-resistant (Col-R) bacteria.•51 (46.4%) of the tested food samples had Col-R bacteria.•The mcr-1gene was identified in Col-R Escherichia coli.•Mutations and insertional inactivation of the mgrBgene identified in Klebsiellaspp.

Introduction: Heteroresistant vancomycin-intermediate Staphylococcus aureus(hVISA) bacteremia may result in clinical failure of vancomycin therapy, together with prolonged infection and hospitalization. This clinical problem has resulted in a search for more effective treatment options. The current study was designed to further investigate the synergistic effect of oxacillin plus vancomycin against methicillin-resistant S. aureus(MRSA) and hVISA using checkerboard and time-kill assays. Methods: Non-duplicate S. aureusisolates including hVISA (n= 29), MRSA (n= 10) and methicillin susceptible S. aureus(MSSA, n= 11) were used for combinational testing using checkerboard and time-kill assays. Results: Twenty-one isolates, 15 hVISA and 6 MRSA, showed synergy between oxacillin and vancomycin by checkerboard assay with fractional inhibitory concentration indices of ≤ 0.5. The addition of oxacillin to vancomycin resulted in a reduction in baseline vancomycin MIC from 1–2 to 0.06–0.5 µg/ml against MRSA and hVISA isolates. In the time-kill assay, the combination of oxacillin and vancomycin resulted in synergistic activity against hVISA (n= 23) and MRSA (n= 7) isolates. Regrowth was observed in six hVISA isolates exposed to combination in the time-kill assay, but none of them reached the original inoculum density at 24 h. All re-growth isolates showed a onefold increase in vancomycin MIC (from 1 to 2 µg/ml) and were re-confirmed as hVISA using the population-analysis profile experiment. Overall, for hVISA and MRSA, the combination of oxacillin plus vancomycin had greater antibacterial effect than each individual drug alone. Conclusion: The present study showed the potential activity of vancomycin plus oxacillin combination against hVISA and MRSA isolates. Further, continued evaluation of this combination is warranted and may have therapeutic benefits in treating complicated MRSA infections.

ABSTRACTNon-typhoidal Salmonella(NTS) are foodborne pathogens that are responsible for self-limiting gastroenteritis in humans. The present study aims at the molecular characterisation and comparative genomics of Salmonella entericaserovar Senftenberg strain P5558 isolated from the pus samples of a patient suffering from stump infection. The isolate was subjected to serotyping and antimicrobial susceptibility test to understand the phenotypical characteristics. Whole genome sequencing (WGS) was carried out and comparative genomics using computational tools showed the antimicrobial resistance and virulence gene profile of the isolates from the genome sequence data. Typing experiments confirmed that the isolate belong to S. Senftenberg with sequence type ST14. Resistance against β-lactams is associated with the presence of blaTEM-1, blaOXA-9, blaCMY-2and blaNDM-1genes. Similarly resistance to aminoglycoside was associated with five aminoglycoside modifying enzymes aac(6ʹ)-Ia, aac(6ʹ)-Ib, aph(3ʹ)-Ib, aph(6ʹ)-Iband ant(3ʹʹ)-Ia, sulfonamide with sul-1and sul-2and chloramphenicol with florRgene. Substitutions in gyrA(S83Y, D87G) and parC(S80I) genes found to be the reason for fluoroquinolone resistance. The plasmid profiling showed the isolate has four resistance plasmids in which plasmid p5558-NDM (IncA/C) harbours major resistance genes including blaNDM-1and blaCMY-2.Determination of virulence gene profile revealed that the genome carries all major Salmonellapathogenicity islands and virulence factors. From our findings it is clear that the isolate possess characteristic pathogenicity islands (SPI 1–6, 13, 14), major virulence factors and acquired resistance genes. Comparative analysis suggests the evolution and distribution of the MDR gene encoding plasmids in NTS.

Tigecycline is a reserve antibiotic increasingly used for the treatment of multidrug-resistant bacteria, especially Klebsiella pneumoniaeand Acinetobacter baumannii. At present, there are concerns regarding the testing and interpretation of tigecycline susceptibility to bugs such as K. pneumoniaeand A. baumannii, which limit clinicians in appropriate usage. Use of appropriate method for testing such as broth microdilution is essential. In addition, tigecycline susceptibility testing is a challenge due to inconsistent results from various antimicrobial susceptibility testing automated platforms. There is a great need to define a suitable methodology along with interpretive criteria, especially for K. pneumoniaeand A. baumannii. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Food and Drug Administration (FDA) breakpoints show wide variation and are defined for different set of organisms. Non-species-related pharmacokinetic/pharmacodynamic (PK/PD) breakpoints defined by the EUCAST can be used for organisms such as K. pneumoniaeand A. baumannii.

Antimicrobial resistance is on the rise across the globe. Increasing incidence of infections due to carbapenem resistance organisms is becoming difficult to treat, due to the limited availability of therapeutic agents. Very few agents such as colistin, fosfomycin, tigecycline and minocycline are widely used, despite its toxicity. However, with the availability of novel antimicrobials, beta-lactam/beta-lactamase inhibitor-based and non-beta-lactam-based agents could be of great relief. This review covers three important aspects which include (i) current management of carbapenem-resistant infections, (ii) determination of specific types of carbapenemases produced by multidrug-resistant and extensively drug-resistant Gram-negative pathogens and (iii) the currently available novel beta-lactam/beta-lactamase inhibitors and non-beta-lactam-based agents’ laboratory findings, clinical outcome and implications.

Introduction:Carbapenem resistance (CR) in Klebsiella pneumoniaeis mainly mediated by blaNDM and blaOXA-48 carbapenemases. Newer Food and Drug Administration-approved antimicrobial ceftazidime/avibactam (C/A) has a potent activity against blaOXA-48-like producers. However, its activity is limited in organisms co-producing blaNDM and blaOXA-48-like. Addition of aztreonam (ATM) to C/A potentially expands the spectrum of coverage for carbapenemase co-producers. With this, we aimed to determine the synergistic activity of combination of C/A plus ATM against blaNDM, blaOXA-48-like and co-producers of blaNDM + blaOXA-48-like producing CR Klebsiella pneumoniae(CRKp). Materials and Methods:A total of 12 isolates of CRKp-harbouring genes encoding blaNDM and blaOXA-48-like were tested. Minimum inhibitory concentrations (MICs) were determined for several antimicrobial agents, including C/A (0.5–8 μg/ml) by broth microdilution method. Checkerboard assay was performed for the combination of C/A plus ATM at varying concentrations. Fold differences in the MIC of C/A with and without addition of ATM were determined to infer synergistic effects. Results:MIC of C/A and ATM ranged from 0.5 to >8 μg/ml and 64 to 2048 μg/ml, respectively. Two isolates were susceptible to C/A with MIC of 0.5 and 1 μg/ml, while others were resistant with MIC of >8 μg/ml. Synergistic effects of >8-fold MIC difference in C/A MIC were noted with addition of ATM at 4 μg/ml. This was observed for all CRKp with profiles of blaNDM, blaOXA-48-like and co-producers of blaNDM + blaOXA-48-like genes, which was a promising effect. Notably, all five of the colistin-resistant CRKp were inhibited with >8-fold MIC difference in the combination of C/A plus ATM at 4 μg/ml. Conclusion:With the increasing burden of CRKp, the use of C/A with ATM combination seems to be very promising, especially for blaNDM, blaOXA-48-like and co-producers of blaNDM + blaOXA-48like carbapenemases.

Invasive group B Streptococcal disease (iGBS) is an important cause of morbidity and mortality in neonates for which the development of an efficacious vaccine remains a global health imperative. The knowledge about the serotype distribution of iGBS is important component for formulation of Capsular polysaccharide (CPS)-based vaccine. However, there were absolute lack of information on serotype distribution in invasive GBS isolates from Indian subcontinent. Methods This study has assessed the serotype distribution and antimicrobial susceptibility profile of invasive group B streptococcal isolates for a period of 13 years from 2009 to 2022 from a tertiary care Center in South India. A total of 155 iGBS isolates were subjected to serotyping by conventional multiplex PCR for identification of all ten GBS serotype. Antimicrobial susceptibility profile and demographic details were extracted from microbiological records. Results Overall, the most common serotype causing invasive GBS were Ia (29%), V (26%), III (15%), II (12%), VI (6%), VII (5%) and Ib (5%). Serotypes IV, VIII and XI were not detected. Among the early-onset iGBS, the common serotype were Ia (36%), V (27%), and III (8%). In late onset iGBS, Serotype III (44%) was predominant. The common serotype in adults were Serotype V (31%) and III (20%). All the invasive GBS isolates were susceptible for penicillin (100%), but the susceptibility for clindamycin and erythromycin were 72% and 80% respectively. Conclusion The serotype distribution of invasive Group B streptococcal isolates from India suggest that hexavalent group B CPS vaccine will cover only 90% of GBS isolates causing invasive disease among the infants in India. Continued surveillance monitoring for serotype distribution and antimicrobial resistance patterns for iGBS are warranted to make public health interventions.

Escherichia coliis regarded as one of the most commonly isolated Gram-negative pathogens from bloodstream infections. Increasing antimicrobial resistance (AMR) among E. coliis a threat to disease management as well as further dissemination of AMR genes to other clinically important pathogens. Here we report the genome of a multidrug-resistant (MDR) E. coli(BA22372) from a bloodstream infection belonging to ST410 B4/H24RxC subtype from India.

Elizabethkingiaspp. are Gram-negative, glucose-non-fermenting bacilli that are ubiquitous in natural environments such as soil, plant and water sources. Besides environmental sources, the bacterium can be found in hospital environments, particularly medical equipment and reagents. Here we report the draft genome sequence of an Elizabethkingia anophelisisolate from a blood culture.

Recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and subsequent containment procedures have impacted the world as never seen before. Therefore, there is considerable curiosity about the genome evolution related to the origin, transmission and vaccine impact of this virus. We have analysed genome sequences of SARS-CoV-2 isolated from Indian patients to gain an in-depth understanding of genomic evolution and transmission in India. Phylogenetic analysis and mutation profiling revealed major lineages being evolved by characteristic mutations. As the mutation frequency in spike protein is comparatively lesser, the candidate vaccines expected to have wide coverage worldwide including India.

•Molecular characterisation of community-acquired MRSA with reduced teicoplanin susceptibility from a bacteraemia patient.•Panton–Valentine leukocidin and staphylococcal enterotoxin genes were carried on the same prophage (phiSa119).•Teicoplanin resistance may occur due to mutations in the tcaRABsystem.

Background:Pseudomonas aeruginosais one of the most common opportunistic pathogens that cause severe infections in humans. The burden of carbapenem resistance is particularly high and is on the rise. Very little information is available on the molecular mechanisms and its clonal types of carbapenem-resistant P. aeruginosaseen in Indian hospitals. This study was undertaken to monitor the β-lactamase profile and to investigate the genetic relatedness of the carbapenemase-producing (CP) P. aeruginosacollected across different hospitals from India. Materials and Methods:A total of 507 non-duplicate, carbapenem-resistant P. aeruginosaisolated from various clinical specimens collected during 2014–2017 across seven Indian hospitals were included. Conventional multiplex polymerase chain reaction for the genes encoding beta-lactamases such as extended-spectrum beta-lactamase (ESBL) and carbapenemase were screened. A subset of isolates (n= 133) of CP P. aeruginosawere genotyped by multilocus sequence typing (MLST) scheme. Results:Of the total 507 isolates, 15%, 40% and 20% were positive for genes encoding ESBLs, carbapenemases and ESBLs + carbapenemases, respectively, whilst 25% were negative for the β-lactamases screened. Amongst the ESBL genes, blaVEBis the most predominant, followed by blaPERand blaTEM, whilst blaVIMand blaNDMwere the most predominant carbapenemases seen. However, regional differences were noted in the β-lactamases profile across the study sites. Genotyping by MLST revealed 54 different sequence types (STs). The most common are ST357, ST235, ST233 and ST244. Six clonal complexes were found (CC357, CC235, CC244, CC1047, CC664 and CC308). About 24% of total STs are of novel types and these were found to emerge from the high-risk clones. Conclusion:This is the first large study from India to report the baseline data on the molecular resistance mechanisms and its association with genetic relatedness of CP P. aeruginosacirculating in Indian hospitals. blaVIM- and blaNDM-producing P. aeruginosais the most prevalent carbapenemase seen in India. Majority of the isolates belongs to the high-risk international clones ST235, ST357 and ST664 which is a concern.

Antimicrobial resistance (AMR) is a major public health concern across the globe, and it is increasing at an alarming rate. Multiple classes of antimicrobials have been used for the treatment of infectious diseases. Rise in the AMR limits its use and hence the prerequisite for the newer agents to combat drug resistance. Among the infections caused by Gram-negative organisms, beta-lactams are one of the most commonly used agents. However, the presence of diverse beta-lactamases hinders its use for therapy. To overcome these enzymes, beta-lactamase inhibitors are being discovered. The aim of this document is to address the burden of AMR in India and interventions to fight against this battle. This document addresses and summarises the following: The current scenario of AMR in India (antimicrobial susceptibility, resistance mechanisms and molecular epidemiology of common pathogens); contentious issues in the use of beta-lactam/beta-lactamase inhibitor as an carbapenem sparing agent; role of newer beta-lactam/beta-lactamase inhibitor agents with its appropriateness to Indian scenario and; the Indian Council of Medical Research interventions to combat drug resistance in terms of surveillance and infection control as a national response to AMR. This document evidences the need for improved national surveillance system and country-specific newer agents to fight against the AMR.

Infections due to Pseudomonas aeruginosais a major health concern, especially hospital-acquired infections, in critically ill individuals. Antimicrobial resistance (AMR) increases the morbidity and mortality rates associated with pseudomonal infections. In this review, we aim to address two major aspects of P. aeruginosa. The first part of the review will focus on the burden of AMR and its prevailing mechanisms seen in India, while the second part will focus on the challenges and approaches in the management with special emphasis on the role of newer antimicrobial agents.

Brucellosis, a common zoonosis, is under reported in India despite its endemicity and increased exposure to livestock among the population. This study was conducted to determine the clinical manifestations, antibiotic susceptibility pattern, treatment and outcome of culture confirmed brucellosis. Adult patients with culture confirmed brucellosis who presented to a large teaching hospital in South India between 2009 and 2015 were included. A diagnosis of brucellosis was confirmed on automated culture. Clinical profile, laboratory parameters, drug susceptibility, treatment and outcome were documented by reviewing the medical records. The cohort comprised of 22 patients with mean ± SD age of 42 ± 13 years. Twenty one (95.5%) was male. Thirteen (59%) patients were from rural area and risk of acquisition of brucellosis including occupational exposure or consumption of unpasteurized milk was evident in 16 (72.7%) patients. The mean duration of symptoms before presentation was 54.5 ± 52 days. The commonest clinical presentation was prolonged fever without a definite focus in 18 patients (82%), whereas 2 (9%) patients had osteoarticular involvement and one patient (4.5%) each had genital involvement and endocarditis. Eighteen patients (82%) with uncomplicated brucellosis were treated with aminoglycoside and doxycycline for 6 weeks. There was no relapse or mortality at 18 ± 9 months of follow up. Brucellosis in this cohort had acute or subacute presentation with prolonged fever and bacteremia. High index of clinical suspicion based on significant epidemiological history along with automated blood culture improves the efficiency of diagnosis. Cure with lack of relapse among these cases suggests a combination therapy with doxycycline and aminoglycoside is highly effective for the treatment.