Recent Submissions

  • Mini-review: Clostridioides difficile epidemiology in India.

    Ambalkar, Shrikant
    Clostridioides difficile infection (CDI) continues to affect hospitalized patients and community populations worldwide. In contrast to the substantial resources invested in the diagnosis and prevention of CDI in high-income countries, this anaerobic toxigenic bacterium has been largely overlooked in low-and-middle-income countries (LMICs) such as India, where there remains a paucity of epidemiologic data evaluating the burden of CDI. Extensive multi-institutional studies describing C. difficile epidemiology in India have not yet been performed. Given recent economic growth in many Asian countries, with aging populations, increased access to healthcare and widespread inappropriate use of antimicrobials, C. difficile is likely to be highly prevalent and causing significant disease burden. Greater efforts are required to enhance awareness of this neglected pathogen, through educating healthcare practitioners to test for CDI. There is also an urgent need to strengthen laboratory capacity, and ideally establish a national reference laboratory, to help facilitate a greater understanding of the molecular epidemiology of CDI in India and other LMICs. This mini-review aims to summarize the existing research evaluating the burden of CDI in humans and the environment in India.
  • Drains and the periphery of the water system - what do you do when the guidance is outdated?.

    Weinbren, Michael
    Summary The periphery of the water system (defined as the last 2 m of pipework from an outlet and ensuing devices including drainage), is the juncture of multiple inherent risks: the necessity to use materials with higher risk of biofilm formation, difficulty in maintaining safe water temperatures, a human interface with drainage systems, poor design, poor layout and use by staff. Add to this risk a large new healthcare facility capital build programme in England, outdated guidance and bacteria emanating from drainage systems containing highly mobile genetic elements (threatening the end of the antibiotic era), and the scene is set for the perfect storm.There is an urgent need for the re-evaluation of the periphery of the water system and drainage systems. Consequently, in this article we examine the requirement and placement of hand wash stations (HWSs), design of showers, kitchens and the dirty utility with respect to water services. Lastly, we discuss the provision of safe water to high-risk patient groups. The purpose of this article is to stimulate debate and provide infection control and design teams with support in deviating from the outdated existing guidance and to challenge conventional thinking until new advice is forthcoming.
  • Prevalence of Clostridioides difficile infection in Central India: a prospective observational cohort study

    Ambalkar, Shrikant (GUT, 2021)
    ntroduction The true burden of Clostridioides difficile infection (CDI) in India remains poorly understood. Prolifigate, unregulated antibiotic use and inappropriate prescribing suggest that CDI could be widespread in India. Our aim was to establish and compare baselines rates of CDI in both in-and outpatient settings in Nagpur city district and rural Melghat, Central India. Methods We recruited adult participants aged ≥18 years of age who could provide written or thumb-print informed consent. A diagnosis of diarrhoea was defined as 3 or more loose stools in a 24-hour period. Immunosuppression was defined as those on prednisolone (>5mg/day), immunomodulators or biologics. Baseline characteristics were also collected and included: demographics, symptomatology, antibiotics exposure, duration of diarrhoea, hospitalisation status at recruitment, and duration, BMI, animal exposure, housing conditions, toilet access, and seasonality. All diarrhoeal samples were tested for CDI using the C. DIFF QUIK CHEK COMPLETE-enzyme immunoassay in accordance with the manufacturers’ instructions. Results C. difficile testing was performed on 1223 patients with acute diarrhoea. A total of 36 patients (2.9%) tested positive for both GDH antigen and toxin expression. A higher% of urban inpatient diarrheal samples tested positive for toxigenic C. difficile (26 cases; 8%) compared to that seen for urban outpatients (9 cases; 3%) and the rural diarrhoeal group (1 outpatient case). Of those testing positive for toxigenic C. difficile, 63.9% were immunosuppressed and almost all (94.4%) were on antibiotics at the time of recruitment. The majority of the toxigenic CDI cases were detected during the monsoon season, lived in very good or good housing conditions, had access to good toilet facilities and reported no co-habitation with animals. Non-toxigenic C. difficile was detected in 6.2%, 4.8%, and 0.5% in the urban inpatient, urban outpatient, and rural populations tested, respectively. Conclusions Toxigenic C. difficile is an important but neglected aetiologic cause of infective diarrhoea in Central India. The higher prevalence within the urban inpatient setting likely reflects greater exposure to antibiotics and hospitalisation. Our findings underscore the need to enhance awareness of and testing of patients with diarrhoea in India, particularly in high-risk individuals with recent or ongoing antibiotic exposure or hospitalisation.
  • Multiplex PCR for determining aetiology of infectious diarrhoea in rural and urban central Indian populations

    Ambalkar, Shrikant (Gut, 2021)
    Introduction Infectious diarrhoea is a major cause of morbidity and mortality in Central India. There is an urgent unmet need to implement rapid point-of-care tests to deliver effective and targeted treatment plans. The aim of this exploratory study was to assess the performance of the FilmArray Gastrointestinal Panel for the detection of enteric pathogens directly from stool specimens collected from diarrhoeal and non-diarrhoeal control populations in Central India. Methods Faecal samples were collected from participants with and without acute diarrhoea presenting to an inpatient or outpatient setting in Nagpur city district and rural Melghat. Each stool sample was stored at 4°C and preserved in Cary-Blair enteric transport medium for multiplex PCR using the FilmArray GI Panel according to the manufacturer’s instructions. This panel allows for the simultaneous detection of 22 common diarrhoeal agents, including bacteria, viruses and protozoa. Baseline characteristics were also recorded and included: demographics, symptomatology, antibiotics exposure, duration of diarrhoea, hospitalisation status at recruitment, and duration, BMI, animal exposure, housing conditions, toilet access, and seasonality. Results 179 participants provided stool samples for analysis on the FilmArray GI Panel. 70 and 109 participants were from rural Melghat and Nagpur urban district, respectively. Of these, 138 were from mainly non-hospitalised participants with acute diarrhoea from urban (n=89) and rural areas (n=49). In the urban cohort, 81% (88/109) of all diarrhoeal and non-diarrhoeal samples tested positive for one (27%) or more (54%) pathogens. In the rural cohort, a striking 97% (68/70) of samples yielded positivity to one (14%) or multiple organisms (83%). The most prevalent pathogen detected in both the diarrhoeal and control cohorts was Enterohaemorrhagic E. coli (51% vs 59%, respectively). However, other pathotypes of diarrhoeagenic E. coli were highly prevalent in both cohorts, including ETEC, EPEC, Shigella/EIEC, and STEC. A higher proportion of diarrhoeal samples tested positive to Campylobacter (12%) compared to the non-diarrhoeal control group (5%). Unlike the diarrhoeal samples, no control samples yielded positivity to Vibrio cholerae, Cyclospora cayetanensis, Astrovirus, Rotavirus A or Sapovirus Conclusions Detection of high levels of polymicrobial enteric infections are prevalent in Central Indian symptomatic and asymptomatic populations. E. coli pathotypes predominate in both urban and rural settings. Further studies are required to understand the clinical significance of these mixed infections, as well as how best to manage them.
  • Water springing to life the fungal desert

    Weinbren, Michael (2021-05)
    Immunosuppressed patients are at increased risk of developing hospital-acquired fungal infections. The risk of fungal infection from construction is well established, but water ingress also presents a risk if it is not dealt with promptly. This article describes four such scenarios and the learning points from each. Water ingress may go under-reported and, as such, may be an underestimated source of fungal healthcare-associated infections.
  • Metagenomics reveals impact of geography and acute diarrheal disease on the Central Indian human gut microbiome.

    Ambalkar, Shrikant (2020-05)
    Background: The Central Indian gut microbiome remains grossly understudied. Herein, we sought to investigate the burden of antimicrobial resistance and diarrheal diseases, particularly Clostridioides difficile , in rural-agricultural and urban populations in Central India, where there is widespread unregulated antibiotic use. We utilized shotgun metagenomics to comprehensively characterize the bacterial and viral fractions of the gut microbiome and their encoded functions in 105 participants. Results: We observed distinct rural-urban differences in bacterial and viral populations, with geography exhibiting a greater influence than diarrheal status. Clostridioides difficile disease was more commonly observed in urban subjects, and their microbiomes were enriched in metabolic pathways relating to the metabolism of industrial compounds and genes encoding resistance to 3 rd generation cephalosporins and carbapenems. By linking phages present in the microbiome to their bacterial hosts through CRISPR spacers, phage variation could be directly related to shifts in bacterial populations, with the auxiliary metabolic potential of rural-associated phages enriched for carbon and amino acid energy metabolism. Conclusions: We report distinct differences in antimicrobial resistance gene profiles, enrichment of metabolic pathways and phage composition between rural and urban populations, as well as a higher burden of Clostridioides difficile disease in the urban population. Our results reveal that geography is the key driver of variation in urban and rural Indian microbiomes, with acute diarrheal disease, including C. difficile disease exerting a lesser impact. Future studies will be required to understand the potential role of dietary, cultural, and genetic factors in contributing to microbiome differences between rural and urban populations.
  • Dissemination of antibiotic resistance and other healthcare waterborne pathogens. The price of poor design, construction, usage and maintenance of modern water/sanitation services.

    Weinbren, Michael (, 2020-03)
    Summary Classical waterborne pathogens (cholera/typhoid) drove the development of safe water and sanitation during the industrial revolution. Whilst effective against these organisms, other bacteria exploited the potential to form biofilm in the narrow pipes of buildings. Legionella was discovered in 1976. Despite evidence dating back to 1967 (including paediatric deaths in Manchester in 1995 from splashes from a sink contaminating parenteral nutrition) it required the deaths of four neonates and the might of the news media in 2011 for the UK medical services to accept waterborne transmission of other opportunistic plumbing premise pathogens (OPPPs). Human nature, a healthcare construction industry largely devoid of interest in water safety, and failures in recognizing transmission are major forces hindering progress in preventing infection/deaths from waterborne infections. The advent of highly resistant Gram-negative bacteria is highlighting further deficiencies in modern drainage systems. These bacteria are not thought to have special adaptations promoting their dispersal but purely attract our attention to the well-trodden routes used by susceptible organisms, which go undetected. The O'Neill report warns of the bleak future without effective antibiotics. This review examines the evidence as to why modern water services/sanitation continue to present a risk to patient safety (and the general public) and suggests that their designs may be flawed if they are to stem the modern equivalent of cholera, the dissemination of antibiotic resistance.
  • Giving the tap the elbow? An observational study.

    Weinbren, Michael (2017-08)
    BACKGROUND: Handwashing is viewed as the most important barrier to cross-infection. Incorrect use of clinical handwash basins may lead to cross-infection either from contaminated water or due to failure to decontaminate hands. Elbow-operated taps used correctly prevent recontamination of hands during operation. Many elbow-operated taps are installed incorrectly, with the handle flush with the back panel, making it difficult to open using the elbow. AIM: To determine the effect of altering the angle of the handle of elbow-operated taps on handwashing technique. METHODS: An observational study was conducted using two rooms; in one the handles of the elbow-operated taps were flush with the inspection panel behind, and in the other they were set at 35°. FINDINGS: Thirty-five staff members washed their hands in both rooms. Hands were used to turn on the taps in 97% of instances. In 57% of washes hands were recontaminated when used to turn the tap off. Only six individuals consistently used their elbows to turn outlets off. Surprisingly, more individuals used their elbows to operate taps whose handles were flush with the inspection panel behind. CONCLUSION: Greater emphasis needs to be placed on correct use of elbow-operated outlets. The decision to use elbow- or sensor-operated outlets is not clear-cut, as each has pros and cons. There is much room for improvement in design and standardization of handwash basins. Given the importance of handwashing it is surprising that these gaps exist.
  • The handwash station: friend or fiend?

    Weinbren, Michael (2018-10)
    Handwashing is a key barrier to cross-infection performed at a handwash station (HWS, an interface between water and drainage systems). Widespread and often uncritical placement/design and use of HWSs is not without attendant risks. Recognition of the associated hazards went unheeded for over 45 years despite warnings in the literature, until the neonatal outbreak of pseudomonas in Belfast in 2012 forced change. Minimizing risk requires a holistic approach beyond the mere testing of water from the outlet of a HWS for the presence of Pseudomonas aeruginosa or other pathogens. Literature reports of outbreaks linked to HWSs outside of neonatal units are over-represented by multi-resistant organisms, and increasingly by carbapenemase-producing organisms. Evidence suggests that a large proportion of waterborne transmissions go undetected. Much could be done to improve current design, use and placement of HWSs, and this is assessed critically in this article.
  • Observation study of water outlet design from a cross-infection/user perspective: time for a radical re-think?

    Weinbren, Michael (2018-11-14)
    Background: Handwashing is a key barrier to cross-infection performed at a handwash station (HWS). Elbow-operated outlets, if used incorrectly (with hands), become highly touched objects, potentially providing a route for cross-infection. Aim: To study how elbow-operated outlets were used by staff in this hospital, whether the correct type of HWS had been installed in the various ward areas according to the Health Building Note (HBN) 00-10 Part C: Sanitary Assemblies (hands-free outlets in clinical, food preparation and laboratory areas), and factors impinging on design/setup which may affect compliance with correct use. Methods: Observation of outlet use was performed by mounting a video camera above four HWSs. Review of suitability of outlet was conducted by two of the authors by visiting ward areas and assessing compliance against HBN recommendations. Angle of elbow-operated lever setup was measured using a protractor and water temperature in relation to angle of movement of elbow lever was measured using a calibrated thermocouple. Findings: Ninety-two percent of staff used hands to turn on the outlet and 68% used hands to turn the outlet off, potentially re-contaminating their hands. More than 70% of users moved the lever ≤45°. Almost half of elbow levers were set up incorrectly, being flush or within 3.5 cm of the rear panel, making elbow operation extremely difficult. Selection of outlet type according to HBN was most incorrect in the intensive treatment unit but also occurred in the newly built parts of the hospital. Conclusions: Although handwashing is a key barrier to cross-infection, poor selection and incorrect use of outlet undermines its effectiveness. Design and incorrect instalment further compromise the intended means of operation of elbow levers. Of equal concern is that this risk mostly goes unrecognized. There is an opportunity to improve handwashing safety, but it requires engagement across a broad stratum from Government Departments of Health and manufacturers down to the user.
  • Down the drain and back up a drain

    Weinbren, Michael (2019-02-08)
    In this issue the paper by Aranega-Bou et al provides one more piece to the jigsaw of our understanding on drains and spread of organisms [1].
  • Antibiotic Prescription, Organisms and its Resistance Pattern in Patients Admitted to Respiratory ICU with Respiratory Infection in Mysuru.

    Ambalkar, Shrikant (2018-04)
    Aim of Study: Respiratory infections account for significant morbidity, mortality and expenses to patients getting admitted to ICU. Antibiotic resistance is a major worldwide concern in ICU, including India. It is important to know the antibiotic prescribing pattern in ICU, organisms and its resistance pattern as there is sparse data on Indian ICUs. Materials and Methods: We conducted a prospective study from August 2015 to February 2016. All patients getting admitted to RICU with respiratory infection who were treated with antibiotics were included into study. Demographic details, comorbidities, Clinco-pathological score (CPI) on day1 and 2 of admission, duration of ICU admission, number of antibiotics used, antibiotic prescription, antimicrobial resistance pattern of patients were collected using APRISE questionnaire. Results: During study period 352 patients were screened and 303 patients were included into study. Mean age was 56.05±16.37 and 190 (62.70%) were men. Most common diagnosis was Pneumonia (66%). Piperacillin-tazobactam was most common empirical antibiotic used. We found 60% resistance to piperacillin-tazobactam. Acinetobacter baumanii was the most common organism isolated (29.2%) and was highly resistant to Carbapenem (60%). Klebsiella pneumoniae was resistant to Amikacin (45%), piperacillin (55%) and Ceftazidime (50%). Conclusion: Piperacillin-tazobactam was the most common antibiotic prescribed to patients with respiratory infection admitted to ICU. More than half of patients (60%) had resistance to the empirical antibiotic used in our ICU, highlighting the need for antibiogram for each ICU. Thirty six percent of patient had prior antibiotic use and had mainly gram negative organisms with high resistance to commonly used antibiotics.