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Enteric fever is a major cause of morbidity and mortality in tropical areas worldwide. The Indian subcontinent bears the brunt of the disease, both in terms of absolute case numbers and drug-resistant strains. Recent phylogenetic studies suggest that the multidrug-resistant clade H58 originated in India and subsequently expanded through Asia and Africa. In Africa, it caused unrecognised outbreaks in areas previously considered free of the disease. In this study, we discuss the current status of enteric fever in India, the factors preventing its control and its future directions in this rapidly developing nation.

Intracranial echinococcosis is relatively uncommon and usually occurs in the context of echinococcal lesions elsewhere in the body, mostly liver and lung. Multiple intracranial lesions can result from rupture of an initial single intracranial cyst (in cystic echinococcosis) or from dissemination of systemic disease of the lung, liver or heart (cystic and alveolar echinococcosis). The two main subtypes, cystic and alveolar echinococcosis, present differently and have distinct imaging features in the brain. We discuss the presentation, imaging findings and clinical course of three cases (two cystic and one alveolar) of intracranial echinococcal disease in adults.

Background Hypervirulent K. pneumoniae (hvKp) causes severe community acquired infections, predominantly in Asia. Though initially isolated from liver abscesses, they are now prevalent among invasive infections such as bacteraemia. There have been no studies reported till date on the prevalence and characterisation of hvKp in India. The objective of this study is to characterise the hypervirulent strains isolated from bacteraemic patients for determination of various virulence genes and resistance genes and also to investigate the difference between healthcare associated and community acquired hvKp with respect to clinical profile, antibiogram, clinical outcome and molecular epidemiology. Results Seven isolates that were susceptible to all of the first and second line antimicrobials and phenotypically identified by positive string test were included in the study. They were then confirmed genotypically by presence of rmpA and rmpA2 by PCR. Among the study isolates, four were from patients with healthcare associated infections; none were fatal. All patients with community acquired infection possessed chronic liver disease with fatal outcome. Genes encoding for siderophores such as aerobactin, enterobactin, yersiniabactin, allantoin metabolism and iron uptake were identified by whole genome sequencing. Five isolates belonged to K1 capsular type including one K. quasipneumoniae. None belonged to K2 capsular type. Four isolates belonged to the international clone ST23 among which three were health-care associated and possessed increased virulence genes. Two novel sequence types were identified in the study; K. pneumoniae belonging to ST2319 and K. quasipneumoniae belonging to ST2320. Seventh isolate belonged to ST420. Conclusion This is the first report on whole genome analysis of hypervirulent K. pneumoniae from India. The novel sequence types described in this study indicate that these strains are evolving and hvKp is now spread across various clonal types. Studies to monitor the prevalence of hvKp is needed since there is a potential for the community acquired isolates to develop multidrug resistance in hospital environment and may pose a major challenge for clinical management.

Giardia intestinalis is the commonest gastrointestinal protozoal pathogen worldwide, and causes acute and chronic diarrhoea with malabsorption. First-line treatment is with a nitroimidazole, with a reported efficacy rate of 89%. Failure of treatment can occur in patients with hypogammaglobulinaemia or human immunodeficiency virus (HIV), or be due to nitroimidazole-resistant organisms. There is little evidence to guide the clinical management of nitroimidazole-refractory disease. We performed a retrospective audit of nitroimidazole-refractory giardiasis in returned travellers at the Hospital for Tropical Diseases, London between 2011 and 2013. Seventy-three patients with microscopy-proven or PCR-proven giardiasis in whom nitroimidazole treatment had failed were identified, and their management was investigated. In 2008, nitroimidazole treatment failed in 15.1% of patients. This increased to 20.6% in 2011 and to 40.2% in 2013. Patient demographics remained stable during this period, as did routes of referral. Of patients with giardiasis, 39.0% had travelled to India; this rose to 69.9% in patients with nitroimidazole-refractory disease. Of the patients with refractory disease, 44.6% had HIV serological investigations performed and 36.5% had immunoglobulin levels determined. Patients with refractory disease were treated with various agents, including albendazole, nitazoxanide, and mepacrine, alone or in combination. All 20 patients who received a mepacrine-containing regimen were cured. This data shows a worrying increase in refractory disease, predominantly in travellers from India, which is likely to represent increasing nitroimidazole resistance. Improved tools for the diagnosis of resistant G. intestinalis are urgently needed to establish the true prevalence of nitroimidazole-resistant giardiasis, together with clinical trials to establish the most effective second-line agent for empirical treatment regimens.

The incidence of invasive Staphylococcus aureus (SA) infection has increased in the past decade and is associated with poor outcomes and high mortality rates. Of all the virulence factors, Panton-Valentine Leukocidin (PVL) has received the greatest attention. PVL producing SA strains are more likely to produce severe skin and soft tissue infections (SSTIs) and necrotizing pneumonia. This review focuses on the current evidence on PVL-SA virulence, epidemiology, clinical disease and treatment with relevance to healthcare in India.

Colistin has long been a reserve drug used for the treatment of carbapenem resistant Klebsiella pneumoniae. Carbapenem resistance in K. pneumoniae has been increasing and is as high as 44% in India. Although a reserve agent, with rise in rates of resistance to carbapenems, the usage of colistin has increased over the years leading to slow emergence of resistance. Colistin resistance is mainly mediated by the alteration in the LPS of bacterial outer membrane with the addition of L-Ara4-N and PEtN molecules. These alterations are mediated by mutations in several genes involved in lipidA modifications and most commonly mutations in mgrB gene has been reported. Recently there is emergence of plasmid mediated resistance due to mcr-1 and mcr-2 genes which poses a threat for the rapid global spread. This study aims at characterizing eight colistin resistant K. pneumoniae from bacteremia by whole genome sequencing. Eight K. pneumoniae were isolated from blood culture during 2013 and 2014 at the Department of Clinical Microbiology, Christian Medical College, India. Antimicrobial susceptibility testing was performed and minimum inhibitory concentration (MIC) was determined for colistin and polymyxin B by broth-micro dilution method. Whole genome sequencing was performed using Ion Torrent and the genome of all eight isolates was analyzed. The eight isolates were resistant to all the antimicrobials expect tigecycline. MIC of colistin and polymyxin B were ranged from 4 to 1024 μg/ml and 0.5 to 2048 μg/ml respectively. Multiple mutations were observed in the chromosomal genes involved in lipid A modifications. mcr-1 and mcr-2 gene was absent in all the isolates. The most significant were mutations in mgrB gene. Among the eight isolates, four, three and one were belonged to sequence types ST 231, ST14 and ST147 respectively. Seven isolates had blaOXA−48 like, one co-expressed blaNDM−1 and blaOXA−48 like genes leading to carbapenem resistance. Overall, multiple numbers of alterations have been observed. This includes silent mutations, point mutations, insertions and/or deletions. Mutations in mgrB gene is responsible for resistance to colistin in this study. Due to emergence of resistance to reserve drugs, there is a need for combination therapies for carbapenem resistant K. pneumoniae and colistin must be judiciously used.

Carbapenem-resistant Enterobacteriaceae (CRE) are an increasing cause of nosocomial infection in hospitalized children worldwide. Few studies have investigated risk factors for mortality in children with CRE bloodstream infection (BSI). Data are particularly scarce in areas where NDM and OXA carbapenemases predominate. Here, we investigate mortality rates, clinical and microbiologic risk factors for mortality in 50 pediatric patients with CRE BSI in India.Children younger than 17 years old with meropenem-resistant Klebsiella pneumoniae or Escherichia coli isolated from blood culture in 2014 and 2015 were identified from laboratory records. Clinical records were systematically reviewed for each child to establish mortality at 30 days and clinical details. Bacterial isolates were subjected to meropenem E test and multiplex polymerase chain reaction to determine carbapenemase gene. Data were analyzed to establish clinical and bacterial risk factors for mortality.All CRE BSI were hospital-acquired or associated with healthcare. A total of 84% of children had an underlying comorbidity and 46% had a malignancy. K. pneumoniae was the most common bacteria isolated; NDM was the most common carbapenemase gene detected. The mortality rate was 52%. Significant risk factors for mortality included intensive care admission, intubation, inotropic support and respiratory source. Failure to clear bacteremia and a minimum inhibitory concentration8 mg/L for the isolate was associated with a statistically significant increase in mortality. Mortality rates were significantly lower when two or more effective drugs were used in combination.CRE BSI affects children with multiple comorbidities and repeated admissions to hospital. The mortality rate is high; combination therapy may be beneficial.

Hypervirulent Klebsiella pneumoniae strains have been increasingly reported worldwide, and there is emergence of carbapenem resistance among them. Here, we report the genome sequences of three carbapenem-resistant hypervirulent K. pneumoniae isolates isolated from bacteremic patients at a tertiary-care center in South India.

Colistin has long been a reserve drug used for the treatment of carbapenem resistant Klebsiella pneumoniae. Carbapenem resistance in K. pneumoniae has been increasing and is as high as 44% in India. Although a reserve agent, with rise in rates of resistance to carbapenems, the usage of colistin has increased over the years leading to slow emergence of resistance. Colistin resistance is mainly mediated by the alteration in the LPS of bacterial outer membrane with the addition of L-Ara4-N and PEtN molecules. These alterations are mediated by mutations in several genes involved in lipidA modifications and most commonly mutations in mgrB gene has been reported. Recently there is emergence of plasmid mediated resistance due to mcr-1 and mcr-2 genes which poses a threat for the rapid global spread. This study aims at characterizing eight colistin resistant K. pneumoniae from bacteremia by whole genome sequencing. Eight K. pneumoniae were isolated from blood culture during 2013 and 2014 at the Department of Clinical Microbiology, Christian Medical College, India. Antimicrobial susceptibility testing was performed and minimum inhibitory concentration (MIC) was determined for colistin and polymyxin B by broth-micro dilution method. Whole genome sequencing was performed using Ion Torrent and the genome of all eight isolates was analyzed. The eight isolates were resistant to all the antimicrobials expect tigecycline. MIC of colistin and polymyxin B were ranged from 4 to 1024 μg/ml and 0.5 to 2048 μg/ml respectively. Multiple mutations were observed in the chromosomal genes involved in lipid A modifications. mcr-1 and mcr-2 gene was absent in all the isolates. The most significant were mutations in mgrB gene. Among the eight isolates, four, three and one were belonged to sequence types ST 231, ST14 and ST147 respectively. Seven isolates had blaOXA−48 like, one co-expressed blaNDM−1 and blaOXA−48 like genes leading to carbapenem resistance. Overall, multiple numbers of alterations have been observed. This includes silent mutations, point mutations, insertions and/or deletions. Mutations in mgrB gene is responsible for resistance to colistin in this study. Due to emergence of resistance to reserve drugs, there is a need for combination therapies for carbapenem resistant K. pneumoniae and colistin must be judiciously used.

Carbapenem-resistant organisms are increasingly common worldwide, particularly in India and are associated with high mortality rates especially in patients with severe infection such as bacteremia. Existing drugs such as carbapenems and polymyxins have a number of disadvantages, but remain the mainstay of treatment. The tetracycline class of antibiotics was first produced in the 1940s. Minocycline, tetracycline derivative, although licensed for treatment of wide range of infections, has not been considered for treatment of multidrug-resistant organisms until recently and needs further in vivo studies. Tigecycline, a derivative of minocycline, although with certain disadvantages, has been frequently used in the treatment of carbapenem-resistant organisms. In this article, we review the properties of minocycline and tigecycline, the common mechanisms of resistance, and assess their role in the management of carbapenem-resistant organisms.