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. 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. 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.

Rationale for review: Enteric fever (EF) caused by Salmonella enterica subspecies enterica serovar Typhi (Salmonella Typhi) and S. Paratyphi (Salmonella Paratyphi) remains an important cause of infectious morbidity and mortality in many low-income countries and, therefore, still poses a major infectious risk for travellers to endemic countries. Main findings: Although the global burden of EF has decreased over the past two decades, prevalence of EF remains high in Asia and Africa, with the highest prevalence reported from the Indian subcontinent. These statistics are mirrored by data on travel-related EF. Widespread and increasing antimicrobial resistance has narrowed treatment options for travel-related EF. Ceftriaxone- and azithromycin-based therapies are commonly used, even with the emergence of extremely drug-resistant typhoid in Pakistan. Preventive measures among locals and travellers include provision of safe food and water and vaccination. Food and water precautions offer limited protection, and the efficacy of Salmonella Typhi vaccines is only moderate signifying the need for travellers to be extra cautious. Recommendations: Improvement in the diagnosis of typhoid with high degree of clinical suspicion, better diagnostic assays, early and accurate detection of resistance, therapy with appropriate drugs, improvements in hygiene and sanitation with provision of safe drinking water in endemic areas and vaccination among travellers as well as in the endemic population are keys to controlling typhoid. While typhoid vaccines are recommended for travellers to high-risk areas, moderate efficacy and inability to protect against Salmonella Paratyphi are limitations to bear in mind. Improved Salmonella Typhi vaccines and vaccines against Salmonella Paratyphi A are required.

Investments in newer diagnostics and antimicrobial treatments are critical to improve management of enteric fever in South Asia, say Christopher Parry and colleagues

Fluoroquinolones are considered the most effective drugs for the treatment of typhoid fever and hence are widely used in the empiric treatment of acute undifferentiated febrile illnesses in India. Recent reports of Salmonella enterica serotype Typhi (S. Typhi) strains with increasing minimum inhibitory concentration (MIC) of ciprofloxacin have raised the fear of potential treatment failures. In this case series of 109 consecutive patients hospitalized with typhoid fever (S. Typhi grown from blood), we documented clinical failure (fever persisting >6 days) in 25 of 46 (54.3%) adults who could be evaluated. Among these, eight (17.4%) had microbiological failure (S. Typhi recovered from blood after 6 days of ciprofloxacin therapy) despite adequate serum ciprofloxacin levels, and all required alternative drugs for treatment. These 8 S. Typhi strains, although susceptible to ciprofloxacin (MIC < 1 microg/mL) (NCCLS 2000), had MICs (median MIC 0.5 microg/mL) that were increased 15-fold compared to S. Typhi strains from patients with typhoid fever seen at our center in 1995 (median MIC 0.032 microg/mL), and were nalidixic acid resistant S. Typhi (NARST) (MIC > or =32 microg/mL). The poor treatment outcomes with ciprofloxacin therapy in patients infected with NARST strains that exhibit an increased ciprofloxacin MIC call for a need to revise the ciprofloxacin breakpoints for S. Typhi.

Objective: 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.