Geographical and temporal trends and seasonal relapse in Plasmodium ovale spp. and Plasmodium malariae infections imported to the UK between 1987 and 2015.

BACKGROUND: Plasmodium ovale spp. and P. malariae cause illness in endemic regions and returning travellers. Far less is known about these species than P. falciparum and P. vivax. METHODS: The UK national surveillance data, collected 1987 to 2015, were collated with the International Passenger Survey and climatic data to determine geographical, temporal and seasonal trends of imported P. ovale spp. and P. malariae infection. RESULTS: Of 52,242 notified cases of malaria, 6.04% (3157) were caused by P. ovale spp. and 1.61% (841) by P. malariae; mortality was 0.03% (1) and 0.12% (1), respectively. Almost all travellers acquired infection in West or East Africa. Infection rate per travel episode fell fivefold during the study period. The median latency of P. malariae and P. ovale spp. was 18 and 76 days, respectively; delayed presentation occurred with both species. The latency of P. ovale spp. infection imported from West Africa was significantly shorter in those arriving in the UK during the West African peak malarial season compared to those arriving outside it (44 days vs 94 days, p < 0.0001), implying that relapse synchronises with the period of high malarial transmission. This trend was not seen in P. ovale spp. imported from East Africa nor in P. malariae. CONCLUSION: In West Africa, where malaria transmission is highly seasonal, P. ovale spp. may have evolved to relapse during the malarial high transmission season. This has public health implications. Deaths are very rare, supporting current guidelines emphasising outpatient treatment. However, late presentations do occur.

Diagnosis and management of Panton-Valentine leukocidin toxin associated Staphylococcus aureus infection: an update.

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.

Evolving Rapid Methicillin-resistant Staphylococcus aureus Detection: Cover All the Bases.

The dissemination of methicillin-resistant (MR) Staphylococcus aureus (SA) in community and health-care settings is of great concern and associated with high mortality and morbidity. Rapid detection of MRSA with short turnaround time can minimize the time to initiate appropriate therapy and further promote infection control. Early detection of MRSA directly from clinical samples is complicated by the frequent association of MRSA with methicillin-susceptible SA (MSSA) and coagulase-negative Staphylococcus (CoNS) species. Infection associated with true MRSA or MSSA is differentiated from CoNS, requires target specific primers for the presence of SA and mec A or nuc or fem A gene for confirmation of MR. Recently, livestock-associated MRSA carrying mec C variant complicates the epidemiology of MRSA further. Several commercial rapid molecular kits are available with a different combination of these targets for the detection of MRSA or MSSA. The claimed sensitivity and specificity of the currently available commercial kits is varying, because of the different target combination used for detection of SA and MR.

Minocycline and Tigecycline: What Is Their Role in the Treatment of Carbapenem-Resistant Gram-Negative Organisms?

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.

Clinical and Bacterial Risk Factors for Mortality in Children With Carbapenem-resistant Enterobacteriaceae Bloodstream Infections in India.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 concentration > 8 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. CONCLUSIONS: CRE BSI affects children with multiple comorbidities and repeated admissions to hospital. The mortality rate is high; combination therapy may be beneficial.

Draft Genome Sequences of Three Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae Isolates from Bacteremia.

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.

Molecular Mechanisms of Colistin Resistance in Klebsiella pneumoniae Causing Bacteremia from India-A First Report.

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.