Coinfections of Two Strains of NDM-1- and OXA-232-Coproducing Klebsiella pneumoniae in a Kidney Transplant Patient.

We report here a fatal case of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in a renal transplant patient without a travel history in the prior year, from whom 2 genetically different CRKP (sequence type 14 [ST14] and ST2497) strains carrying the same plasmids and antimicrobial resistance genes, including blaNDM-1, blaOXA-232, blaCTX-M-15, armA, and tet(D), were isolated from blood and the abdominal cavity. The isolates were susceptible to colistin, tigecycline, eravacycline, and cefiderocol, which was used to treat the CRKP in combination with ceftazidime-avibactam and polymyxin B and resulted in bacterial clearance. Despite the aggressive treatment, the patient died of ischemic colitis and multiorgan failure.

Prolonged infectiousness of tuberculosis patients in a directly observed therapy short-course program with standardized therapy.

BACKGROUND: Effective tuberculosis control is compromised by a lack of clarity about the timeframe of viable Mycobacterium tuberculosis shedding after treatment initiation under programmatic conditions. This study quantifies time to conversion from smear and culture positivity to negativity in unselected tuberculosis patients receiving standardized therapy in a directly observed therapy short-course (DOTS) program. METHODS: Longitudinal cohort study following up 93 adults initiating tuberculosis therapy in Lima, Peru. Baseline culture and drug susceptibility tests (DSTs) were performed using the MBBacT, proportion, and microscopic observation drug susceptibility (MODS) methods. Smear microscopy and MODS liquid culture were performed at baseline and weekly for 4 weeks then every other week for 26 weeks. RESULTS: Median conversion time from culture positivity to culture negativity of 38.5 days was unaffected by baseline smear status. Patients with fully susceptible tuberculosis had a median time to culture conversion of 37 days; 10% remained culture positive at day 60. Delayed culture conversion was associated with multidrug resistance, regardless of DST method used; non-multidrug resistance as defined by the proportion method and MODS (but not MBBacT) was also associated with delay. Persistent day 60 smear positivity yielded positive and negative predictive values of 67% and 92%, respectively, for detecting multidrug resistance. CONCLUSIONS: Smear and culture conversion in treated tuberculosis patients takes longer than is conventionally believed, even with fully susceptible disease, and must be accounted for in tuberculosis treatment and prevention programs. Persistent day 60 smear positivity is a poor predictor of multidrug resistance. The industrialized-world convention of universal baseline DST for tuberculosis patients should become the standard of care in multidrug resistance-affected resource-limited settings.

Haemophilus influenzae type b conjugate vaccines: considerations for vaccination schedules and implications for developing countries.

Prior to widespread vaccination, Haemophilus influenzae type b was a leading cause of severe childhood bacterial infection, including meningitis, worldwide. Over the last decade the world has taken great strides towards controlling Hib disease through routine use of conjugate vaccines in developed and developing countries. Currently there is no consensus on the appropriate schedule by which to use Hib vaccine. Vaccination schedules around the world vary greatly, particularly between high and low income countries. Questions remain as to the most effective and efficient schedule of primary doses, the need for a booster dose, and the implications of using combination vaccines. Here, we present a synthesis of data supporting various Hib vaccine schedules, with a focus on the implications for developing countries.

Group B streptococcal meningitis in infants beyond the neonatal period.

OBJECTIVES: To describe the clinico-bacteriological profile, and early outcomes of infants diagnosed with Group B streptococcus (GBS) meningitis. METHODS: This was a retrospective review of infants (aged 1 mo to 2 y) diagnosed with GBS meningitis in a tertiary care hospital in New Delhi from October 2010 through January 2012. The clinico-bacteriological data and early outcomes of infants with suspected bacterial meningitis and a positive CSF latex agglutination test for GBS were studied. The CSF samples were subjected to PCR for broad spectrum 16s ribosomal DNA and the GBS species specific gene, the scpB. RESULTS: Twenty seven patients (13 boys, and 14 girls) were diagnosed with GBS meningitis during the study period. Broad spectrum 16s ribosomal DNA PCR was performed on 18 of the 27 CSF samples. Sixteen were positive. All these 16 were also positive for the species specific scpB gene. The median duration of hospital stay was 7 d (range 1-72 d). Nine patients died. One patient each developed ventriculitis, optic atrophy and hydrocephalus. Overall, 12 patients had a complete recovery at discharge. CONCLUSIONS: GBS must be considered in the etiology of bacterial meningitis in Indian infants.

Efficacy of zinc given as an adjunct in the treatment of severe and very severe pneumonia in hospitalized children 2-24 mo of age: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Pneumonia is a leading cause of death; in India, an estimated 370,000 children die of pneumonia each year. Zinc has multiple influences on the immune response to infections. Zinc supplementation has been shown to prevent diarrhea and pneumonia in children. However, zinc's therapeutic effect on respiratory infections is less clear. OBJECTIVE: We evaluated the role of zinc as an adjunct to antibiotics in the treatment of children hospitalized for severe or very severe pneumonia. DESIGN: In this randomized, double-blind, placebo-controlled trial, we enrolled 550 children aged 2-24 mo with severe or very severe pneumonia. Within each hospital and pneumonia-severity stratum, children were randomly assigned to receive zinc (20 mg elemental zinc/d) or a placebo in addition to antibiotics and supportive care. RESULTS: The time to recovery from severe or very severe pneumonia was similar in both groups (HR: 0.98; 95% CI: 0.82, 1.17). In the stratified analysis, zinc was shown to be efficacious in reducing the time to recovery in children with very severe pneumonia (HR: 1.52; 95% CI: 1.03, 2.23); however, the effect was no longer statistically significant after adjustment for differences in severely underweight children in the 2 groups. CONCLUSIONS: This study showed no overall benefit of the addition of zinc to antibiotics in reducing the time to recovery from pneumonia but showed a possible benefit of zinc supplementation in a subgroup of children with very severe pneumonia. Additional research is needed in specific subgroups such as children with very severe pneumonia. This trial was registered at http://www.controlled-trials.com as ISRCTN48954234.

The worldwide impact of the seven-valent pneumococcal conjugate vaccine.

BACKGROUND: Pneumococcal conjugate vaccines (PCV) are emerging as one of the most promising means to prevent pediatric disease. The 7-valent PCV (PCV-7) has been extensively evaluated in clinical trials, and recent evidence from the introduction of PCV-7 through national immunization programs has demonstrated impact on pneumococcal disease. METHODS: Clinical trials have shown PCV-7 to be effective against the more severe forms of pneumococcal infections: pneumonia and invasive pneumococcal disease (IPD), as well as overall child mortality. A review shows the tremendous impact PCV-7 has had to date, and the potential further benefits of the emerging multi-valent vaccines. RESULTS: Since its introduction, the PCV-7 has substantially reduced the incidence of IPD, hospital admissions due to pneumonia and acute otitis media in numerous, mostly high income, low-disease burden countries. The reductions in IPD and pneumonia have also been observed among unvaccinated age groups in countries with routine use of PCV-7, demonstrating that PCV-7 provides herd immunity. Some settings observed an increase in rate of nonvaccine serotype IPD, yet rates of overall and vaccine-serotype IPD show marked reductions post-PCV-7 introduction. Limited data are available on the impact of PCV-7 in lower income countries. The available data from efficacy trials from The Gambia and South Africa suggest that PCV-7 will have substantial impact on reducing pneumococcal disease. CONCLUSION: PCV-7 has shown dramatic reduction in disease and mortality rates in the countries in which it has been introduced. The newly introduced 10-valent and 13-valent pneumococcal vaccines are expected to have substantial disease impact, but monitoring is essential to determine their true impact and sustain further introduction of pneumococcal conjugate vaccines.