A systematic review and meta-analysis of the efficacy and safety of N-acetylcysteine in preventing aminoglycoside-induced ototoxicity: implications for the treatment of multidrug-resistant TB.

BACKGROUND: Ototoxicity is a severe side effect of aminoglycoside antibiotics. Aminoglycosides are recommended for the treatment of multidrug-resistant TB (MDR-TB). N-Acetylcysteine (NAC) appears to protect against drug- and noise-induced hearing loss. This review aimed to determine if coadministering NAC with aminoglycoside affected ototoxicity development, and to assess the safety and tolerability of prolonged NAC administration. METHODS: Eligible studies reported on the efficacy of concomitant NAC and aminoglycoside administration for ototoxicity prevention or long-term (≥ 6 weeks) administration of NAC regardless of indication. Pooled estimates were calculated using a fixed-effects model. Heterogeneity was assessed using the I(2) statistic. RESULTS: Three studies reported that NAC reduced ototoxicity in 146 patients with end-stage renal failure receiving aminoglycosides. Pooled relative risk for otoprotection at 4-6 weeks was 0.14 (95% CI 0.05 to 0.45), and the risk difference was -33.3% (95% CI 45.5% to 21.2%). Eighty-three studies (N=9988) described the administration of NAC for >6 weeks. Abdominal pain, nausea and vomiting, diarrhoea and arthralgia were increased 1.4-2.2 times. DISCUSSION: This review provides evidence for the safety and otoprotective effect of NAC when coadministered with aminoglycoside. It represents a strong justification for a clinical trial to investigate the effect of concomitant NAC treatment in patients receiving aminoglycosides as part of MDR-TB treatment.

Unbiased species-level identification of clinical isolates of coagulase-negative Staphylococci: does it change the perspective on Staphylococcus lugdunensis?

Unbiased species-level identification of coagulase-negative staphylococci (CoNS) using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identified Staphylococcus lugdunensis to be a more commonly isolated CoNS in our laboratory than previously observed. It has also highlighted the possibility of vertical transmission.

Recent acquisition of Helicobacter pylori by Baka pygmies.

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors.

A novel mutation in the calcium-sensing receptor gene in an Irish pedigree showing familial hypocalciuric hypercalcemia: a case report.

INTRODUCTION: Familial hypocalciuric hypercalcemia is a rare autosomal dominant disorder characterized by asymptomatic and non-progressive hypercalcemia due to mutations of the calcium-sensing receptor gene. Disorders of calcium metabolism are very common in the elderly, and they can coexist with familial hypocalciuric hypercalcemia in affected families. CASE PRESENTATION: We describe an Irish family with hypercalcemia and hypocalciuria. The proband, an 80-year-old Irish woman, presented with hypercalcemia, relative hypocalciuria, and an elevated parathormone level. She also had chronic kidney disease stage 3 and vitamin D deficiency. Two of her sons were also found to be hypercalcemic and hypocalciuric. DNA sequencing identified a novel missense inactivating mutation in the calcium sensing-receptor gene of the proband and her two hypercalcemic sons. CONCLUSION: Familial hypocalciuric hypercalcemia due to a novel mutation in the calcium-sensing receptor gene was diagnosed in the proband and her two sons. Disorders of calcium metabolism can be multifarious in the elderly. We suggest that testing first degree relatives for calcium levels and DNA sequencing may have a role in the assessment of elderly patients with parathormone-related hypercalcemia.