Concomitant Bacteremia in Adults With Severe Falciparum Malaria.

BACKGROUND: Approximately 6% of children hospitalized with severe falciparum malaria in Africa are also bacteremic. It is therefore recommended that all children with severe malaria should receive broad-spectrum antibiotics in addition to parenteral artesunate. Empirical antibiotics are not recommended currently for adults with severe malaria. METHODS: Blood cultures were performed on sequential prospectively studied adult patients with strictly defined severe falciparum malaria admitted to a single referral center in Vietnam between 1991 and 2003. RESULTS: In 845 Vietnamese adults with severe falciparum malaria admission blood cultures were positive in 9 (1.07%: 95% confidence interval [CI], .37-1.76%); Staphylococcus aureus in 2, Streptococcus pyogenes in 1, Salmonella Typhi in 3, Non-typhoid Salmonella in 1, Klebsiella pneumoniae in 1, and Haemophilus influenzae type b in 1. Bacteremic patients presented usually with a combination of jaundice, acute renal failure, and high malaria parasitemia. Four bacteremic patients died compared with 108 (12.9%) of 836 nonbacteremic severe malaria patients (risk ratio, 3.44; 95% CI, 1.62-7.29). In patients with >20% parasitemia the prevalence of concomitant bacteremia was 5.2% (4/76; 95% CI, .2-10.3%) compared with 0.65% (5/769; 0.08-1.2%) in patients with <20% parasitemia, a risk ratio of 8.1 (2.2-29.5). CONCLUSIONS: In contrast to children, the prevalence of concomitant bacteremia in adults with severe malaria is low. Administration of empirical antibiotics, in addition to artesunate, is warranted in the small subgroup of patients with very high parasitemias, emphasizing the importance of quantitative blood smear microscopy assessment, but it is not indicated in most adults with severe falciparum malaria.

A randomized controlled pilot study of artesunate versus triclabendazole for human fascioliasis in central Vietnam.

Human fascioliasis caused by Fasciola hepatica or Fasciola gigantica is an increasing global problem. The mainstay of current treatment is triclabendazole, but resistance in animals has been described, and it is not available in many countries. The antimalarial artesunate has an excellent safety profile, and there is increasing evidence of its efficacy against other parasites both in vitro and in vivo. We performed a study to investigate the usefulness of artesunate in symptomatic human fascioliasis; 100 patients were enrolled. Patients treated with artesunate were significantly more likely to be free of abdominal pain at hospital discharge (50/50 versus 44/50, P = 0.027, relative risk 1.14, 95% confidence interval 1.03-1.26), but the complete response rate at 3 months was lower than for patients treated with triclabendazole (38/50 versus 46/50, P = 0.05, RR 0.83, 95% CI 0.69-0.98, artesunate versus triclabendazole). There may be a role for artesunate in fascioliasis.

Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data.

BACKGROUND: Dexamethasone improves outcome for some patients with bacterial meningitis, but not others. We aimed to identify which patients are most likely to benefit from dexamethasone treatment. METHODS: We did a meta-analysis of individual patient data from the randomised, double-blind, placebo-controlled trials of dexamethasone for bacterial meningitis in patients of all ages for which raw data were available. The pre-determined outcome measures were death at the time of first follow-up, death or severe neurological sequelae at 1 month follow-up, death or any neurological sequelae at first follow-up, and death or severe bilateral hearing loss at first follow-up. Combined odds ratios (ORs) and tests for heterogeneity were calculated using conventional Mantel-Haenszel statistics. We also did exploratory analysis of hearing loss among survivors and other exploratory subgroup analyses by use of logistic regression. FINDINGS: Data from 2029 patients from five trials were included in the analysis (833 [41.0%] aged <15 years). HIV infection was confirmed or likely in 580 (28.6%) patients and bacterial meningitis was confirmed in 1639 (80.8%). Dexamethasone was not associated with a significant reduction in death (270 of 1019 [26.5%] on dexamethasone vs 275 of 1010 [27.2%] on placebo; OR 0.97, 95% CI 0.79-1.19), death or severe neurological sequelae or bilateral severe deafness (42.3%vs 44.3%; 0.92, 0.76-1.11), death or any neurological sequelae or any hearing loss (54.2%vs 57.4%; 0.89, 0.74-1.07), or death or severe bilateral hearing loss (36.4%vs 38.9%; 0.89, 0.73-1.69). However, dexamethasone seemed to reduce hearing loss among survivors (24.1%vs 29.5%; 0.77, 0.60-0.99, p=0.04). Dexamethasone had no effect in any of the prespecified subgroups, including specific causative organisms, pre-dexamethasone antibiotic treatment, HIV status, or age. Pooling of the mortality data with those of all other published trials did not significantly change the results. INTERPRETATION: Adjunctive dexamethasone in the treatment of acute bacterial meningitis does not seem to significantly reduce death or neurological disability. There were no significant treatment effects in any of the prespecified subgroups. The benefit of adjunctive dexamethasone for all or any subgroup of patients with bacterial meningitis thus remains unproven. FUNDING: Wellcome Trust UK.

Antimicrobial drug resistance of Salmonella enterica serovar typhi in asia and molecular mechanism of reduced susceptibility to the fluoroquinolones.

This study describes the pattern and extent of drug resistance in 1,774 strains of Salmonella enterica serovar Typhi isolated across Asia between 1993 and 2005 and characterizes the molecular mechanisms underlying the reduced susceptibilities to fluoroquinolones of these strains. For 1,393 serovar Typhi strains collected in southern Vietnam, the proportion of multidrug resistance has remained high since 1993 (50% in 2004) and there was a dramatic increase in nalidixic acid resistance between 1993 (4%) and 2005 (97%). In a cross-sectional sample of 381 serovar Typhi strains from 8 Asian countries, Bangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, and central Vietnam, collected in 2002 to 2004, various rates of multidrug resistance (16 to 37%) and nalidixic acid resistance (5 to 51%) were found. The eight Asian countries involved in this study are home to approximately 80% of the world's typhoid fever cases. These results document the scale of drug resistance across Asia. The Ser83-->Phe substitution in GyrA was the predominant alteration in serovar Typhi strains from Vietnam (117/127 isolates; 92.1%). No mutations in gyrB, parC, or parE were detected in 55 of these strains. In vitro time-kill experiments showed a reduction in the efficacy of ofloxacin against strains harboring a single-amino-acid substitution at codon 83 or 87 of GyrA; this effect was more marked against a strain with a double substitution. The 8-methoxy fluoroquinolone gatifloxacin showed rapid killing of serovar Typhi harboring both the single- and double-amino-acid substitutions.