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Biomedical subjects

Tom M Chiller

Publications and source records attributed to Tom M Chiller.

7 recordsLinked to original sources

Increase in nalidixic acid resistance among non-Typhi Salmonella enterica isolates in the United States from 1996 to 2003.

Fluoroquinolones commonly are used to treat adult Salmonella infections. Fluoroquinolone treatment has failed for persons infected with nalidixic acid-resistant Salmonella. From 1996 to 2003, state public health laboratories forwarded 12,252 non-Typhi Salmonella enterica isolates to the Centers for Disease Control and Prevention for antimicrobial susceptibility testing; 203 (1.6%) of the isolates were nalidixic acid resistant, and 14 (7%) of those were ciprofloxacin resistant. Resistance to nalidixic acid significantly increased from 0.4% in 1996 to 2.3% in 2003. All ciprofloxacin-resistant isolates had at least one point mutation in the quinolone resistance determining region (QRDR) of gyrA and did not harbor qnr or have point mutations in the QRDR of gyrB, parC, or parE. Continued surveillance of antimicrobial resistance among non-Typhi S. enterica isolates is needed to mitigate the increasing prevalence of nalidixic acid resistance.

Anti-Bacterial Agents↗

Plasmid-mediated quinolone resistance in non-Typhi serotypes of Salmonella enterica.

BACKGROUND: Serious infections with Salmonella species are often treated with fluoroquinolones or extended-spectrum beta-lactams. Increasingly recognized in Enterobacteriaceae, plasmid-mediated quinolone resistance is encoded by qnr genes. Here, we report the presence of qnr variants in human isolates of non-Typhi serotypes of Salmonella enterica (hereafter referred to as non-Typhi Salmonella) from the United States National Antimicrobial Resistance Monitoring System for Enteric Bacteria. METHODS: All non-Typhi Salmonella specimens from the United States National Antimicrobial Resistance Monitoring System for Enteric Bacteria collected from 1996 to 2003 with ciprofloxacin minimum inhibitory concentrations > or = 0.06 microg/mL (233 specimens) and a subset with minimum inhibitory concentrations < or = 0.03 microg/mL (102 specimens) were screened for all known qnr genes (A, B, and S) by polymerase chain reaction. For isolates with positive results, qnr and quinolone resistance-determining region sequences were determined. Plasmids containing qnr genes were characterized by conjugation or transformation. RESULTS: Conjugative plasmids harboring qnrB variants were detected in 7 Salmonella enterica serotype Berta isolates and 1 Salmonella enterica serotype Mbandaka isolate. The S. Mbandaka plasmid also had an extended-spectrum beta -lactamase. Variants of qnrS on nonconjugative plasmids were detected in isolates of Salmonella enterica serotype Anatum and Salmonella enterica serotype Bovismorbificans. CONCLUSIONS: Plasmid-mediated quinolone resistance appears to be widely distributed, though it is still uncommon in non-Typhi Salmonella isolates from the United States, including strains that are quinolone susceptible by the criteria of the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards). The presence of this gene in non-Typhi Salmonella that causes infection in humans suggests potential for spread through the food supply, which is a public health concern.

Adult↗

Reducing diarrhoea in Guatemalan children: randomized controlled trial of flocculant-disinfectant for drinking-water.

OBJECTIVE: To examine the effect of a new point-of-use treatment for drinking-water, a commercially developed flocculant-disinfectant, on the prevalence of diarrhoea in children. METHODS: We conducted a randomized controlled trial among 514 rural Guatemalan households, divided into 42 neighbourhood clusters, for 13 weeks, from 4 November 2002 through 31 January 2003. Clusters assigned to water treatment with the flocculant-disinfectant were compared with those using their usual water-handling practices. The longitudinal prevalence of diarrhoea was calculated as the proportion of total days with diarrhoea divided by the total number of days of observation. The prevalence of diarrhoea was compared using the Wilcoxon rank-sum test. FINDINGS: The 1702 people in households receiving the disinfectant had a prevalence of diarrhoea that was 40% lower than that among the 1699 people using standard water-handling practices (0.9% versus 1.5%; P = 0.001). In households using the flocculant-disinfectant, children < 1 year of age had a 39% lower prevalence of diarrhoea than those in households using their standard practices (3.7% versus 6.0%; P = 0.005). CONCLUSION: In settings where families rarely treat drinking-water, we introduced a novel flocculant-disinfectant that reduced the longitudinal prevalence of diarrhoea, especially among children aged < 1 year, among whom diarrhoea has been strongly associated with mortality. Successful introduction and use of this product could contribute to preventing diarrhoeal disease globally.

Adolescent↗

Coccidioidomycosis.

Coccidioides, a fungus, is endemic to specific parts of the Western Hemisphere. This article examines the prevalence, pathogenesis and host defense, clinical manifestations, diagnosis, and treatment of coccidioidomycosis.

AIDS-Related Opportunistic Infections↗

Efficacy of amphotericin B or itraconazole in a murine model of central nervous system Aspergillus infection.

Given the greater than 90% lethality of clinical central nervous system (CNS) aspergillosis despite current therapies, there is a need for an animal model to study therapeutic strategies. We previously established a model of CNS aspergillosis by intracerebral infection and report here the results of treatment with the two therapies with the greatest clinical experience, i.e., treatments with amphotericin B (AMB) and itraconazole (ITZ). Mice were given cyclophosphamide to produce pancytopenia. AMB was given intraperitoneally (i.p.; 3 mg/kg of body weight) or intravenously (i.v.; 0.8 mg/kg) once daily. ITZ in cyclodextrin was given by gavage once daily at a dose of 100 mg/kg or twice daily at 50 mg/kg. Treatments were started at day 1 postinfection and given for 10 days. At day 15, survivors were euthanatized. Ninety percent of the mice given no treatment died by day 6, and 100% died by day 10. Mice treated with AMB either i.p. or i.v. had 40% survival. Mice treated with ITZ either once or twice per day had a median survival time of 10 days, compared with 4 days for control animals, but a survival rate of only 10%. AMB and ITZ prolonged survival (P, <0.0001 to <0.05) compared with controls. Brains from surviving mice had CFU of Aspergillus fumigatus. This model can be used to compare newer antifungals and to study combination therapy or immunotherapy to find better therapeutic alternatives.

Amphotericin B↗

Development of a murine model of cerebral aspergillosis.

Central nervous system (CNS) Aspergillus infection has a mortality rate in humans that approaches 95%. Because no animal models are available for studying this infection, we sought to develop a murine model of CNS aspergillosis. Inconsistent data were obtained for nonimmunosuppressed CD-1, C57BL/6, and DBA/2N mice after infection by midline intracranial injection of Aspergillus fumigatus. CD-1 mice given cyclophosphamide to produce immunosuppression had continuous pancytopenia. Dose-finding studies in CD-1 mice showed that infection with 5 x 106 conidia/mouse consistently caused 100% mortality by day 5-8; no mice died before day 3. Histologic examination of samples of brain tissue showed focal abscesses containing Aspergillus hyphae. Fungus burdens in brain were higher than those in other organs, although Aspergillus disseminated to the kidneys and the spleen. The model we established provides an opportunity to study immune responses to and therapeutic options for CNS disease in an immunologically defined, genetically manipulable, and inexpensive species.

Animals↗