Objectives To review evidence supporting use of fluoroquinolones as first line agents over other antibiotics for treating typhoid and paratyphoid fever (enteric fever)

Chalwe, Victor

Chilengi, Roma

Colebunders, Robert

d' Alessandro, Umberto

Dujardin, Jean-Claude

Kasongo, Webster

Kestens, Luc

Moerman, Filip

Mulenga, Modest

Mwananyanda, Lawrence

Van geertruyden, Jean-Pierre

van Overmeir, Chantal

English

PubMed

BACKGROUND: Antimonials are the first drug of choice for the treatment of American tegumentary leishmaniasis (ATL); however, their efficacy is not predictable, and this may be linked to parasite drug resistance. We aimed to characterize the in vitro antimony susceptibility of clinical isolates of Peruvian patients with ATL who were treated with sodium stibogluconate and to correlate this in vitro phenotype with different treatment outcomes. METHODS: Thirty-seven clinical isolates were obtained from patients with known disease and treatment histories. These isolates were typed, and the susceptibility of intracellular amastigotes to pentavalent (SbV) and trivalent (SbIII) antimonials was determined. RESULTS: We observed 29 SbV-resistant isolates among 4 species of subgenus Viannia, most of which exhibited primary resistance; isolates resistant only to SbIII; and 3 combinations of in vitro phenotypes: (1) parasites sensitive to both drugs, (2) parasites resistant to both drugs, and (3) parasites resistant to SbV only (the majority of isolates fell into this category). There was no correlation between in vitro susceptibility to both antimonials and the clinical outcome of therapy. CONCLUSION: Antimony insensitivity might occur in a stepwise fashion (first to SbV and then to SbIII). Our data question the definition of true parasite resistance to antimonials. Further studies of treatment efficacy should apply standardized protocols and definitions and should also consider host factors

Yardley, V.

Ortuño, N.

Llanos-Cuentas, A.

Chappuis, F.

De Doncker, S.

Ramirez, L.

Croft, S.

Arevalo, J.

Adaui, V.

Bermudez, H.

Decuypere, S.

Dujardin, J. C.

Tropmed Central Antwerp

American tegumentary leishmaniasis: is antimonial treatment outcome related to parasite drug susceptibility?

Yardley, Vanessa

Ortuno, Nimer

Llanos-Cuentas, Alejandro

Chappuis, Francois

Doncker, Simonne De

Ramirez, Luis

Croft, Simon

Arevalo, Jorge

Adaui, Vanessa

Bermudez, Hernan

Decuypere, Saskia

LSHTM Research Online

American tegumentary leishmaniasis: Is antimonial treatment outcome related to parasite drug susceptibility?

OBJECTIVES: To review evidence supporting use of fluoroquinolones as first line agents over other antibiotics for treating typhoid and paratyphoid fever (enteric fever).



DESIGN: Meta-analysis of randomised controlled trials.



DATA SOURCES: Cochrane Infectious Diseases Group specialised register, CENTRAL (issue 4, 2007), Medline (1966-2007), Embase (1974-2007), LILACS (1982-2007), selected conferences, reference lists, and ongoing trial register (November 2007). Review methods Trials comparing fluoroquinolones with chloramphenicol, cephalosporins, or azithromycin in culture-proven enteric fever were included. Two reviewers extracted data and assessed methodological quality. Odds ratios with 95% confidence intervals were estimated. Trials recruiting over 60% children were analysed separately from trials on adults. Primary outcomes studied were clinical failure, microbiological failure, and relapse.



RESULTS: Twenty trials were included. Trials were small and often of limited methodological quality. Only 10 trials concealed allocation and only three were blinded. In trials on adults, fluoroquinolones were not significantly different from chloramphenicol for clinical failure (594 participants) or microbiological failure (n=378), but reduced clinical relapse (odds ratio 0.14 (95% confidence interval 0.04 to 0.50), n=467, 6 trials). Azithromycin and fluoroquinolones were comparable (n=152, 2 trials). Compared with ceftriaxone, fluoroquinolones reduced clinical failure (0.08 (0.01 to 0.45), n=120, 3 trials) but not microbiological failure or relapse. Compared with cefixime, fluoroquinolones reduced clinical failure (0.05 (0.01 to 0.24), n=238, 2 trials) and relapse (0.18 (0.03 to 0.91), n=218, 2 trials). In trials on children infected with nalidixic acid resistant strains, older fluoroquinolones (ofloxacin) produced more clinical failures than azithromycin (2.67 (1.16 to 6.11), n=125, 1 trial), but there were no differences with newer fluoroquinolones (gatifloxacin, n=285, 1 trial). Fluoroquinolones and cefixime were not significantly different (n=82, 1 trial).



CONCLUSIONS: In adults, fluoroquinolones may be better than chloramphenicol for preventing clinical relapse. Data were limited for other comparisons, particularly for children

Thaver, D

Zaidi, AK

Critchley, J

Azmatullah, A

Madni, SA

Bhutta, ZA

St George's Online Research Archive

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A comparison of fluoroquinolones versus other antibiotics for treating enteric fever: meta-analysis.

D. Thaver

A. K M Zaidi

J. Critchley

A. Azmatullah

S. A. Madni

Z. A Bhutta

Crossref

A comparison of fluoroquinolones versus other antibiotics for treating enteric fever: meta-analysis

BACKGROUND: Human immunodeficiency virus (HIV)-1 infected adults with low CD4 cell count have a higher risk of malaria infection and clinical malaria. We assessed the influence that HIV-1 immune suppression has on the efficacy of antimalarial treatment in adults with uncomplicated malaria. METHODS: This clinical trial included 971 Zambian adults with uncomplicated malaria. Patients were tested for HIV-1, and, if positive, a CD4 cell count was assessed. The primary outcome was recurrent parasitemia corrected by molecular genotyping within 45 days after treatment. RESULTS: HIV-1 infection was detected in 33% (320/971) of adult patients with malaria. Treatment failure was not associated with HIV-1 infection (relative risk [RR], 1.12 [95% confidence interval {CI}, 0.82-1.53]; P=.45). HIV-1-infected patients with a CD4 cell count or=300 cells/microL (RR, 2.24 [95% CI, 1.20-4.14]; P=.01). After genotyping, the risk of recrudescence was higher in HIV-1-infected patients with a CD4 cell count or=300 cells/microL or without HIV-1 infection. Trial registered at http://www.clinicaltrials.gov/; reference number NCT00304980

Van Geertruyden, J. P.

Mulenga, M.

Mwananyanda, L.

Chalwe, V.

Moerman, F.

Chilengi, R.

Kasongo, W.

Van Overmeir, C.

Colebunders, R.

Kestens, L.

D'Alessandro, U.

HIV-1 immune suppression and antimalarial treatment outcome in Zambian adults with uncomplicated malaria

Objectives: To review evidence supporting use of fluoroquinolones as first line agents over other antibiotics for treating typhoid and paratyphoid fever (enteric fever).Design: Meta-analysis of randomised controlled trials. Data sources: Cochrane Infectious Diseases Group specialised register, CENTRAL (issue 4, 2007), Medline (1966-2007), Embase (1974-2007), LILACS (1982-2007), selected conferences, reference lists, and ongoing trial register (November 2007).Review methods: Trials comparing fluoroquinolones with chloramphenicol, cephalosporins, or azithromycin in culture-proven enteric fever were included. Two reviewers extracted data and assessed methodological quality. Odds ratios with 95% confidence intervals were estimated. Trials recruiting over 60% children were analysed separately from trials on adults. Primary outcomes studied were clinical failure, microbiological failure, and relapse.Results: Twenty trials were included. Trials were small and often of limited methodological quality. Only 10 trials concealed allocation and only three were blinded. In trials on adults, fluoroquinolones were not significantly different from chloramphenicol for clinical failure (594 participants) or microbiological failure (n=378), but reduced clinical relapse (odds ratio 0.14 (95% confidence interval 0.04 to 0.50), n=467, 6 trials). Azithromycin and fluoroquinolones were comparable (n=152, 2 trials). Compared with ceftriaxone, fluoroquinolones reduced clinical failure (0.08 (0.01 to 0.45), n=120, 3 trials) but not microbiological failure or relapse. Compared with cefixime, fluoroquinolones reduced clinical failure (0.05 (0.01 to 0.24), n=238, 2 trials) and relapse (0.18 (0.03 to 0.91), n=218, 2 trials). In trials on children infected with nalidixic acid resistant strains, older fluoroquinolones (ofloxacin) produced more clinical failures than azithromycin (2.67 (1.16 to 6.11), n=125, 1 trial), but there were no differences with newer fluoroquinolones (gatifloxacin, n= 285, 1 trial). Fluoroquinolones and cefixime were not significantly different (n=82, 1 trial).Conclusions: In adults, fluoroquinolones may be better than chloramphenicol for preventing clinical relapse. Data were limited for other comparisons, particularly for children

A comparison of fluoroquinolones versus other antibiotics for treating enteric fever: meta-analysis

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