The Pakistan program for control of acute respiratory tract infections (ARIs) adopted the standard ARI-case-management strategy of the World Health Organization and recommended co-trimoxazole for the management of nonsevere pneumonia. Reports in that country of high in vitro antimicrobial resistance of Streptococcus pneumoniae and Haemophilus influenzae to co-trimoxazole prompted the program to reevaluate its treatment policy. Two community-based studies during 1991-1993 showed in vivo efficacy of co-trimoxazole in 92% and 91% of children with nonsevere pneumonia. A third double-blind trial showed co-trimoxazole and oral amoxicillin to be equally effective in vivo in cases of nonsevere pneumonia, despite high in vitro resistance. Country-wide surveillance from 1991 to 1994 revealed 78.3%-79.9% in vitro resistance to co-trimoxazole among S. pneumoniae isolates and 59.5%-61.0% among H. influenzae isolates. Co-trimoxazole is still recommended by the Pakistan ARI control program. The fact that amoxicillin is three times more expensive and must be administered more frequently is a big impediment to recommending it as a first-line drug for nonsevere pneumonia.
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Medication nonadherence in the treatment of chronic diseases compromises the effectiveness of therapy. Little information is available about the extent of medication adherence or determinants of medication adherence in HIV disease, an issue of increasing importance in this new therapeutic era of combination antiretroviral therapy.
Observational case report.
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To determine the prevalence and clinical manifestations of Cyclospora in Haitians infected with human immunodeficiency virus (HIV) who have diarrhea and to evaluate therapy and prophylaxis.
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This assessment series included 18 patients with a confirmed diagnosis of actinomycetoma, and who had shown a poor response to previous treatments. Patient received a combination therapy of the Welsh regimen (amikacin along with cotrimoxazole) to which rifampicin was added as a third drug. Clinical evaluation included radiology and laboratory investigations.
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The high prevalence of resistance to trimethoprim-sulfamethoxazole and other antimicrobials among Escherichia coli causing acute cystitis in women has led to increased use of alternative antibiotics. One such antibiotic, amoxicillin-clavulanate, has not been well studied.
In a controlled clinical trial based on 30 geriatric patients with recurrent urinary tract infection, 12 out of 17 patients fulfilled a 12-month treatment with sulphamethoxazole/trimethoprim (Bactrim) with continuous sterile urine compared to 1 out of 13 patients treated with nitrofurantoin (p less than 0.05). There was a slight but statistically significant increase in serum creatinine during treatment for 12 months in the sulphamethoxazole/trimethoprim group, but this probably does not reflect any deterioration in kidney function. The remaining laboratory values showed no significant changes whatsoever.
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An intermittent regimen of trimethoprim-sulfamethoxazole was tested in the corticosteroid-treated rat model to learn whether or not administration for 3 consecutive days a week would provide prophylaxis equal to continuous daily doses. Although all of the untreated control animals acquired Pneumocystis carinii pneumonia, none of the animals given either continuous or intermittent trimethoprim-sulfamethoxazole became infected.
Tests for antibiotic resistance were carried out on 198 strains of Salmonella typhi and S. paratyphi A isolated from cases of enteric fevers. Their minimal inhibitory concentrations for streptomycin, chloramphenicol, ampicillin, furazolidine and co-trimoxazole were estimated by plate dilution technique. Four strains of S. typhi and one strain of S. paratyphi A were found to show multiple resistance with a set pattern of resistance to chloramphenicol, streptomycin, sulphonamide, tetracycline and spectinomycin. All the five strains carried R-factors. Three of the resistant S. typhi belonged to Phage type 'O' and one was in Phage type 'A'. The single resistant S. paratyphi A belonged to Phage type '2'.
The study was conducted in the community setting in 14 districts of Madagascar from October 2008 to May 2009. Conventional methods and PCR were used to identify the bacteria; antimicrobial susceptibility was determined using an agar diffusion method for enterobacteriaceae and MICs were measured by an agar dilution method for Campylobacter sp. In addition to the strains isolated during this study, Salmonella sp and Shigella sp isolated at the Pasteur Institute of Madagascar from 2005 to 2009 were included in the analysis to increase the power of the study.
Pneumocystis pneumonia (PCP) is an opportunistic infection that occurs in humans and other mammals with debilitated immune systems. These infections are caused by fungi in the genus Pneumocystis, which are not susceptible to standard antifungal agents. Despite decades of research and drug development, the primary treatment and prophylaxis for PCP remains a combination of trimethoprim (TMP) and sulfamethoxazole (SMX) that targets two enzymes in folic acid biosynthesis, dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), respectively. There is growing evidence of emerging resistance by Pneumocystis jirovecii (the species that infects humans) to TMP-SMX associated with mutations in the targeted enzymes. In the present study, we report the development of an accurate quantitative model to predict changes in the binding affinity of inhibitors (Ki, IC50) to the mutated proteins. The model is based on evolutionary information and amino acid covariance analysis. Predicted changes in binding affinity upon mutations highly correlate with the experimentally measured data. While trained on Pneumocystis jirovecii DHFR/TMP data, the model shows similar or better performance when evaluated on the resistance data for a different inhibitor of PjDFHR, another drug/target pair (PjDHPS/SMX) and another organism (Staphylococcus aureus DHFR/TMP). Therefore, we anticipate that the developed prediction model will be useful in the evaluation of possible resistance of the newly sequenced variants of the pathogen and can be extended to other drug targets and organisms.