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PubMed2005

Two randomized controlled trials of ceftazidime alone versus ceftazidime in combination with trimethoprim-sulfamethoxazole for the treatment of severe melioidosis.

BACKGROUND: Two antibiotic regimens are used commonly in Thailand for the initial treatment of severe melioidosis: ceftazidime in combination with trimethoprim-sulfamethoxazole (TMP-SMX) and ceftazidime monotherapy. It is not known whether TMP-SMX provides an additional benefit. METHODS: Two prospective, randomized trials that compared these regimens for patients presenting with acute severe melioidosis were started independently at tertiary care hospitals in Ubon Ratchathani and Khon Kaen (in northeastern Thailand), and the results were analyzed together as a prospective, individual-patient data meta-analysis. The primary end point was in-hospital mortality rate. RESULTS: The in-hospital mortality rate among all enrolled patients (n=449) was not significantly different between those randomized to ceftazidime alone (25.1%; 56 of 223 subjects) and those randomized to ceftazidime with TMP-SMX (26.6%; 60 of 226 subjects; odds ratio [OR], 1.08; 95% confidence interval [CI], 0.7-1.7; stratified P=.73). Of the 241 patients with culture-confirmed melioidosis, 51 (21.2%) died. Of these 241 patients, 31 (12.9%) died > or =48 h after the time of study entry. Among patients with melioidosis, there was no difference in death rate between the 2 treatment groups for either all deaths (OR, 0.88; 95% CI, 0.48-1.6; stratified P=.70) or for deaths that occurred > or =48 h after hospital admission (OR, 0.88; 95% CI, 0.41-1.9; stratified P=.73). Conditional logistic regression analysis revealed that bacteremia, respiratory failure, and renal failure were independently associated with death and treatment failure. Drug regimens were not associated with death or treatment failure in this model. CONCLUSION: We conclude that the addition of TMP-SMX to ceftazidime therapy during initial treatment of severe melioidosis does not reduce the acute mortality rate.

Adult↗
PubMed2006

Bacterial pneumonia, HIV therapy, and disease progression among HIV-infected women in the HIV epidemiologic research (HER) study.

BACKGROUND: To determine the rate and predictors of community-acquired bacterial pneumonia and its effect on human immunodeficiency virus (HIV) disease progression in HIV-infected women, we performed a multiple-site, prospective study of HIV-infected women in 4 cities in the United States. METHODS: During the period of 1993-2000, we observed 885 HIV-infected and 425 HIV-uninfected women with a history of injection drug use or high-risk sexual behavior. Participants underwent semiannual interviews, and CD4+ lymphocyte count and viral load were assessed in HIV-infected subjects. Data regarding episodes of bacterial pneumonia were ascertained from medical record reviews. RESULTS: The rate of bacterial pneumonia among 885 HIV-infected women was 8.5 cases per 100 person-years, compared with 0.7 cases per 100 person-years in 425 HIV-uninfected women (P < .001). In analyses limited to follow-up after 1 January 1996, highly active antiretroviral therapy (HAART) and trimethoprim-sulfamethoxazole (TMP-SMX) use were associated with a decreased risk of bacterial pneumonia. Among women who had used TMP-SMX for 12 months, each month of HAART decreased bacterial pneumonia risk by 8% (adjusted hazard ratio [HR(adj)], 0.92; 95% confidence interval [CI], 0.89-0.95). Increments of 50 CD4+ cells/mm3 decreased the risk (HR(adj), 0.88; 95% CI, 0.84-0.93), and smoking doubled the risk (HR(adj), 2.12; 95% CI, 1.26-3.55). Bacterial pneumonia increased mortality risk (HR(adj), 5.02; 95% CI, 2.12-11.87), with adjustment for CD4+ lymphocyte count and duration of HAART and TMP-SMX use. CONCLUSIONS: High rates of bacterial pneumonia persist among HIV-infected women. Although HAART and TMP-SMX treatment decreased the risk, bacterial pneumonia was associated with an accelerated progression to death. Interventions that improve HAART utilization and promote smoking cessation among HIV-infected women are warranted.

Adolescent↗
PubMed1991

Production and characterization of mouse monoclonal antibodies against the transmembrane protein of a human immunodeficiency virus type 2.

We established seven hybridoma clones producing monoclonal antibodies (MAbs) against the envelope transmembrane protein (TMP) of a Ghanian isolate of human immunodeficiency virus type 2 (HIV-2[GH-1]) from mice immunized with the detergent-disrupted purified whole virus. The MAbs were found to react with 35 kilodalton (kD) TMP of the HIV-2[GH-1] virus in a Western blot assay (WB). Two of these MAbs recognized 135 kD proteins in addition to TMP in the lysate of HIV-2[GH-1]-infected cells. Two other MAbs cross-reacted with viral components corresponding to TMPs of HIV-2ROD and SIVMAC isolates in a Western blot. Results of competitive binding assay suggest that there are at least three epitopes on a TMP molecule of the HIV-2[GH-1] isolate. The MAbs did not inhibit syncytium formation between HIV-2[GH-1]-infected MOLT-4 cells and MOLT-4 clone 8 cells, nor virus infection to MOLT-4 clone 8 cells.

Animals↗
PubMed1998

Penicillin-resistant Streptococcus pneumoniae in Colombia: presence of international epidemic clones. Colombian pneumococcal study group.

The global spread of multidrug-resistant Streptococcus pneumoniae clones is well documented in the literature. A study to determine type distribution and antimicrobial susceptibility of invasive pneumococcal isolates from Colombian children under the age of 5 was conducted from 1994 to 1996. Health centers in Santa Fe de Bogota, Medellin, Cali, and other cities collected 409 Streptococcus pneumoniae isolates. Diminished susceptibility to penicillin (DSP) was 15.6%; from these, 11.5% showed intermediate-level resistance (ILR) and 4.1% showed high-level resistance (HLR). Fifty-nine of the DSP isolates were examined by pulse field gel electrophoresis (PFGE). Capsular isolate types were 23F (54%), 14 (24%), 19F (10%), 6B (7%), 9V (3%), and 34 (2%). PFGE analysis revealed that 8 isolates shared the Spanish/USA international clone's characteristic features: PFGE pattern type A, serotype 23F; 87.5% exhibited HLR for penicillin, and all were resistant to trimethoprim/sulfamethoxazole (TMP-SMX), tetracycline, and chloramphenicol. Another 7 isolates showed the French/Spanish international clone's features: PFGE pattern type B, 2 of them being serotype 9V; and 5 type 14; HLR to penicillin was 71%, and all proved resistant to TMP-SMX. A large cluster of 24 isolates (41% of all isolates examined) shared a common PFGE type C, with 14 subtypes; all but one, serotype 34, were serotype 23F and had ILR to penicillin; 58% were resistant to TMP-SMX and 50% to tetracycline, but none presented erythromycin or chloramphenicol resistance. The remaining 20 isolates could be grouped into 12 different PFGE types; ILR was shown in 75% of isolates, 70% were resistant to TMP-SMX and to tetracycline, 15% were resistant to erythromycin, and none were resistant to chloramphenicol. These data suggest that some Colombian isolates are clonally related to two of the well-known international epidemic S. pneumoniae clones.

Colombia↗
PubMed1992

A severe, unusual reaction to trimethoprim-sulfamethoxazole in patients infected with human immunodeficiency virus.

The clinical features of three patients with a life-threatening reaction to trimethoprim-sulfamethoxazole (TMP-SMZ) are presented along with seven other cases from the literature. All patients developed sudden fever and hypotension immediately after the administration of TMP-SMZ; usually this reaction occurred within approximately 2 weeks of completion of a previous course of the drug. All but one patient had a rash. Most patients were hypoxemic and developed diffuse pulmonary infiltrates. All patients responded rapidly to supportive care, while bacterial cultures remained negative. The presence, absence, or character of previous adverse reactions to TMP-SMZ did not predict subsequent severe reactions. Although its mechanism remains unclear, this reaction has features of both IgE-mediated anaphylaxis and cytokine (tumor necrosis factor)-mediated effects. We advise extreme caution, with close observation, when this drug is first readministered to patients who have experienced any TMP-SMZ-associated toxicity within the previous 6-8 weeks.

Adult↗
PubMed1993

Trimethoprim-sulfamethoxazole prophylaxis in granulocytopenic patients with acute leukemia: evaluation of serum antibiotic levels in a randomized, double-blind, placebo-controlled Department of Veterans Affairs Cooperative Study.

Despite widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for prophylaxis in neutropenic patients, questions remain regarding its efficacy, toxicity, the risk of selection of resistant isolates, and the relation of its activity to selective decolonization vs. the attainment of direct inhibitory levels within blood and tissues. We evaluated the effect of TMP-SMZ (160/800 mg orally every 12 hours) in 42 adult granulocytopenic patients (< 100 absolute neutrophils/mm3, mean duration 13.3 days) undergoing chemotherapy for acute leukemia at 11 participating Veterans Administration Medical Centers in a randomized, double-blind, placebo-controlled trial. No significant differences in survival, frequency of bacteremia, overall infections, use of systemic antimicrobial therapy, or adverse effects, including myelosuppression, were observed between patients receiving TMP-SMZ vs. those receiving placebo. All patients acquired trimethoprim-resistant organisms. Concentrations of trimethoprim in serum were significantly lower before febrile episodes than when patients were afebrile. These results suggest that the purported activity of TMP-SMZ may be related to the serum concentration achieved. Moreover, the results highlight the need for additional study of the value of antibiotic prophylaxis in neutropenic patients.

Acute Disease↗
PubMed1995

Preventing Pneumocystis carinii pneumonia in persons infected with human immunodeficiency virus.

Although the incidence of Pneumocystis carinii pneumonia (PCP) among adults infected with human immunodeficiency virus (HIV) has declined, no decline in PCP incidence has been observed among HIV-infected children, and PCP remains the most common serious opportunistic infection among both adults and children in the United States. Some evidence of airborne transmission of P. carinii exists, and some clusters of cases of PCP have been reported; however, data are insufficient to recommend that persons with PCP be separated from immunosuppressed persons as a standard practice. The incidence of PCP can be reduced substantially if persons at risk for PCP are identified and receive adequate chemoprophylaxis. Several drugs and drug combinations are highly effective in preventing PCP. For both adults and children, oral trimethoprim-sulfamethoxazole (TMP-SMZ) is the preferred form of prophylaxis. Adverse effects are commonly associated with the use of TMP-SMZ and in some cases may necessitate withdrawal of the drug until the effects resolve. However, reintroduction at the same dose or at a lower and gradually increasing dose will often permit the continued use of TMP-SMZ. For persons intolerant of TMP-SMZ, dapsone alone and dapsone plus pyrimethamine are effective alternatives. A third alternative is aerosolized pentamidine. Additional drugs of unproven efficacy but of potential use in exceptional cases are available.

AIDS-Related Opportunistic Infections↗
PubMed1996

Endocarditis caused by Stenotrophomonas maltophilia: case report and review.

Stenotrophomonas (Xanthomonas) maltophilia is a rare cause of endocarditis. The extensive resistance of this organism to several antibiotics leaves few options for antimicrobial therapy. In vitro synergism of the combination of trimethoprim-sulfamethoxazole (TMP-SMZ) and ticarcillin/clavulanic acid (TIC/CA) has been demonstrated. To our knowledge, we report the first case of ventriculoatrial cerebrospinal fluid shunt-associated endocarditis due to S. maltophilia. The patient was cured with combination therapy with TMP-SMZ and TIC/CA along with catheter removal. This is also the first report of S. maltophilia endocarditis successfully treated with this antibiotic combination. In a review of the medical literature, only 16 cases of S. maltophilia endocarditis were found. Most patients were intravenous drug users (43.8%) or had either prosthetic heart valves (50%) or an indwelling vascular catheter (18.8%). Although S. maltophilia is usually considered a nosocomial pathogen, about one-half of the cases were community-acquired. Twelve of sixteen patients had left-sided endocarditis. Therapy with a combination of two or more antibiotics was employed in most cases. Seven patients had been given TMP-SMZ therapy, but none had been treated with TIC/CA before. One-half of the patients required cardiac surgery. The overall mortality rate was 33%. Although the optimal antibiotic treatment for S. maltophilia endocarditis remains unknown, the case reported herein reinforces in vitro findings that the combination of TMP-SMZ and TIC/CA may be effective therapy.

Clavulanic Acids↗
PubMedDate not supplied

Use of trimethoprim-sulfamethoxazole for treatment of infections due to Nocardia.

Trimethoprim-sulfamethoxazole (TMP-SMZ) was used for treatment of 34 patients with pulmonary or cutaneous nocardiosis. Of nine patients with primary cutaneous disease, eight had rapid resolution of their infection after short-term therapy and none have relapsed after a follow-up of more than six months. The 25 patients with pulmonary nocardiosis had a good clinical response, but three of five (60%) who completed less than three months of therapy relapsed within four weeks. Of the 10 patients who completed four to six months of therapy, only one (10%) relapsed and this relapse was due to drug resistance. By the method of serial dilution in agar, 96% of 59 isolates of Nocardia had MICs of SMZ of less than 25 micrograms/ml. Fewer than 20% were susceptible to 2.5 micrograms of TMP/ml. Synergy between TMP and SMZ was usually present with ratios of TMP to SMZ of 1:5, 1:1, or 5:1, but was less common at a ratio of 1:20. Disk susceptibility testing was easy to perform and readily separated sensitive from resistant strains. TMP-SMZ is highly effective for the treatment of nocardiosis, but the question of whether it is more effective clinically than a sulfonamide alone remains unanswered.

Adult↗
PubMedDate not supplied

Trimethoprim-sulfamethoxazole in the treatment of malaria, toxoplasmosis, and pediculosis.

The status of trimethoprim-sulfamethoxazole (TMP-SMZ) as a chemotherapeutic agent for malaria, toxoplasmosis, and pediculosis is reviewed. The use of TMP-SMZ may be advocated for the treatment of malaria when concurrent bacterial infections are present or when conventional antimalarial agents are not available. Present evidence suggests that TMP-SMZ is effective in the treatment of toxoplasmosis; however, its role in treatment of this disease requires study. Although TMP-SMZ can eliminate head louse infections, topical insecticidal preparations are the preferred treatment.

Drug Combinations↗
PubMedDate not supplied

Single-dose therapy with trimethoprim-sulfamethoxazole for urinary tract infection in women.

One-hundred-four women with symptoms of lower urinary tract inflammation (dysuria, frequency, and suprapubic tenderness) were randomly assigned to one of two treatment regimens: either a single dose of two double-strength trimethoprim-sulfamethoxazole, (TMP-SMZ) tablets (320 mg of TMP and 1,600 mg of SMZ) or conventional therapy of one double-strength tablet (160 mg of TMP and 800 mg of SMZ) twice a day for 10 days. Eighty-one patients had true bacteriuria; 93% of the infections were eradicated by single-dose therapy and 95% by conventional therapy. Results of an antibody-coated bacteria assay showed no correlation with therapeutic outcome. Clinically important side effects were observed in 4% of patients treated with single-dose therapy and 24% (P less than 0.05) of those treated with conventional therapy. Twenty-three patients had acute urethral syndrome, 14 with and nine without pyuria on initial urinalysis. The 14 with pyuria responded to antimicrobial therapy, whereas those without pyuria did not. This response pattern is consistent with recent data concerning the etiology of acute urethral syndrome. It is concluded that single-dose TMP-SMZ therapy is effective, easily administered, inexpensive, and free from significant side effects, and that it should have broad applicability in the treatment of women with acute, uncomplicated urinary tract infection.

Adolescent↗
PubMedDate not supplied

Parenteral trimethoprim-sulfamethoxazole and carbenicillin as empiric therapy for neutropenic patients with cancer.

A combination of parenteral trimethoprim-sulfamethoxazole and carbenicillin (TMP-SMZ-C) was compared with a gentamicin and carbenicillin combination (G-C) as empiric therapy for the febrile neutropenic patient with cancer in a prospective double-blind trial. Target plasma levels of TMP were achieved easily. When all trials were considered, TMP-SMZ-C was more effective (P less than or equal to 0.045) than G-C. When only proven infections were considered, the two regimens were equally effective. Adverse effects of both regimens were similar. Experience with infections due to individual organisms, particularly Pseudomonas aeruginosa and Staphylococcus aureus, was limited. General recommendations for use of TMP-SMZ-C in this patient population cannot be made until more comprehensive studies are done.

Agranulocytosis↗
PubMed1985

Trimethoprim resistance in multiple genera of Enterobacteriaceae at a U.S. hospital: spread of the type II dihydrofolate reductase gene by a single plasmid.

The percentage of clinical isolates of several species of Enterobacteriaceae, particularly Escherichia coli and Klebsiella pneumoniae, resistant to trimethoprim (TMPR) has increased gradually at the Brigham and Women's Hospital (Boston) in recent years. Thirty-seven of 42 TMPR isolates from six species of gram-negative bacilli conjugally transferred TMP resistance to K12 E. coli. beta-Lactam resistance cotransferred from 21 of the 37 donors, and sulfamethoxazole (SMZ) resistance cotransferred from five of the 37 donors. Plasmids that encoded TMP resistance either alone or with SMZ resistance had a molecular size of approximately 52.5 kilobases, with identical restriction endonuclease-generated "fingerprints." Plasmids encoding beta-lactam-mediated resistance (beta R) were approximately four kilobases larger and had fragment patterns that were identical for all of the TMPR/beta R plasmids tested and had many restriction endonuclease-generated bands in common with TMPR plasmids. Radiolabeled dihydrofolate reductase (DHFR) probes identified the type II DHFR as the determinant of TMP resistance. In contrast with reports from Europe, TMP resistance in multiple species of Enterobacteriaceae was found to be spread in one hospital by a single, stable conjugative plasmid that has a wide host range and encodes the type II DHFR gene.

Conjugation, Genetic↗
PubMed1987

Coordinated multicenter study of norfloxacin versus trimethoprim-sulfamethoxazole treatment of symptomatic urinary tract infections. The Urinary Tract Infection Study Group.

In a coordinated, double-blind multicenter trial among general practitioners, 2,255 consecutive patients with symptoms suggesting urinary tract infection were screened; 886 were randomized to receive 200 mg of norfloxacin (333 patients), 400 mg of norfloxacin (335), or 160 mg/800 mg of trimethoprim-sulfamethoxazole (TMP-SMZ; 218) twice daily for seven days. We analyzed bacteriologic efficacy for 252, 240, and 141 of the patients receiving 200 mg of norfloxacin, 400 mg of norfloxacin, or TMP-SMZ, respectively. The short-term efficacy was 97.5%-98.6%, and the accumulated efficacy was 87.9%-88.8%. In patients with complicated infections and in men, the efficacy for the group receiving 200 mg of norfloxacin was lower than that for the other groups. In patients with recurrent infection, bacterial elimination was greater for those receiving TMP-SMZ. Significantly fewer adverse reactions occurred in patients receiving norfloxacin than in those treated with TMP-SMZ. The 200-mg dosage of norfloxacin seemed to cause fewer side effects than the 400-mg dosage.

Adult↗
PubMed1988

Nasopharyngeal carriage of antibiotic-resistant pneumococci by children in group day care.

We compared rates of antibiotic resistance in strains of Streptococcus pneumoniae recovered from nasopharyngeal secretions of a group of children studied longitudinally in a research day care center between 1978 and 1985 and recovered from usually sterile body fluids of patients at a tertiary care hospital between 1981 and 1985. The prevalence of trimethoprim-sulfamethoxazole (TMP-SMZ) resistance was 11.5% in isolates from the hospital, whereas 30.0% of episodes of nasopharyngeal carriage of S. pneumoniae studied in day care children included TMP-SMZ-resistant isolates. The proportion of episodes of colonization with TMP-SMZ-resistant isolates in the day care study increased from 5.4% before 1981 to 39% between 1981 and 1985. Isolates of S. pneumoniae relatively resistant (MIC greater than or equal to 0.125 micrograms/mL) to penicillin G, amoxicillin, or cefuroxime accounted for 8% of isolates from the hospital and 11.9% of episodes of nasopharyngeal colonization in children in day care. Pneumococci with reduced susceptibility to either TMP-SMZ or a beta-lactam antibiotic were recovered from 68% of 72 children in the day care study.

Amoxicillin↗
PubMed1990

Increase of trimethoprim resistance among Shigella species, 1975-1988: analysis of resistance mechanisms.

Trimethoprim (TMP) resistance among Shigella species isolated from Finnish travelers increased from 3.0% in 1975-1982 to 42.0%-43.8% in 1987-1988. Of the 317 TMP-resistant Shigella isolates identified during 1975-1988, 175 (55%) collected in 1985-1987 and in 1988 were tested further. Almost all (98%) were highly resistant to TMP, suggesting a plasmid-mediated origin. The type I dihydrofolate reductase (DHFR) gene was detected in 85% of the isolates studied. Twenty-three percent of the type I DHFR-positive isolates failed to hybridize with a probe detecting only Tn7-derived sequences, suggesting that the type I DHFR gene may occur independently of transposon Tn7. Four of the five Shigella species isolated from travelers to Sri Lanka hybridized with the probe for type V DHFR gene, implying a local distribution of the type V DHFR gene. The type II and type III DHFR genes were not found among the isolates studied. Only 12% of the TMP-resistant Shigella isolates failed to hybridize with any of the DHFR gene probes used.

DNA Probes↗
PubMed1990

Trimethoprim-sulfamethoxazole prophylaxis in the management of chronic granulomatous disease.

Long-term oral antimicrobial prophylaxis is accepted practice in the management of patients with chronic granulomatous disease (CGD). Reports of adverse outcome with trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis in other patient groups, and the recent occurrence of several severe fungal infections in patients followed at the National Institutes of Health (NIH), prompted a review of the NIH experience to examine the incidence of nonfungal and fungal infections in CGD patients with and without TMP-SMX prophylaxis. Prophylaxis decreased the incidence of nonfungal infections from 7.1 to 2.4 per 100 patient-months in patients with autosomal CGD (P less than .01) and from 15.8 to 6.9 infections per 100 patient-months (P = .06) in X-linked CGD patients. There was no significant change in the incidence of fungal infection in CGD patients on TMP-SMX (1.5-0.3 fungal infections/100 patient-months in autosomal CGD and 1.7-0.2 fungal infections/100 patient-months in X-linked CGD patients). TMP-SMX prophylaxis is indicated for the management of patients with CGD and decreases the incidence of non-fungal infections without increasing the incidence of fungal infections.

Genetic Linkage↗
PubMed1993

Ciprofloxacin and trimethoprim-sulfamethoxazole versus placebo in acute uncomplicated Salmonella enteritis: a double-blind trial.

The role of ciprofloxacin and trimethoprim-sulfamethoxazole (TMP-SMZ) was evaluated in empiric treatment of uncomplicated Salmonella enteritis in a comparative, double-blind trial. Patients were randomized to receive ciprofloxacin (500 mg), TMP-SMZ (160/800 mg), or placebo orally twice daily for 5 days. There were 65 evaluatable patients with acute, uncomplicated, culture-confirmed Salmonella enteritis. Duration of diarrhea, abdominal pain, or vomiting and time to defervescence were not significantly different for patients treated with ciprofloxacin, TMP-SMZ, or placebo; there also were no significant differences with respect to full resolution of symptoms for ciprofloxacin versus placebo (point estimate, 0.2 days; 95% confidence interval [CI], -0.5 to 0.9 days) or for TMP-SMZ versus placebo (point estimate, 0.2 days; 95% CI, -1.0 to 0.6 days). The rate of clearance of salmonellae from stools was not significantly different among the groups.

Acute Disease↗