trimethoprim--sulfamethoxazole-drug-combination and Candidiasis

Infection is the major cause of morbidity and mortality in children receiving anticancer therapy. Children who have severe neutropenia (neutrophil count less than 100/mm3) for longer than 2 weeks should receive oral antibiotic prophylaxis. At present, trimethoprim sulfamethoxazole in combination with either nystatin or amphotericin B is the best regimen for reducing the incidence of serious infections. Trimethoprim sulfamethoxazole is very effective in the prevention of Pneumocystis carinii pneumonitis. Clinicans will have to balance the advantages and disadvantages of prophylaxis in patients who are at risk for P. carinii pneumonitis.

Topics: Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Child; Compliance; Drug Combinations; Humans; Leukemia; Neoplasms; Neutropenia; Nystatin; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Clinical trials often assess therapeutic benefit on the basis of an event such as death or the diagnosis of disease. Usually, there are several additional longitudinal measures of clinical status which are collected to be used in the treatment comparison. This paper proposes a simple non-parametric test which combines a time to event measure and a longitudinal measure so that a substantial treatment difference on either of the measures will reject the null hypothesis. The test is applied on AIDS prophylaxis and paediatric trials.

Topics: Acquired Immunodeficiency Syndrome; Anti-HIV Agents; Anti-Infective Agents; Antifungal Agents; Candidiasis; Child; Child, Preschool; Clinical Trials as Topic; Clotrimazole; Dapsone; Didanosine; Drug Therapy, Combination; Fluconazole; Head; Humans; Longitudinal Studies; Pentamidine; Pneumonia, Pneumocystis; Statistics, Nonparametric; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

To determine the efficacy of long-term prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) for prevention of bacterial infection following renal transplantation, the absorption of TMP-SMZ in transplant patients, the effects of prophylaxis on the microflora, and the cost-benefit of prophylaxis.. One hundred thirty-two adult patients selected to undergo renal transplantation participated in a randomized, double-blind, placebo-controlled trial.. Patients randomized to receive TMP-SMZ experienced fewer hospital days with fever (3.3% versus 7.7%, p less than 0.001) and significantly fewer bacterial infections during the transplant hospitalization after removal of a urethral catheter (0.76 versus 1.88 per 100 days, p less than 0.005) and following discharge from the hospital (0.08 versus 0.30 per 100 days, p less than 0.001). During the transplant hospitalization, a daily dose of 320/1,600 mg was highly effective for prophylaxis whereas 160/800 mg daily gave unexpectedly low blood levels and was effective only for prevention of urinary tract infections after catheter removal. Prophylaxis was most effective in prevention of infections of the urinary tract (24 versus 54, p less than 0.005) and bloodstream (one versus nine, p less than 0.01) and infections caused by enteric gram-negative bacilli (four versus 46, p less than 0.001), enterococci (six versus 22, p = 0.006), or Staphylococcus aureus (one versus nine, p = 0.01). Prophylaxis did not prevent urinary tract infection associated with urethral catheters in the early posttransplant period, but after catheter removal, reduced the risk of urinary tract infection threefold (p less than 0.001). No significant differences in colonization by TMP-SMZ-resistant gram-negative bacilli were identified between the two groups; patients given TMP-SMZ were, paradoxically, less likely to become colonized by candida, probably because of less exposure to antibiotics for treatment of infection. Recipients of prophylaxis did not have a higher rate of infection caused by TMP-SMZ-resistant bacteria or Candida; however, their infections were more likely to be caused by resistant bacteria than infections in patients in the placebo group (62% versus 18%, p less than 0.001).. Prophylaxis with TMP-SMZ, which is well tolerated, significantly reduces the incidence of bacterial infection following renal transplantation, especially infection of the urinary tract and bloodstream, can provide protection against Pneumocystis carinii pneumonia, and is cost-beneficial. Subnormal absorption of TMP-SMZ in the early posttransplant period mandates 320/1,600 mg daily for optimal benefit. Prophylaxis has little discernible effect on the microflora.

Topics: Absorption; Adolescent; Adult; Bacteria; Bacterial Infections; Candidiasis; Clinical Trials as Topic; Cost-Benefit Analysis; Double-Blind Method; Female; Humans; Kidney Transplantation; Male; Middle Aged; Placebos; Prospective Studies; Random Allocation; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Catheterization; Urinary Tract Infections

Ketoconazole or miconazole was randomly administered to 42 and 46 neutropenic patients respectively. Of the total number of stool cultures 12% were positive for yeasts in both groups; 4% of the total number of cultures from other sites (nose, throat, skin) were positive in both groups. Candida albicans was the most common isolate, but other fungal species were also identified. No patient developed fungemia; 5/88 patients developed severe oropharyngeal candidiasis while receiving prophylaxis. Among the 21 autopsies performed, 5 cases of pulmonary aspergillosis and 2 local and 1 disseminated candidiasis were demonstrated in 7 patients. Although there was no placebo group of patients in this study, post-mortem data suggest that miconazole or ketoconazole might reduce the incidence of disseminated candidiases in neutropenic patients.

Topics: Agranulocytosis; Antifungal Agents; Candidiasis; Drug Combinations; Female; Humans; Imidazoles; Ketoconazole; Male; Miconazole; Middle Aged; Mycoses; Neoplasms; Neutropenia; Piperazines; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the risk factors for recurrent urinary tract infections (UTIs) in infants with vesicoureteral reflux (VUR) and whether bacterial pathogen affected breakthrough UTI or not.. We compared children with infantile VUR with recurrent UTI (33 males, 11 females, mean age 3.2 months) and without recurrent UTI (40 males, 7 females, mean age 4.8 months). The following were compared between the 2 groups: sex, timing of UTI episode, bacterial growth on urine culture, degree and bilaterality of the reflux, hydronephrosis, renal scar, and delayed ureteral excretion of refluxed contrast on voiding cystourethrogram (VCUG).. Univariate Cox survival-time regression showed that younger age at first UTI, a non-Escherichia coli strain, bilateral and VUR, high-grade VUR, and hydronephrosis on initial ultrasonography (USG) significantly increased the risks of recurrent UTI (P <.05 each). In multivariate analysis, timing of the UTI episode (P = .015), a non-E. coli strain (P = .003), high grade (P = .012), and bilateral VUR (P = .002) were independently associated with increased risk of recurrent UTI. Non-E. coli strains were identified in 60% and 33% of infants with and without recurrent UTI, respectively.. During the first year of life, the earlier the first UTI then the higher the chance is for recurrent UTIs. Higher grades of reflux, bilateral VUR, and the first infection by a non-E. coli strain all significantly increase the risk of recurrent UTIs.

Topics: Antibiotic Prophylaxis; Candida albicans; Candidiasis; Citrobacter freundii; Enterobacter cloacae; Enterobacteriaceae Infections; Escherichia coli; Female; Fever; Humans; Hydronephrosis; Infant; Klebsiella oxytoca; Klebsiella pneumoniae; Male; Multivariate Analysis; Proportional Hazards Models; Proteus mirabilis; Proteus vulgaris; Recurrence; Risk Factors; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Vesico-Ureteral Reflux

Recent exposure to azoles is an important risk factor for infection with fluconazole-resistant Candida spp., but little is known about the role of antibacterial drug exposure in the emergence of drug-resistant Candida. We did a prospective nationwide surveillance study of candidemia in Israel and analyzed the propensity score-adjusted association between antifungal and antibacterial drug exposure and bloodstream infection with C. glabrata and fluconazole-resistant Candida isolates. Four hundred forty-four episodes of candidemia (450 Candida isolates, 69 [15%] C. glabrata isolates, and 38 [8.5%] fluconazole-resistant isolates) from 18 medical centers in Israel were included. C. glabrata bloodstream infection was strongly associated with recent metronidazole exposure (odds ratio [OR], 3.2; P < 0.001). Infection with a fluconazole-resistant isolate was associated with exposure to carbapenems, trimethoprim-sulfamethoxazole, clindamycin, and colistin (odds ratio, 2.8; P = 0.01). The inclusion of antibacterial drug exposure in a multivariable model significantly enhanced the model's predictive accuracy for fluconazole-resistant Candida bloodstream infection. Our findings may be relevant to the selection of empirical antifungal treatment and broaden the scope of antibiotic-associated collateral damage.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antifungal Agents; Bacteria; Bacterial Infections; Candida glabrata; Candidemia; Candidiasis; Carbapenems; Clindamycin; Coinfection; Colistin; Drug Resistance, Fungal; Female; Fluconazole; Humans; Israel; Microbial Sensitivity Tests; Middle Aged; Odds Ratio; Prospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

A case of post-transplantation pneumonia due to Candida krusei is reported. A 42-year-old man was admitted 28 days after heart transplantation with cough, pleuritic pain and fever. A chest computed tomograph showed multiple alveolar infiltrates bilaterally. He received broad-spectrum antibiotics, fluconazole for oral candidiasis, and cotrimoxazole for possible Pneumocystis carinii. A short-lived period of improvement was followed by respiratory failure. Cultures of bronchial washings grew C. krusei and C. albicans. The infection was documented by histology and culture obtained by transthoracic aspiration. Treatment with amphotericin B was initiated, but the patient died. Histology and culture of a pulmonary specimen, obtained immediately post mortem, further documented the infection with C. krusei.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Candida; Candidiasis; Fatal Outcome; Fluconazole; Heart Transplantation; Humans; Immunocompromised Host; Male; Pneumonia; Trimethoprim, Sulfamethoxazole Drug Combination

The synthesis and biological properties of a novel water-soluble echinocandin-like lipopeptide, FR131535, are described. This compound displayed potent in vitro and in vivo antifungal activities. The hemolytic activity of FR901379 was reduced by replacing the acyl side chain. This compound showed good water-solubility, comparable to the natural product FR901379.

Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Bronchogenic Cyst; Candida albicans; Candidiasis; Disease Models, Animal; Echinocandins; Female; Fungal Proteins; Glucosyltransferases; Hemolysis; Membrane Proteins; Mice; Mice, Nude; Peptides; Peptides, Cyclic; Pneumonia, Pneumocystis; Schizosaccharomyces pombe Proteins; Solubility

Among patients infected with human immunodeficiency virus type 1 (HIV-1), early and widespread use of prophylactic regimens against Pneumocystis carinii is changing the pattern of illnesses related to the acquired immunodeficiency syndrome (AIDS).. We conducted a subcohort analysis of 844 men with AIDS (87 percent of whom have since died) from a prospectively followed cohort of 2592 HIV-1-infected homosexual men.. A total of 138 men received prophylaxis before the diagnosis of AIDS, but 39 (28 percent) nevertheless had P. carinii pneumonia at some time. Only four illnesses occurred more frequently in men who received P. carinii prophylaxis before the onset of AIDS: Mycobacterium avium complex disease, which developed in 33.4 percent, as compared with 17.3 percent of the 706 men who did not receive early prophylaxis; wasting syndrome (18.4 percent vs. 6.4 percent); cytomegalovirus disease (44.9 percent vs. 24.8 percent); and esophageal candidiasis (21.3 percent vs. 12.8 percent). Collectively, these four diseases accounted for the initial AIDS-related illness in 42.7 percent of those who received prophylaxis before the onset of AIDS, as compared with 10.7 percent of those who did not. During the three six-month periods before the diagnosis of AIDS (0 to 6, > 6 to 12, and > 12 to 18 months), the geometric mean CD4+ cell counts were 48, 87, and 147 per cubic millimeter, respectively, in men who received prophylaxis against P. carinii, as compared with 118, 211, and 279 per cubic millimeter in those who did not.. M. avium complex disease, esophageal candidiasis, wasting syndrome, and cytomegalovirus disease are more common in HIV-infected patients who have received prophylaxis against P. carinii than in those who have not. Prophylaxis may delay the first AIDS illness for 6 to 12 months.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Candidiasis; CD4-Positive T-Lymphocytes; Cohort Studies; Cytomegalovirus Infections; Dapsone; Esophageal Diseases; HIV-1; Humans; Leukocyte Count; Male; Mycobacterium avium-intracellulare Infection; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Immune consequences of gastrointestinal colonization of CD-1 and CBA/J mice with Candida albicans in the presence or absence of continuous antibiotic treatment with penicillin-tetracycline or trimethoprimsulfamethoxazole were investigated. Intubation with C. albicans in the absence of antibiotics resulted in the induction of low but detectable delayed-type hypersensitivity (DTH), demonstrable by footpad testing with a C. albicans wall glycoprotein (GP), and in the stimulation of a moderate level of protective immunity, demonstrable by intravenous (i.v.) challenge. DTH to a membrane extract, BEX, could not be detected in such animals. However, animals colonized in the presence of antibiotics and then inoculated cutaneously prior to being tested for DTH or protective immunity developed significantly enhanced levels of DTH to GP and BEX and were protected to an even greater extent than animals colonized in the absence of antibiotics who were not inoculated cutaneously. The priming effect of colonization, particularly with respect to the antigen GP, was also obvious from an enzyme-linked immunosorbent assay for GP-specific antibody with sera of mice surviving the i.v. challenge, in that GP-specific antibody was present in the highest titers in colonized animals that had been inoculated cutaneously prior to i.v. challenge. While the antibiotics promoted higher levels of colonization, as evidenced by stomach and fecal cultures of intubated mice, antibiotic administration was not necessary for the induction of C. albicans-specific responses. Moreover, contrary to reports in the literature, antibiotic administration had no adverse effect on the immune responses measured. Females were innately more resistant than males to i.v. challenge with C. albicans, but each sex was capable of developing protective immunity of equal intensity in response to colonization or immunization by cutaneous challenge.

Topics: Animals; Antibodies, Fungal; Candida albicans; Candidiasis; Disease Models, Animal; Drug Combinations; Enzyme-Linked Immunosorbent Assay; Female; Hypersensitivity, Delayed; Immunity, Cellular; Immunization; Male; Mice; Mice, Inbred CBA; Penicillins; Stomach; Sulfamethoxazole; Tetracycline; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Therapy of opportunistic infection in patients with the acquired immunodeficiency syndrome is frustrating, and there is no convincing evidence that aggressive treatment and/or prophylaxis other than for Pneumocystis infection can significantly prolong life. While much clinical effort is expended on treating sequential life-threatening infections, the overall course is usually progressively downhill. Thus, any real impact on the disease should be aimed at the causative viral agent, because it is destruction of a critical component of the immune system that predisposes to opportunistic infections.

Topics: Acquired Immunodeficiency Syndrome; Adult; Candidiasis; Cryptococcosis; Drug Combinations; Humans; Intestinal Diseases, Parasitic; Male; Mycobacterium Infections; Mycoses; Pneumonia, Pneumocystis; Sulfamethoxazole; Toxoplasmosis; Transfusion Reaction; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Diseases

A man who, only in 1979 and on a few occasions, had homosexual contacts, transmitted AIDS virus HTLV-III in 1980 and 1981 to two previously healthy women who did not belong to any AIDS risk group. One of them now has an early form of AIDS, while the other died of AIDS in its full form and her child, born in 1983, has fairly far progressed early symptoms of AIDS. Serum antibodies against HTLV-III were demonstrated in all four subjects.

Topics: Acquired Immunodeficiency Syndrome; Adult; Bone Marrow Examination; Bronchi; Candidiasis; Cerebral Infarction; Child, Preschool; Coitus; Demyelinating Diseases; Drug Combinations; Female; Humans; Ketoconazole; Male; Pneumocystis; Pneumonia; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Thirty patients were treated with continuous ambulatory peritoneal dialysis during 313 patients months. 26 episodes of peritonitis defined by a cloudy dialysate with more than 100 cells/mm1 and more than 50 p. cent of polynuclear were observed. The organisms initially responsible were Gram-positive in 11 cases (6 Staphylococcus aureus, 1 Staphylococcus albus, 4 Streptococcus viridans), a gram negative in 3 cases (1 Klebsiella, 1 serratio, one unidentified), a Candida in 2 cases. In 10 cases, the culture was negative, Initial treatment was peritoneal lavage (40 l/day) with in situ antibiotics: in the absence of Candida, the association sulfamethoxazole (SMZ) (80 mg/l) and trimethoprim (TMP) (16 mg/l) was used; when Candida was present amphotericin B (5 mg/l) was used. The association SMZ + TMP led to cure of PT in 17 cases, in 7 +/- 4 days. In 5 cases, this initial treatment was changed at the 48th hour because of initial resistance in one case or secondary resistance of Candida surinfection (2 cases). Candida surinfection occurred later in 2 other cases. For these 6 primary or secondary Candida peritonitis, the catheter was changed within 48 hours. Nevertheless, death occurred in 3 cases and cure was obtained after 51 +/- 11 days in the 3 other cases.. 1) The initial treatment by SMZ + TMP appears quite effective in most cases (73%). 2) The severity and the high incidence of Candida surinfection suggest that its systematic prophylaxis may be appropriate.

Topics: Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Candidiasis; Drug Combinations; Humans; Kidney Failure, Chronic; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination