Cost-effectiveness analysis of HLA-B*13:01 screening for the prevention of co-trimoxazole-induced severe cutaneous adverse reactions among HIV-infected patients in Thailand.

Studies found a strong association between HLA-B*13:01 allele and co-trimoxazole-induced severe cutaneous adverse reactions (SCARs). Genetic screening before initiation of co-trimoxazole may decrease the incidence of co-trimoxazole-induced SCARs. This study aims to evaluate the cost-effectiveness of HLA-B*13:01 screening before co-trimoxazole initiation in HIV-infected patients in Thailand. A combination of a decision tree model and a Markov model was used to estimate lifetime costs and outcomes of two strategies including 1) HLA-B*13:01 screening before co-trimoxazole initiation and 2) usual practice from a societal perspective. Alternative drugs are not considered because dapsone (the second-line drug) also presents a genetic risk. Input parameters were obtained from literature, government documents, and part of the TREAT Asia HIV Observational Database (TAHOD). One-way sensitivity analyses and probabilistic analyses were performed to determine robustness of the findings. HLA-B*13:01 screening resulted in 0.0061 quality-adjusted life years (QALYs) loss with an additional cost of 370 THB ($11.84). At the cost-effectiveness threshold of 160,000 THB ($5,112.85), the probability of the genetic screening strategy being cost-effective is 9.54%. This analysis demonstrated that HLA-B*13:01 allele screening before initiation of co-trimoxazole among HIV-infected patients is unlikely to be cost-effective in Thailand. Our findings will help policymakers make an evidence-informed decision making.

Antibiotic Prophylaxis for Melioidosis in Patients Receiving Hemodialysis in the Tropics? One Size Does Not Fit All.

Melioidosis has a high case fatality rate and is more common in patients with chronic kidney disease. Some authors recommended trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis for all hemodialysis (HD) patients during the wet season in melioidosis-endemic regions. Historical data were reviewed to determine if TMP/SMX prophylaxis was warranted in the HD population of Far North Queensland, Australia. Between 1997 and 2017, there were 242 culture-confirmed cases of melioidosis in the region, three (1.2%) occurred in HD patients; all survived without intensive care support. During the study period, there were 843 HD patients in the region with 3,024 cumulative patient years of risk. Even assuming 100% efficacy, it would have been necessary to prescribe TMP/SMX for 1,008 patient years to prevent one case of melioidosis. Given the significant additional cost and potentially life-threatening side effects of TMP/SMX therapy, clinicians should review the local epidemiology of melioidosis before the implementation of universal TMP/SMX prophylaxis in their HD population.

Comparing the cost-effectiveness of linezolid to trimethoprim/sulfamethoxazole plus rifampicin for the treatment of methicillin-resistant Staphylococcus aureus infection: a healthcare system perspective.

OBJECTIVE: Few industry-independent studies have been conducted to compare the relative costs and benefits of drugs to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. We performed a stochastic cost-effectiveness analysis comparing two treatment strategies-linezolid versus trimethoprim-sulfamethoxazole plus rifampicin-for the treatment of MRSA infection. METHODS: We used cost and effectiveness data from a previously conducted clinical trial, complementing with other data from published literature, to compare the two regimens from a healthcare system perspective. Effectiveness was expressed in terms of quality-adjusted life-years (QALYs). Several sensitivity analyses were performed using Monte Carlo simulation, to measure the effect of potential parameter changes on the base-case model results, including potential differences related to type of infection and drug toxicity. RESULTS: Treatment of MRSA infection with trimethoprim-sulfamethoxazole plus rifampicin and linezolid were found to cost on average €146 and €2536, and lead to a gain of 0.916 and 0.881 QALYs, respectively. Treatment with trimethoprim-sulfamethoxazole plus rifampicin was found to be more cost-effective than linezolid in the base case and remained dominant over linezolid in most alternative scenarios, including different types of MRSA infection and potential disadvantages in terms of toxicity. With a willingness-to-pay threshold of €0, €50 000 and €200 000 per QALY gained, trimethoprim-sulfamethoxazole plus rifampicin was dominant in 100%, 96% and 85% of model iterations. A 95% discount on the current purchasing price of linezolid would be needed when it goes off-patent for it to represent better value for money compared with trimethoprim-sulfamethoxazole plus rifampicin. CONCLUSIONS: Combined treatment of trimethoprim-sulfamethoxazole plus rifampicin is more cost-effective than linezolid in the treatment of MRSA infection.

Cotrimoxazol en infecciones óseas: toxicidad e impacto clínico y económico / Cotrimoxazole in bone-related infections: toxicity and clinical and economic impact

Background: Cotrimoxazole is a therapeutic option for bone-related infections but is associated to hyperkalemia and renal failure. Tolerance to this drug may reduce length of stay (LOS) and hospital charges. Aims: To evaluate renal, potassium toxicity, clinical outcome, and use of hospital resources in patients treated with cotrimoxazole for bone-related infections. Methods: Retrospective analysis of adult patients with bone-related infections confirmed by culture and treated with this drug. Serum potassium and creatinine levels were analyzed during follow-up and risk factors for hyperkalemia were searched. Length of stay (LOS) and hospital charges were compared. Clinical outcome was evaluated as a secondary endpoint. Results: From 2011 to 2014, 23 patients were identified (mean age 64.7 years). Diabetes mellitus, peripheral vascular disease, and previous amputations prevalence were high (82.6%, 47.8%, and 43.5%, respectively). Median serum potassium concentration increased significantly at first control (4.35 mEq/L to 4.9 mEq/L; p < 0.001), and also creatinine serum concentration (0.9 to 1.1 mg/dL; p < 0.05). Seven patients developed hyperkalemia. Cotrimoxazole was discontinued in 10 patients (43.5%), and in 6, discharge was postponed. Drugs active against the renin-angiotensin system (DAARAS) were associated with kyperkalemia (OR 10.8 IC95 1.37-85; p < 0.05). LOS was higher among patients with cotrimoxazole toxicity (median LOS 56 versus 30 days, p < 0.05). Patients with no cotrimoxazole interruption had less drug-related hospital charges (median values of 563 versus 2820 USD, respectively; p < 0.01). Conclusions: Cotrimoxazole use must be monitored in order to detect hyperkalemia or renal toxicity and suspend its prescription. Patients that use DAARAS have a higher risk of kyperkalemia. LOS and drug-related hospital charges are reduced when patients can tolerate cotrimoxazole.

Antecedentes: Cotrimoxazol es una alternativa en infecciones óseas pero se ha asociado al desarrollo de falla renal e hiperkalemia. Objetivo: Evaluar toxicidad renal, hiperkalemia, estadía y gastos hospitalarios y evolución clínica en un grupo de pacientes con infecciones óseas tratados con este compuesto. Pacientes y Métodos: Estudio retrospectivo-descriptivo de pacientes adultos con infecciones óseas confirmadas con cultivos y tratados con este compuesto. Seguimiento de creatinina y kalemia y búsqueda de factores de riesgo para hiperkalemia, comparación de gastos y estadía hospitalaria y análisis de eficacia clínica. Resultados: Desde el año 2011 al 2014 se identificaron 23 pacientes (promedio de edad 64,7 años). La prevalencia de diabetes mellitus tipo 2 (82,6%), enfermedad vascular periférica (47,8%) y amputaciones previas (43,5%) fue elevada. La mediana de la kalemia basal aumentó significativamente al primer control (4,35 a 4,9 mEq/L) al igual que la creatinina plasmática (0,9 a 1,1 mg/dL). Siete pacientes desarrollaron hiperkalemia (30,4%). Se suspendió cotrimoxazol en 10 casos (43,5%) y en 6 casos se postergó el alta. El uso de fármacos activos contra el sistema renina-angiotensina (FASRA) se asoció a hiperkalemia (OR 10,8 IC95 1,37-85; p < 0,05). La estadía hospitalaria fue mayor en el grupo con toxicidad a cotrimoxazol (mediana de 56 versus 30 días; p < 0,05) y los pacientes sin suspensión de terapia tuvieron menos gastos por fármacos (medianas de 563 vs 2.820 USD, p < 0,01). Conclusiones: El uso de cotrimoxazol debe ser monitorizado para detectar hiperkalemia o toxicidad renal y suspender su prescripción. Los pacientes que usan FASRA tienen mayor riesgo de hiperkalemia. La estadía y gastos hospitalarios por fármacos son menores en pacientes que toleran el cotrimoxazol.

[Cotrimoxazole in bone-related infections: toxicity and clinical and economic impact]. / Cotrimoxazol en infecciones óseas: toxicidad e impacto clínico y económico.

BACKGROUND: Cotrimoxazole is a therapeutic option for bone-related infections but is associated to hyperkalemia and renal failure. Tolerance to this drug may reduce length of stay (LOS) and hospital charges. AIMS: To evaluate renal, potassium toxicity, clinical outcome, and use of hospital resources in patients treated with cotrimoxazole for bone-related infections. METHODS: Retrospective analysis of adult patients with bone-related infections confirmed by culture and treated with this drug. Serum potassium and creatinine levels were analyzed during follow-up and risk factors for hyperkalemia were searched. Length of stay (LOS) and hospital charges were compared. Clinical outcome was evaluated as a secondary endpoint. RESULTS: From 2011 to 2014, 23 patients were identified (mean age 64.7 years). Diabetes mellitus, peripheral vascular disease, and previous amputations prevalence were high (82.6%, 47.8%, and 43.5%, respectively). Median serum potassium concentration increased significantly at first control (4.35 mEq/L to 4.9 mEq/L; p < 0.001), and also creatinine serum concentration (0.9 to 1.1 mg/dL; p < 0.05). Seven patients developed hyperkalemia. Cotrimoxazole was discontinued in 10 patients (43.5%), and in 6, discharge was postponed. Drugs active against the renin-angiotensin system (DAARAS) were associated with kyperkalemia (OR 10.8 IC95 1.37-85; p < 0.05). LOS was higher among patients with cotrimoxazole toxicity (median LOS 56 versus 30 days, p < 0.05). Patients with no cotrimoxazole interruption had less drug-related hospital charges (median values of 563 versus 2820 USD, respectively; p < 0.01). CONCLUSIONS: Cotrimoxazole use must be monitored in order to detect hyperkalemia or renal toxicity and suspend its prescription. Patients that use DAARAS have a higher risk of kyperkalemia. LOS and drug-related hospital charges are reduced when patients can tolerate cotrimoxazole.

Coadministration of co-trimoxazole with sulfonylureas: hypoglycemia events and pattern of use.

BACKGROUND: Coadministration of co-trimoxazole with sulfonylureas is reported to increase the risk of hypoglycemia. METHODS: We identified a cohort of Medicare beneficiaries aged 66 years or older who took glyburide or glipizide for diabetes from a 5% national sample of Medicare Part D claims data in 2008 (n = 34,239). We tracked each participant's claims during 2008-2010 for a co-trimoxazole prescription and subsequent emergency room visits for hypoglycemia. Descriptive statistics and logistic regression modeling were used to evaluate hypoglycemia-related emergency room visits after coadministration of co-trimoxazole with sulfonylureas and its utilization patterns in older adults with diabetes. RESULTS: Sulfonylureas users prescribed co-trimoxazole had a significant higher risk of emergency room visits for hypoglycemia, compared with those prescribed noninteracting antibiotics (odds ratio = 3.89, 95% confidence interval = 2.29-6.60 for glipizide and odds ratio = 3.78, 95% confidence interval = 1.81-7.90 for glyburide with co-trimoxazole, using amoxicillin as the reference). Co-trimoxazole was prescribed to 16.9% of those taking glyburide or glipizide during 2008-2010, varying from 4.0% to 35.9% across U.S. hospital referral regions. Patients with polypharmacy and with more prescribers were more likely to receive co-trimoxazole. Patients with an identifiable primary care physician had 20% lower odds of receiving a co-trimoxazole prescription. Hospital referral regions with more PCPs had lower rates of coadministration of the two drugs (r = -.26, p < 0.001). CONCLUSIONS: Coadministration of co-trimoxazole with sulfonylureas is associated with increased risk of hypoglycemia, compared with noninteracting antibiotics. Such coadministration is prevalent among older diabetic patients in the United States, especially in patients without an identifiable primary care physician.

Hypoglycemia after antimicrobial drug prescription for older patients using sulfonylureas.

IMPORTANCE: Certain antimicrobial drugs interact with sulfonylureas to increase the risk of hypoglycemia. OBJECTIVE: To determine the risk of hypoglycemia and associated costs in older patients prescribed glipizide or glyburide who fill a prescription for an antimicrobial drug. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of Texas Medicare claims from 2006 to 2009 for patients 66 years or older who were prescribed glipizide or glyburide and who also filled a prescription for 1 of the 16 antimicrobials most commonly prescribed for this population. METHODS: We assessed hypoglycemia events and associated Medicare costs in patients prescribed 1 of 7 antimicrobial agents thought to interact with sulfonylureas, using noninteracting antimicrobials as a comparison. We used a repeated measure logistic regression, controlling for age, sex, ethnicity, Medicaid eligibility, comorbidity, prior emergency department visits for hypoglycemia, prior hospitalizations for any cause, nursing home residence, and indication for the antimicrobial. We estimated odds of hypoglycemia, number needed to harm, deaths during hospitalization for hypoglycemia, and Medicare costs for hypoglycemia treatment. MAIN OUTCOMES AND MEASURES: Any hospitalization or emergency department visit owing to hypoglycemia within 14 days of antimicrobial exposure. RESULTS: In multivariable analyses controlling for patient characteristics and indication for antimicrobial drug use, clarithromycin (odds ratio [OR], 3.96 [95% CI, 2.42-6.49]), levofloxacin (OR, 2.60 [95% CI, 2.18-3.10]), sulfamethoxazole-trimethoprim (OR, 2.56 [95% CI, 2.12-3.10]), metronidazole (OR, 2.11 [95% CI, 1.28-3.47]), and ciprofloxacin (OR, 1.62 [95% CI, 1.33-1.97]) were associated with higher rates of hypoglycemia compared with a panel of noninteracting antimicrobials. The number needed to harm ranged from 71 for clarithromycin to 334 for ciprofloxacin. Patient factors associated with hypoglycemia included older age, female sex, black or Hispanic race/ethnicity, higher comorbidity, and prior hypoglycemic episode. In 2009, 28.3% of patients prescribed a sulfonylurea filled a prescription for 1 of these 5 antimicrobials, which were associated with 13.2% of all hypoglycemia events in patients taking sulfonylureas. The treatment of subsequent hypoglycemia adds $30.54 in additional Medicare costs to each prescription of 1 of those 5 antimicrobials given to patients taking sulfonylureas. CONCLUSIONS AND RELEVANCE: Prescription of interacting antimicrobial drugs to patients on sulfonylureas is very common, and is associated with substantial morbidity and increased costs.

Risk of bleeding and antibiotic use in patients receiving continuous phenprocoumon therapy. A case-control study nested in a large insurance- and population-based German cohort.

There is major concern about coumarins interacting with various drug classes and increasing the risk of overanticoagulation. The aim of the study was to assess bleeding risk in patients with concurrent use of antibiotics and phenprocoumon, the most widely prescribed coumarin in many European countries. We conducted a nested-case-control study within a cohort of 513,338 incident and continuous phenprocoumon users ≥ 18 years of age using claims data of the statutory health insurance company AOK, covering 30% of the German population. Bleeding risk associated with current use of antibiotics for systemic use (antibacterials/antimycotics) was calculated using conditional logistic regression in 13,785 cases with a bleeding event and 55,140 risk-set sampling-matched controls. Bleeding risk associated with any antibacterial use in phenprocoumon users was significantly increased [odds ratio (OR) 2.37, 95% confidence interval (CI) 2.20-2.56]. The association was stronger for gastrointestinal than for cerebral bleeding (OR 2.09, 95% CI 1.84-2.38 and OR 1.34, 95% CI 1.03-1.74, respectively) and highest for other/unspecified bleeding (OR 2.92, 95% CI 2.62-3.26). Specific antibiotic classes were strongly associated with bleeding risk, e.g. cotrimoxazole (OR 3.86, 95% CI 3.08-4.84) and fluorquinolones (OR 3.13, 95% CI 2.74-3.59), among those highest for ofloxacin (OR 5.00, 95% CI 3.01-8.32). Combined use of phenprocoumon and antimycotics was not significantly associated with bleeding risk. Risk was not significantly modified by age (pint=0.25) or sex (pint=0.96). The association was stronger the closer the antibiotic exposure was to the bleeding event. Among continuous phenprocoumon users, antibiotics - particularly quinolones and cotrimoxazole - should be prescribed after careful consideration due to an increased bleeding risk. Close monitoring of international normalised ratio levels after prescription is recommended.

Urinary tract infection in male veterans: treatment patterns and outcomes.

BACKGROUND: Lengthier antimicrobial therapy is associated with increased costs, antimicrobial resistance, and adverse drug events. Therefore, establishing minimum effective antimicrobial treatment durations is an important public health goal. The optimal treatment duration and current treatment patterns for urinary tract infection (UTI) in men are unknown. We used Veterans Affairs administrative data to study male UTI treatment and outcomes. METHODS: Male UTI episodes in the Veterans Affairs system (fiscal year 2009) were identified by combining International Classification of Diseases, Ninth Revision codes with UTI-relevant antimicrobial prescriptions. Episodes were categorized as index, early recurrence (<30 days), or late recurrence (≥30 days) cases. Drug name, treatment duration, and outcomes (recurrence and Clostridium difficile infection during 12 months) were recorded for index cases. Demographic, clinical, and treatment characteristics were assessed for associations with outcomes in univariate and multivariate analyses. RESULTS: Among 4 854 765 outpatient male veterans, 39 149 UTI episodes involving 33 336 unique patients were identified, including 33 336 index cases (85.2%), 1772 early recurrences (4.5%), and 4041 late recurrences (10.3%). Highest-use antimicrobial agents were ciprofloxacin (62.7%) and trimethoprim-sulfamethoxazole (26.8%); 35.0% of patients received shorter-duration treatment (≤7 days), and 65.0% of patients received longer-duration treatment (>7 days). Of the index cases, 4.1% were followed by early recurrence and 9.9% by late recurrence. Longer-duration treatment was not associated with a reduction in early or late recurrence but was associated with increased late recurrence compared with shorter-duration treatment (10.8% vs 8.4%, P < .001), including in multivariate analysis (odds ratio, 1.20; 95% CI, 1.10-1.30). In addition, C difficile infection risk was significantly higher with longer-duration vs shorter-duration treatment (0.5% vs 0.3%, P = .02) and exhibited a similar suggestive trend in multivariate analysis (odds ratio, 1.42; 95% CI, 0.97-2.07). CONCLUSION: Longer-duration treatment (>7 days) for male UTI in the outpatient setting was associated with no reduction in early or late recurrence.

Unintended effects of a computerized physician order entry nearly hard-stop alert to prevent a drug interaction: a randomized controlled trial.

BACKGROUND: The effectiveness of computerized physician order entry (CPOE) systems has been modest, largely because clinicians frequently override electronic alerts. METHODS: To evaluate the effectiveness of a nearly "hard stop" CPOE prescribing alert intended to reduce concomitant orders for warfarin and trimethoprim-sulfamethoxazole, a randomized clinical trial was conducted at 2 academic medical centers in Philadelphia, Pennsylvania. A total of 1981 clinicians were assigned to either an intervention group receiving a nearly hard stop alert or a control group receiving the standard practice. The study duration was August 9, 2006, through February 13, 2007. RESULTS: The proportion of desired responses (ie, not reordering the alert-triggering drug within 10 minutes of firing) was 57.2% (111 of 194 hard stop alerts) in the intervention group and 13.5% (20 of 148) in the control group (adjusted odds ratio, 0.12; 95% confidence interval, 0.045-0.33). However, the study was terminated early because of 4 unintended consequences identified among patients in the intervention group: a delay of treatment with trimethoprim-sulfamethoxazole in 2 patients and a delay of treatment with warfarin in another 2 patients. CONCLUSIONS: An electronic hard stop alert as part of an inpatient CPOE system seemed to be extremely effective in changing prescribing. However, this intervention precipitated clinically important treatment delays in 4 patients who needed immediate drug therapy. These results illustrate the importance of formal evaluation and monitoring for unintended consequences of programmatic interventions intended to improve prescribing habits. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00870298.

Recurrent optic disc and retinal vasculitis in a patient with drug-induced urticarial vasculitis.

The purpose of this study was to report recurrent optic disc and retinal vasculitis in a patient with drug-induced urticarial vasculitis. Complete ophthalmological examination including fluorescein angiography and visual field examination were done. A 53-year-old woman with recurrent painful urticarial skin lesions following trimethoprim sulfamethoxazole usage had the clinical and histopathological diagnosis of urticarial vasculitis. Two years after cutaneous manifestations, she began to notice visual disturbances in both eyes that recurred at 1-year intervals. Her ophthalmological findings were consistent with recurrent vasculitis of the optic nerve and retina. Treatment with high-dose corticosteroids and hydroxychloroquine resulted in the resolution of cutaneous and ocular manifestations. This patient demonstrates that recurrent occlusive vasculitis of the optic nerve and retina can occur in this rare disease. These patients should be examined periodically by ophthalmologists.

Quality improvement case study: warfarin sodium interactions.

TOPIC: Dangerous Interactions Involving Antibiotic Use In Warfarin-Treated Nursing Facility Residents FACTS OF THE INCIDENT: All names, places and dates and some details have been changed to protect the confidentiality of this actual event.

Evidence assessment of management of acute otitis media: I. The role of antibiotics in treatment of uncomplicated acute otitis media.

CONTEXT: In 1995, >5 million episodes of acute otitis media (AOM) accounted for $3 billion in health care expenditures. OBJECTIVES: To synthesize the literature on the natural history of AOM, the effectiveness of antibiotic treatment in uncomplicated AOM, and the relative effectiveness of specific antibiotic regimens. DATA SOURCES: Seven electronic databases for articles published between 1966 and March 1999 and reference lists in proceedings, published articles, reports, and guidelines. STUDY SELECTION: Two physicians independently assessed each article. Studies addressing AOM in children 4 weeks to 18 years old were included; those addressing children with immunodeficiencies or craniofacial abnormalities were excluded. Randomized, controlled trials (RCTs) were used to assess antibiotic effectiveness, and RCTs and cohort studies were used to assess the natural history of AOM. Among the 3491 citations identified, 80 (2.3%) met our inclusion criteria. DATA EXTRACTION: Two physicians independently abstracted data and assessed the quality of studies using a validated scale for RCTs and 8 quality components for cohort studies. DATA SYNTHESIS: Random-effects estimates of pooled absolute rate differences of outcomes were derived, and heterogeneity of both the rates and rate differences was assessed. Children with AOM not treated with antibiotics experienced a 1- to 7-day clinical failure rate of 19% (95% confidence interval: 0.10-0.28) and few suppurative complications. When patients were treated with amoxicillin, the 2- to 7-day clinical failure rate was reduced to 7%, a 12% (95% confidence interval: 0.04-0.20) reduction. Adverse effects, primarily gastrointestinal, were more common among children on cefixime than among those on ampicillin or amoxicillin. They were also more common among children on amoxicillin-clavulanate than among those on azithromycin. CONCLUSIONS: The majority of uncomplicated cases of AOM resolve spontaneously without apparent suppurative complications. Ampicillin or amoxicillin confers a limited therapeutic benefit. There is no evidence to support any particular antibiotic regimens as more effective at relieving symptoms. Certain antibiotics are more likely than others to cause diarrhea and other adverse events.

Analysis of life-long strategies to prevent Pneumocystis carinii pneumonia in patients with variable HIV progression rates.

OBJECTIVE: To compare strategies for life-long prophylaxis of Pneumocystis carinii pneumonia (PCP) in a group of AIDS patients with a wide range of disease progression rates. DESIGN: Markov decision models. METHODS: Prophylaxis strategies using high and low doses of trimethoprim-sulfamethoxazole (TS), dapsone, and/or aerosolized pentamidine in sequence, were compared. Efficacy and toxicity rates for prophylaxis regimens were taken from a meta-analysis of pertinent randomized controlled trials. Outcomes measured included lifetime episodes of PCP and drug toxicity per 100 patients treated, average life expectancy, and cost. RESULTS: For patients with an expected survival of 3 years after commencement of prophylaxis, the use of standard or low dose TS as the first choice agent was comparable, and both were superior to the other strategies for preventing PCP (between nine and 26 fewer episodes of PCP per 100 patients treated) though they were more toxic (11-44 more episodes of toxicity per 100 patients treated). Life expectancy was similar for all of the treatment strategies. With slower rates of disease progression (expected survival > 3.8 years), as seen with current antiretroviral regimens, the use of low dose TS as the first choice agent dominated the use of standard dose TS; when the expected survival time was 7 years, initial use of low dose TS led to 2.8 fewer episodes of PCP per 100 patients treated, 32 fewer episodes of toxicity per 100 patients treated, and US$1381 per patient lower cost, compared with prophylaxis with standard dose TS. CONCLUSION: For patients with AIDS and expected survival > 3.8 years, low dose TS is better than standard dose TS as the first choice agent for preventing PCP. As patients with AIDS live longer, the routine use of low dose TS will be more than adequate for patients at risk for PCP.

Trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in cirrhosis: a randomized trial.

OBJECTIVE: To assess the efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis and ascites. DESIGN: A randomized controlled trial. SETTING: University-affiliated Veterans Affairs medical center. PATIENTS: 60 consecutive patients with cirrhosis and ascites. INTERVENTIONS: Consecutive patients were randomly assigned to receive either no prophylaxis or trimethoprim-sulfamethoxazole, one double-strength tablet daily, five times a week (Monday through Friday). Patient entry was stratified by serum bilirubin (> 51 mumol/L [> 3 mg/dL]), ascitic fluid protein (< 1 g/dL), and serum creatinine (> 177 mumol/L [> 2 mg/dL]) levels to ensure that high-risk patients would be similarly distributed in the two groups. The median duration of follow-up for the study patients was 90 days. MAIN OUTCOME MEASURES: Spontaneous bacterial peritonitis or spontaneous bacteremia as defined by objective criteria. RESULTS: Spontaneous bacterial peritonitis or spontaneous bacteremia developed in 27% (8 of 30) of patients who did not receive prophylaxis compared with 3% (1 of 30) of patients receiving trimethoprim-sulfamethoxazole (P = 0.025). Overall, infections developed in 9 of 30 patients (30%) not receiving prophylaxis and in 1 of 30 patients (3%) receiving trimethoprim-sulfamethoxazole (P = 0.012). Death occurred in 6 of 30 patients (20%) who did not receive prophylaxis and in 2 of 30 patients (7%) who received trimethoprim-sulfamethoxazole (P = 0.15). Side effects--particularly, hematologic toxicity--could not be attributed to trimethoprim-sulfamethoxazole in any patient. CONCLUSIONS: Trimethoprim-sulfamethoxazole was efficacious, safe, and cost-effective for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis.

Pain assessment after intramuscular injection.

Several parameters (pH, osmotic pressure) influencing the local tolerance of injectable drugs have been well-documented; however, little attention has been paid to pain following an injection--a common problem in clinical practice. A pain questionnaire was used to record pain up to 24 h after a deep ventrogluteal injection. Two groups of healthy volunteers were recruited: the first group (n = 6) received 3 different cotrimoxazole preparations and placebo and the second group (n = 10) received 4 different multivitamin preparations and placebo (double-blind, cross-over). Parameters monitored during and after injection included pain localization (line drawing), pain intensity (visual-analog scale: VAS) and verbal description of pain (pain rating index: PRI). In both groups, the equality of pain (VAS, PRI) induced by the preparations was rejected in all cases (Friedman's test, p < or = 1%). The pairwise comparisons of the groups showed significant differences (p < or = 5%) between various preparations. The correlation (Spearman's rank correlation) between pain parameters VAS and PRI was high. The present investigations have shown that the pain questionnaire is a valuable tool to investigate the subjective pain symptoms during and after the injection of different preparations.

Clostridium difficile colonization in residents of long-term care facilities: prevalence and risk factors.

OBJECTIVE: To determine the period prevalence of Clostridium difficile disease and asymptomatic carriage in the residents of long-term care facilities (LTCF) and to characterize the risk factors for colonization or associated disease. DESIGN: Period prevalence survey. SETTING: Two long-term care facilities in St. Paul, MN. PARTICIPANTS: Specimens were collected from 225 LTCF residents. MEASUREMENTS: The dependent variable was the culture result for C. difficile, which was isolated and identified using selective culture media and a commercial anaerobe identification kit. Tissue culture assay was used to detect the ability of each C. difficile isolate to produce toxin. Independent variables (including gender, age, race, current medical diagnoses, severity of underlying disease, case mix, current clinical symptoms, current medications, antibiotic use within 4 weeks prior to specimen procurement, and other pertinent history) were obtained from the current medical record of each participant. RESULTS: Of 225 stool cultures that were obtained, 16 (7.1%) were positive for C. difficile. None of the residents with a positive culture was symptomatic. History of nosocomial infection and the use of antibiotics in general, cephalosporins, trimethoprim/sulfamethoxazole (TMP/SMX), and histamine-2 blockers were significantly associated with positive C. difficile culture (P < or = 0.05) by univariate analyses. Trends towards significance (0.05 < 0.10) were noted for narcotic use, previous hospitalization, LTCF, and non-insulin-dependent diabetes mellitus. Logistic regression analysis revealed significant, independent predictors of positive culture: antibiotic use in general (P = 0.028; relative risk = 3.31), histamine-2 antagonist use (P = 0.038; relative risk = 3.27), cephalosporin use (P = 0.038; relative risk = 4.66), and TMP/SMX use (P = 0.007; relative risk = 8.45). CONCLUSIONS: The use of antibiotics, particularly cephalosporins and TMP/SMX, is a significant risk factor for asymptomatic carriage of C. difficile in long-term care facilities. The use of H-2 blockers was also a significant risk factor for carriage; however, this finding has not been reported previously and should be confirmed by independent studies. These medications should be used judiciously in the LTCF population. When diarrheal diseases are encountered in LTCF residents, a high index of suspicion for C. difficile infection should be maintained and the appropriate diagnostic and therapeutic measures taken.

Cost and benefit of secondary prophylaxis for Pneumocystis carinii pneumonia.

OBJECTIVE: To determine the relative cost and benefit of aerosolized pentamidine and the combination product of sulfamethoxazole and trimethoprim sulfate as secondary prophylaxis for Pneumocystis carinii pneumonia. DESIGN: A Markov-based cost-benefit analysis was performed. Drug efficacies, toxicities, and mortality rates were drawn from the current literature. SETTING: Hypothetical. PATIENT POPULATION: Patients infected with the human immunodeficiency virus who had had at least one episode of P carinii pneumonia. INTERVENTIONS: Regimen 1 required the use of aerosolized pentamidine as the sole first-line prophylactic agent in all patients. Regimen 2 required the use of sulfamethoxazole-trimethoprim in all patients who had no history of a toxic reaction to the drug; only patients with a history of toxic effects and those who developed toxic effects while receiving the drug would receive aerosolized pentamidine. Regimen 3 required that no secondary prophylaxis be given. MAIN OUTCOME MEASURES: Net cost, median patient survival, and 5-year survival for each regimen and for regimens 1 and 2 compared with regimen 3. MAIN RESULTS: Regimen 2 was dominant, with a net cost of $6332 per patient and a median survival of 2.050 years. Compared with no prophylaxis, regimen 2 resulted in a savings of $16,503 per patient and a 0.696-year increase in median survival. Compared with regimen 1, regimen 2 resulted in a savings of $2904 and a 0.067-year increase in median survival. CONCLUSIONS: Secondary prophylaxis for P carinii saves money and extends survival. Current data suggest that sulfamethoxazole-trimethoprim should be given whenever it can be tolerated. Use of aerosolized pentamidine as a first-line agent would result in a modest increase in cost and a decrease in life expectancy.