Sulfonamide desensitization in solid organ transplant recipients: A protocol-driven approach during the index transplant hospitalization.

Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line agent for Pneumocystis jiroveci pneumonia (PJP) prophylaxis for solid organ transplant (SOT) recipients because of its efficacy for this indication, extended antimicrobial coverage, and favorable cost. Reported sulfonamide allergy is not uncommon and often results in TMP-SMX avoidance. Desensitization offers an efficacious and cost-effective alternative to TMP-SMX avoidance. Herein, we reviewed our experience with desensitization during the index transplant hospitalization among 52 SOT recipients with history of a non-anaphylactic sulfonamide allergy. Of those enrolled in the desensitization protocol, 92% (48/52) completed the protocol, with nearly 80% (41/52) still on TMP-SMX at 3 months without adverse reaction. Eleven patients discontinued TMP-SMX (7 for allergic reactions and 4 for non-allergic reasons) and switched to pentamidine. A cost savings of $575 per desensitization was calculated based on annual wholesale drug prices, for a total savings of $23 575. Additionally, the protocol did not delay discharge in any patient nor was it associated with any severe allergic reactions. These findings suggest TMP-SMX desensitization is safe and effective in SOT recipients with a history of non-anaphylactic, non-life-threatening sulfonamide hypersensitivity.

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.

Antibacterial Susceptibilities of Escherichia coli from Community-Acquired Urinary Tract Infections in the Faroe Islands, Associations with Antibacterial Sales, and Comparison with Iceland and Denmark.

Currently, data on Escherichia coli antibacterial susceptibilities in the Faroe Islands are lacking. The aim was to investigate the antibacterial susceptibilities of E. coli from patients with community-acquired urinary tract infections in the Faroe Islands, correlate with antibacterial sales, and compare with Iceland and Denmark. From 2009 to 2010 and in 2012, 12 general practitioners from the Faroe Islands were recruited to provide urine samples from patients. Antibacterial susceptibilities were determined by disc diffusion testing according to the Clinical and Laboratory Standards Institute methods and criteria. Logistic regression (quasibinomial) of the antibacterial resistance proportions versus mean sales during the period of 2008-2011 was used to determine association. Nonsusceptibility to at least 1 of the 14 antibacterial drugs investigated was found in 54% of the E. coli isolates and was most common to ampicillin (46%), followed by sulfamethoxazole (39%), trimethoprim (27%), trimethoprim/sulfamethoxazole (27%), and <10% to the remaining 10 antibiotics. The resistance prevalence did not change significantly with time. From logistic regression modeling, we find significant associations between antibacterial mean sales and antibacterial resistances. For the resistances in the Faroe Islands compared with data from Denmark and Iceland, we infer two groups of resistances indicating different responses-one steep and one gradual-to antibacterial sales. For these two groups, we find ß1 = 4.77 (Std. Error = 0.624, p-value = 0.002) and ß1 = 0.26 (Std. Error = 0.020, p-value = 4e-7) for the steep and gradual groups, respectively. This knowledge can potentially be used to predict and control the future increase in E. coli resistance with antibacterial sales.

Impact of alternative treatment approach for cerebral toxoplasmosis among HIV/AIDS patients from a resource-poor setting in Burkina Faso

Cerebral toxoplasmosis is caused by the protozoan Toxoplasma gondii because of reactivation of latent tissue cysts in the Acquired Immunodeficiency Syndrome (AIDS) patients with severe immunosuppression. The objective of this study was to evaluate the benefit of co-trimoxazole in presumptive and prevention of cerebral toxoplasmosis in Human Immunodeficiency Virus (HIV)/AIDS patients at Bobo-Dioulasso Hospital in Burkina Faso from June 2012 to October 2014. ELISA and ELFA were performed on serum for the quantitative determination of IgG and IgM anti-T. gondii, respectively. The seroprevalence of toxoplasmosis was 29.3%. No IgM antibodies for T. gondii were found. Six patients with Toxoplasma-specific antibodies presented cerebral toxoplasmosis. All patients were infected by HIV-1 with the median of CD4+ T lymphocytes at 141 cells/µl. No patient was under antiretroviral therapy. No case of cerebral toxoplasmosis was noted in patients receiving co-trimoxazole in prevention. Presumptive treatment of cerebral toxoplasmosis with co-trimoxazole was effective in all patients with a significant clinical improvement in 83.3%. These results attest the benefit of cotrimoxazole in cerebral toxoplasmosis treatment in countries where drug resources are limited when sulfadiazine is not available. Ours finding highlight the importance of establishing toxoplasmosis chemoprophylaxis to HIV with severe immunosuppression patients and positive Toxoplasma serology.

Cost-effectiveness of malaria preventive treatment for HIV-infected pregnant women in sub-Saharan Africa.

BACKGROUND: Malaria is a leading cause of morbidity and mortality among HIV-infected pregnant women in sub-Saharan Africa: at least 1 million pregnancies among HIV-infected women are complicated by co-infection with malaria annually, leading to increased risk of premature delivery, severe anaemia, delivery of low birth weight infants, and maternal death. Current guidelines recommend either daily cotrimoxazole (CTX) or intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) for HIV-infected pregnant women to prevent malaria and its complications. The cost-effectiveness of CTX compared to IPTp-SP among HIV-infected pregnant women was assessed. METHODS: A microsimulation model of malaria and HIV among pregnant women in five malaria-endemic countries in sub-Saharan Africa was constructed. Four strategies were compared: (1) 2-dose IPTp-SP at current IPTp-SP coverage of the country ("2-IPT Low"); (2) 3-dose IPTp-SP at current coverage ("3-IPT Low"); (3) 3-dose IPTp-SP at the same coverage as antiretroviral therapy (ART) in the country ("3-IPT High"); and (4) daily CTX at ART coverage. Outcomes measured include maternal malaria, anaemia, low birth weight (LBW), and disability-adjusted life years (DALYs). Sensitivity analyses assessed the effect of adherence to CTX. RESULTS: Compared with the 2-IPT Low Strategy, women receiving CTX had 22.5% fewer LBW infants (95% CI 22.3-22.7), 13.5% fewer anaemia cases (95% CI 13.4-13.5), and 13.6% fewer maternal malaria cases (95% CI 13.6-13.7). In all simulated countries, CTX was the preferred strategy, with incremental cost-effectiveness ratios ranging from cost-saving to $3.9 per DALY averted from a societal perspective. CTX was less effective than the 3-IPT High Strategy when more than 18% of women stopped taking CTX during the pregnancy. CONCLUSION: In malarious regions of sub-Saharan Africa, daily CTX for HIV-infected pregnant women regardless of CD4 cell count is cost-effective compared with 3-dose IPTp-SP as long as more than 82% of women adhere to daily dosing.

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.

The costs of providing antiretroviral therapy services to HIV-infected individuals presenting with advanced HIV disease at public health centres in Dar es Salaam, Tanzania: Findings from a randomised trial evaluating different health care strategies.

BACKGROUND: Understanding the costs associated with health care delivery strategies is essential for planning. There are few data on health service resources used by patients and their associated costs within antiretroviral (ART) programmes in Africa. MATERIAL AND METHODS: The study was nested within a large trial, which evaluated screening for cryptococcal meningitis and tuberculosis and a short initial period of home-based adherence support for patients initiating ART with advanced HIV disease in Tanzania and Zambia. The economic evaluation was done in Tanzania alone. We estimated costs of providing routine ART services from the health service provider's perspective using a micro-costing approach. Incremental costs for the different novel components of service delivery were also estimated. All costs were converted into US dollars (US$) and based on 2012 prices. RESULTS: Of 870 individuals enrolled in Tanzania, 434 were enrolled in the intervention arm and 436 in the standard care/control arm. Overall, the median (IQR) age and CD4 cell count at enrolment were 38 [31, 44] years and 52 [20, 89] cells/mm3, respectively. The mean per patient costs over the first three months and over a one year period of follow up following ART initiation in the standard care arm were US$ 107 (95%CI 101-112) and US$ 265 (95%CI 254-275) respectively. ART drugs, clinic visits and hospital admission constituted 50%, 19%, and 19% of the total cost per patient year, while diagnostic tests and non-ART drugs (co-trimoxazole) accounted for 10% and 2% of total per patient year costs. The incremental costs of the intervention to the health service over the first three months was US$ 59 (p<0.001; 95%CI 52-67) and over a one year period was US$ 67(p<0.001; 95%CI 50-83). This is equivalent to an increase of 55% (95%CI 51%-59%) in the mean cost of care over the first three months, and 25% (95%CI 20%-30%) increase over one year of follow up.

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.

Opportunities for improving the efficiency of paediatric HIV treatment programmes.

OBJECTIVES: To conduct two economic analyses addressing whether to: routinely monitor HIV-infected children on antiretroviral therapy (ART) clinically or with laboratory tests; continue or stop cotrimoxazole prophylaxis when children become stabilized on ART. DESIGN AND METHODS: The ARROW randomized trial investigated alternative strategies to deliver paediatric ART and cotrimoxazole prophylaxis in 1206 Ugandan/Zimbabwean children. Incremental cost-effectiveness and value of implementation analyses were undertaken. Scenario analyses investigated whether laboratory monitoring (CD4 tests for efficacy monitoring; haematology/biochemistry for toxicity) could be tailored and targeted to be delivered cost-effectively. Cotrimoxazole use was examined in malaria-endemic and non-endemic settings. RESULTS: Using all trial data, clinical monitoring delivered similar health outcomes to routine laboratory monitoring, but at a reduced cost, so was cost-effective. Continuing cotrimoxazole improved health outcomes at reduced costs. Restricting routine CD4 monitoring to after 52 weeks following ART initiation and removing toxicity testing was associated with an incremental cost-effectiveness ratio of $6084 per quality-adjusted life-year (QALY) across all age groups, but was much lower for older children (12+ years at initiation; incremental cost-effectiveness ratio = $769/QALY). Committing resources to improve cotrimoxazole implementation appears cost-effective. A healthcare system that could pay $600/QALY should be willing to spend up to $12.0 per patient-year to ensure continued provision of cotrimoxazole. CONCLUSION: Clinically driven monitoring of ART is cost-effective in most circumstances. Routine laboratory monitoring is generally not cost-effective at current prices, except possibly CD4 testing amongst adolescents initiating ART. Committing resources to ensure continued provision of cotrimoxazole in health facilities is more likely to represent an efficient use of resources.

Improving rates of cotrimoxazole prophylaxis in resource-limited settings: implementation of a quality improvement approach.

OBJECTIVE: To demonstrate the effectiveness of quality improvement methods to monitor and improve administration of cotrimoxazole (CTX) prophylaxis to improve health outcomes among adults living with HIV/AIDS in low resource countries. DESIGN: Program evaluation. SETTING: HIV/AIDS health care facilities in Uganda, Mozambique, Namibia and Haiti. INTERVENTION: Performance measures based on national guidelines are developed in each country. These may include CD4 monitoring, ART adherence and uptake of CTX prophylaxis. CTX prophylaxis is routinely selected, because it has been shown to reduce HIV-related morbidity and mortality. Patient records are sampled using a standard statistical table to achieve a minimum confidence interval of 90% with a spread of ±8% in participating clinics. If an electronic medical record is available, all patients are reviewed. Routine review of performance measures, usually every 6 months, is conducted to identify gaps in care. Improvement interventions are developed and implemented at health facilities, informed by performance results, and local/national public health priorities. MAIN OUTCOME MEASURE: Median clinic rates of CTX prophylaxis. RESULTS: Median performance rates of CTX prophylaxis generally improved for adult HIV+ patients between 2006 and 2013 across countries, with median clinic rates higher than baseline at follow-up in 16 of 18 groups of clinics implementing CTX -focused improvement projects. CONCLUSIONS: Quality management offers a data-driven method to improve the quality of HIV care in low resource countries. Application of improvement principles has been shown to be effective to increase the rates of CTX prophylaxis in national HIV programs in multiple countries.

Cost-effectiveness of cranberries vs antibiotics to prevent urinary tract infections in premenopausal women: a randomized clinical trial.

BACKGROUND: Urinary tract infections (UTIs) are common and result in an enormous economic burden. The increasing prevalence of antibiotic-resistant microorganisms has stimulated interest in non-antibiotic agents to prevent UTIs. OBJECTIVE: To evaluate the cost-effectiveness of cranberry prophylaxis compared to antibiotic prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) over a 12 month period in premenopausal women with recurrent UTIs. MATERIALS AND METHODS: An economic evaluation was performed alongside a randomized trial. Primary outcome was the number of UTIs during 12 months. Secondary outcomes included satisfaction and quality of life. Healthcare utilization was measured using questionnaires. Missing data were imputed using multiple imputation. Bootstrapping was used to evaluate the cost-effectiveness of the treatments. RESULTS: Cranberry prophylaxis was less effective than TMP-SMX prophylaxis, but the differences in clinical outcomes were not statistically significant. Costs after 12 months in the cranberry group were statistically significantly higher than in the TMP-SMX group (mean difference €249, 95% confidence interval 70 to 516). Cost-effectiveness planes and cost-effectiveness acceptability curves showed that cranberry prophylaxis to prevent UTIs is less effective and more expensive than (dominated by) TMP-SMX prophylaxis. CONCLUSION: In premenopausal women with recurrent UTIs, cranberry prophylaxis is not cost-effective compared to TMP-SMX prophylaxis. However, it was not possible to take into account costs attributed to increased antibiotic resistance within the framework of this randomized trial; modeling studies are recommended to investigate these costs. Moreover, although we based the dosage of cranberry extract on available evidence, this may not be the optimal dosage. Results may change when this optimal dosage is identified. TRIAL REGISTRATION: ISRCTN.org ISRCTN50717094.

Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: an economic evaluation alongside a randomised controlled trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fibrotic disease of the lungs of unknown origin with a poor prognosis. A small trial of co-trimoxazole demonstrated improvements in symptoms and functional parameters over a 3-month period. We therefore conducted a larger trial with a concurrent economic evaluation to investigate this antibiotic further. METHODS: We report an economic evaluation alongside a multi-centre, randomised, placebo-controlled, double-blind trial of 12 months therapy with 960 mg co-trimoxazole daily in 181 patients with fibrotic idiopathic interstitial pneumonia (IIP). Patients were recruited from 28 university and district hospitals in the UK and were aged over 40 years with fibrotic IIP. We report costs to the National Health Service (NHS) and society, change in forced vital capacity (primary endpoint) and quality-adjusted life-years (QALYs) gained, incremental cost effectiveness and cost utility ratios over 12 months. RESULTS: From the perspective of society, mean cost per patient in the co-trimoxazole arm was approximately £1177 higher than in the placebo arm, but mean QALYs were 0.053 higher yielding an incremental cost-effectiveness ratio of £22,012 per QALY gained with a 54.44 % probability of being below £30,000. The cost of IPF to UK society in 2011 is tentatively estimated at £124 million, of which 13 % is NHS costs, 1 % social services, 2 % patient out-of-pocket costs and 84 % lost productivity. CONCLUSIONS: Given commonly employed thresholds in the UK NHS, on balance co-trimoxazole may be a cost-effective treatment for IPF, although there is substantial decision uncertainty. However, recent guidance on the use of immunosuppressive therapy in IPF patients should be taken into account prior to any policy decision.

A practical guide to community-acquired MRSA.

As the number of CA-MRSA skin and soft tissue infections continues to grow, it's important to know which patients are at greatest risk and which evidence-based treatment protocols to turn to when needed.

Treatment of methicillin-resistant Staphylococcus aureus infections with a minimal inhibitory concentration of 2 µg/mL to vancomycin: old (trimethoprim/sulfamethoxazole) versus new (daptomycin or linezolid) agents.

BACKGROUND: Guidelines recommend that agents other than vancomycin be considered for some types of infection due to methicillin-resistant Staphylococcus aureus (MRSA) when the minimum inhibitory concentration (MIC) to vancomycin is 2 µg/mL or more. Alternative therapeutic options include daptomycin and linezolid, 2 relatively new and expensive drugs, and trimethoprim/sulfamethoxazole (TMP/SMX), an old and inexpensive agent. OBJECTIVE: To compare the clinical efficacy and potential cost savings associated with use of TMP/SMX compared to linezolid and daptomycin. METHODS: A retrospective study was conducted at Detroit Medical Center. For calendar year 2009, unique adults (age >18 years) with infections due to MRSA with an MIC to vancomycin of 2 µg/mL were included if they received 2 or more doses of TMP/SMX and/or daptomycin and/or linezolid. Data were abstracted from patient charts and pharmacy records. RESULTS: There were 328 patients included in the study cohort: 143 received TMP/SMX alone, 89 received daptomycin alone, 75 received linezolid alone, and 21 patients received a combination of 2 or more of these agents. In univariate analysis, patients who received TMP/SMX alone had significantly better outcomes, including in-hospital (p = 0.003) and 90-day mortality (p < 0.001) compared to patients treated with daptomycin or linezolid. Patients receiving TMP/SMX were also younger (p < 0.001), had fewer comorbid conditions (p < 0.001), had less severe acute severity of illness (p < 0.001), and received appropriate therapy more rapidly (p = 0.001). In multivariate models the association between TMP/SMX treatment and mortality was no longer significant. Antimicrobial cost savings associated with using TMP/SMX averaged $2067.40 per patient. CONCLUSIONS: TMP/SMX monotherapy compared favorably to linezolid and daptomycin in terms of treatment efficacy and mortality. Use of TMP/SMX instead of linezolid or daptomycin could potentially significantly reduce antibiotic costs. TMP/SMX should be considered for the treatment of MRSA infection with MIC of 2 µg/mL to vancomycin.

The cost-effectiveness of cotrimoxazole in people with advanced HIV infection initiating antiretroviral therapy in sub-Saharan Africa.

BACKGROUND: In sub-Saharan Africa, high mortality rates have been reported among patients with advanced HIV infection initiating antiretroviral therapy (ART). We evaluated the cost-effectiveness of expanding access to cotrimoxazole (CTX) for persons with HIV in averting mortality during the first 6 months of ART. We also evaluated possible cost savings related to prevention of specific opportunistic infections (OIs). METHODS: We developed a decision-analytic model to estimate the incremental cost, deaths averted, and incremental cost-effectiveness ratio. The model compared 2 scenarios for providing CTX and evaluated potential benefits of increased CTX coverage in reducing deaths and cases of OI. The base case scenario represents an estimated current level of CTX coverage among adults initiating ART in low-income countries (65%). The comparator is 97% coverage (excluding only those with contraindications to CTX). We conducted sensitivity analyses on all parameters in the model. RESULTS: Full coverage reduced deaths from 94 to 72 per 1000 patients, averting 22 deaths during the first 6 months of ART compared with the base case. The incremental cost of moving from base case to full coverage was estimated at $3.29 per person on ART and $146.91 per death averted over 6 months. Additional benefits from averted OI cases would likely be realized as well as savings from averted OI treatment costs. CONCLUSIONS: Our findings suggest that expanding CTX coverage is a cost-effective approach to reducing mortality among patients who present with advanced HIV and initiate ART. The expansion of coverage may also yield benefits for OIs.

Implementation of free cotrimoxazole prophylaxis improves clinic retention among antiretroviral therapy-ineligible clients in Kenya.

OBJECTIVE: To determine whether implementation of free cotrimoxazole (CTX) provision was associated with improved retention among clients ineligible for antiretroviral therapy (ART) enrolled in an HIV treatment program in Kenya. DESIGN: Data were obtained from a clinical cohort for program evaluation purposes. Twelve-month clinic retention was compared among ART-ineligible clients enrolled in the time period before free CTX versus the time period after. METHODS: Statistical comparisons were made using Kaplan-Meier survival curves, log-rank tests, and multivariate Cox proportional hazards models. To exclude potential temporal program changes that may have influenced retention, ART clients before and after the same cut-off date were compared. FINDINGS: Among adult clients enrolled between 2005 and 2007, 3234 began ART within 1 year of enrollment, and 1024 of those who did not start treatment were defined as ART-ineligible. ART-ineligible clients enrolled in the period following free CTX provision had higher 12-month retention (84%) than those who enrolled prior to free CTX (63%; P < 0.001). Retention did not change significantly during these periods among ART clients (P = 0.55). In multivariate analysis, ART-ineligible clients enrolled prior to free CTX were more than twice as likely to be lost to follow-up compared to those following free CTX [adjusted hazard ratio (aHR) = 2.64, 95% confidence interval 1.95-3.57, P < 0.001]. CONCLUSION: Provision of free CTX was associated with significantly improved retention among ART-ineligible clients. Retention and CD4-monitoring of ART-ineligible clients are essential to promptly identify ART eligibility and provide treatment. Implementation of free CTX may improve retention in sub-Saharan Africa and, via increasing timely ART initiation, provide survival benefit.

Nitrofurantoin compares favorably to recommended agents as empirical treatment of uncomplicated urinary tract infections in a decision and cost analysis.

OBJECTIVE: To analyze the costs of nitrofurantoin use compared to those of other antibiotics recommended for treatment of uncomplicated urinary tract infection (UTI). PATIENTS AND METHODS: We used a decision analysis model to perform cost-minimization and sensitivity analyses to determine the level of trimethoprim-sulfamethoxazole (TMP-SMX) and fluoroquinolone resistance that would favor the use of nitrofurantoin as a first-line empirical treatment of uncomplicated UTIs. The model used a program perspective to evaluate costs. RESULTS: Nitrofurantoin was cost-minimizing when the prevalence of fluoroquinolone resistance exceeded 12% among uropathogens or the prevalence of TMP-SMX resistance exceeded 17%. On 2-way sensitivity analysis, variables that had a significant impact on our cost-minimization threshold included cost of antibiotics and probability of clinical cure with antibiotics. CONCLUSION: From a payer perspective, nitrofurantoin appears to be a reasonable alternative to TMP-SMX and fluoroquinolones for empirical treatment of uncomplicated UTIs, especially given the current prevalence of antibiotic resistance among community uropathogens. On the basis of efficacy, cost, and low impact on promoting antimicrobial resistance, clinicians should consider nitrofurantoin as a reasonable alternative to TMP-SMX and fluoroquinolones for first-line therapy for uncomplicated UTIs.