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.

Co-trimoxazole prophylaxis in adults, including pregnant women, with HIV: a systematic review and meta-analysis.

INTRODUCTION: Co-trimoxazole prophylaxis is used to reduce morbidity and mortality in people with HIV. We systematically reviewed three topics related to co-trimoxazole prophylaxis to update WHO guidelines: initiation, discontinuation, and dose. METHODS: We searched PubMed, Embase, WHO Global Index Medicus, and clinical trial registries in November, 2013, for randomised controlled trials and observational studies including co-trimoxazole prophylaxis and a comparator group. Studies were eligible if they reported death, WHO clinical stage 3 or 4 events, admittance to hospital, severe bacterial infections, tuberculosis, pneumonia, diarrhoea, malaria, or treatment-limiting adverse events. Infant mortality, low birthweight, and placental malaria were additional outcomes for the comparison of co-trimoxazole prophylaxis and intermittent preventive treatment for malaria in pregnant women (IPTp). We compared a dose of 480 mg co-trimoxazole once a day with one of 960 mg co-trimoxazole once a day. We used a 10% margin for non-inferiority and equivalence analyses. We used random-effects models for all meta-analyses. This study is registered with PROSPERO, number CRD42014007163. FINDINGS: 19 articles, published from 1995 to 2014 and including 35 328 participants, met the inclusion criteria. Co-trimoxazole prophylaxis reduced rates of death (hazard ratio [HR] 0·40, 95% CI 0·26-0·64) when started at CD4 counts of 350 cells per µL or lower with antiretroviral therapy (ART) worldwide. Co-trimoxazole prophylaxis started at higher than 350 cells per µL without ART reduced rates of death (0·50, 0·30-0·83) and malaria (0·25, 0·10-0·57) in Africa. Co-trimoxazole prophylaxis was non-inferior to IPTp with respect to infant mortality (risk difference [RD] -0·05, 95% CI -0·12 to 0·02), low birthweight (0·00, -0·07 to 0·07), and placental malaria (0·00, -0·10 to 0·10). Co-trimoxazole prophylaxis continuation after ART-induced recovery with CD4 counts higher than 350 cells per µL reduced admittances to hospital (HR 0·42, 95% CI 0·22-0·80), pneumonia (0·73, 0·61-0·88), malaria (0·03, 0·01-0·10), and diarrhoea (0·61, 0·48-0·78) in Africa. A dose of 480 mg co-trimoxazole prophylaxis once a day did not reduce treatment-limiting adverse events compared with 960 mg once a day (RD -0·07, 95% CI -0·52 to 0·39). INTERPRETATION: Co-trimoxazole prophylaxis should be given with ART in people with CD4 counts of 350 cells per µL or lower in low-income and middle-income countries. Co-trimoxazole prophylaxis should be provided irrespective of CD4 count in settings with a high burden of infectious diseases. Pregnant women with HIV in Africa should use co-trimoxazole rather than IPTp to prevent malaria complications in infants. Further research is needed to inform dose optimisation and co-trimoxazole use in the context of expanded ART in different epidemiological settings. FUNDING: None.

Outcome assessment in cellulitis clinical trials: is telephone follow up sufficient?

The US Food and Drug Administration has scrutinized clinical trial methodology in cellulitis, partly because the definition and timing of cure are debatable. We analysed the validity of telephone self-report as a proxy for in-person follow up in a cellulitis treatment trial comparing cephalexin alone with cephalexin-plus-trimethoprim/sulfamethoxazole. Our results demonstrate poor agreement between these two methods of outcome determination and have implications for future cellulitis clinical trial design and clinical management.

Alternative treatment approach to cerebral toxoplasmosis in HIV/AIDS: experience from a resource-poor setting.

The current standard treatment for cerebral toxoplasmosis (pyrimethamine/sulfadiazine) often encounters problems of poor tolerability, adverse effects, frequent dropouts and non-availability of pyrimethamine/sulfadiazine in some parts of India. We have had to use the combination of two effective alternative agents for toxoplasmosis, cotrimoxazole and clindamycin, on compassionate grounds. This retrospective observational study reports superior efficacy and better tolerability of cotrimoxazole/clindamycin compared to the recommended regimen. Primary end-point (complete response) was defined as more than 50% improvement of clinical status or more than 50% decrease in the size of brain lesions after two weeks of treatment initiation. Complete response occurred more commonly with cotrimoxazole/clindamycin than with pyrimethamine/sulfadiazine group (80% vs. 31.25%, respectively, relative risk 2.56, 95% confidence interval: 1.21-5.43). There was a trend towards higher on-treatment mortality in the pyrimethamine/sulfadiazine group in comparison to the cotrimoxazole/clindamycin (mortality rate 37.5% in pyrimethamine/sulfadiazine vs 12% in cotrimoxazole/clindamycin, p = 0.07, relative risk = 3.125, 95% confidence interval: 0.91-10.75). Overall, 62.5% (10/16) of patients on pyrimethamine/sulfadiazine suffered drug-related adverse reactions compared to 24% (6/25) on cotrimoxazole/clindamycin (p = 0.02, relative risk = 2.60, 95% confidence interval: 1.17-5.76). The commonest complication of pyrimethamine/sulfadiazine was severe thrombocytopenia with major bleeding (4/16, 25%). We propose that the new combination chemotherapy, which is widely available, effective and safe, can be used in developing countries.

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.

Delivering TB/HIV services in Ghana: a comparative study of service delivery models.

BACKGROUND: TB and HIV interaction increases TB incidence and HIV adverse outcomes. Integration improves patients' access to comprehensive care. This paper compares the impact of increasing integration on TB/HIV service delivery. METHODS: Three hospitals with different delivery models were identified and a survey of TB cases registered between June 2007 and December 2008 conducted. HIV screening, co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) uptake for HIV-positive TB patients were compared. RESULTS: Of the 590 TB patients, 85.9% (507/590) knew their HIV status. HIV screening was highest (98.6% [95%CI: 97.6-99.5%]) at the one-stop shop (OSS) and lowest (72.5% [71.9-73.9%]) at the referral site (RS). CPT was highest [(93.8% [91.0-96.7%]) at the RS and least (74.7% [72.8-76.5%]) at the partially-integrated site (PIS). At the OSS it was 82.3% (80.6-84.0%). ART was highest (59.5% [58.0-61.0%]) at the PIS, and 10.8% (10.4-11.1%) at the RS. No ART records existed at the OSS. CONCLUSIONS: Increasing integration improved HIV screening but not CPT or ART uptake. There was insufficient evidence to identify the most effective model due to design limitations and health system barriers. More research and training is needed to improve uptake, data completeness and accuracy.

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.

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.

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.

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.

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.

When to start antiretroviral therapy in resource-limited settings.

BACKGROUND: The results of international clinical trials that are assessing when to initiate antiretroviral therapy (ART) will not be available for several years. OBJECTIVE: To inform HIV treatment decisions about the optimal CD4 threshold at which to initiate ART in South Africa while awaiting the results of these trials. DESIGN: Cost-effectiveness analysis by using a computer simulation model of HIV disease. DATA SOURCES: Published data from randomized trials and observational cohorts in South Africa. TARGET POPULATION: HIV-infected patients in South Africa. TIME HORIZON: 5-year and lifetime. PERSPECTIVE: Modified societal. INTERVENTION: No treatment, ART initiated at a CD4 count less than 0.250 x 10(9) cells/L, and ART initiated at a CD4 count less than 0.350 x 10(9) cells/L. OUTCOME MEASURES: Morbidity, mortality, life expectancy, medical costs, and cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: If 10% to 100% of HIV-infected patients are identified and linked to care, a CD4 count threshold for ART initiation of 0.350 x 10(9) cells/L would reduce severe opportunistic diseases by 22,000 to 221,000 and deaths by 25,000 to 253,000 during the next 5 years compared with ART initiation at 0.250 x 10(9) cells/L; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART initiation strategy would increase long-term survival by at least 7.9 years, with a mean per-person life expectancy of 3.8 years with no ART and 12.5 years with an initiation threshold of 0.350 x 10(9) cells/L. Compared with an initiation threshold of 0.250 x 10(9) cells/L, a threshold of 0.350 x 10(9) cells/L has an incremental cost-effectiveness ratio of $1200 per year of life saved. RESULTS OF SENSITIVITY ANALYSIS: Initiating ART at a CD4 count less than 0.350 x 10(9) cells/L would remain cost-effective over the next 5 years even if the probability that the trial would demonstrate the superiority of earlier therapy is as low as 17%. LIMITATION: This model does not consider the possible benefits of initiating ART at a CD4 count greater than 0.350 x 10(9) cells/L or of reduced HIV transmission. CONCLUSION: Earlier initiation of ART in South Africa will probably reduce morbidity and mortality, improve long-term survival, and be cost-effective. While awaiting trial results, treatment guidelines should be liberalized to allow initiation at CD4 counts less than 0.350 x 10(9) cells/L, earlier than is currently recommended. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases and the Doris Duke Charitable Foundation.

Management of neurobrucellosis: an assessment of 11 cases.

OBJECTIVE: The central nervous system involvement of Brucellosis causes a hard to treat infection with multiple sequelae. The aim of this paper is to discuss the course of neurobrucellosis in response to therapy. PATIENTS AND METHODS: Patients with neurobrucellosis were evaluated. The diagnosis was established by the isolation of bacteria, abnormal CSF findings and positive serology. Ceftriaxone, rifampicin, doxycycline and trimethoprim sulfamethoxazole were the antibiotic choices for these cases. RESULTS: We present 11 cases with neurobrucellosis. None of our patients died, albeit one case has a critical situation due to subarachnoid hemorrhage and its' concordant sequelae. Only one of four patients with walking difficulty and two with hearing loss were normalized with therapy. Imaging techniques did not provide any specific contribution regarding the Brucella infection. CONCLUSIONS: Parenteral ceftriaxone should be used as an initial alternative in the management of neurobrucellosis. Although the therapy should be individualized, the duration of therapy should be a minimum of six months with suitable antibiotics.

[The first case of single pancreas transplantation in Hungary]. / Szoliter hasnyálmirigy-átültetés elsô esete Magyarországon.

UNLABELLED: Simultaneous pancreas kidney (SPK) transplantation is the only routinely used therapeutic option which can provide insulin independence, euglycemia and good renal replacement for type I diabetes mellitus patients with end stage renal disease. Several patients have some complications of diabetes without renal failure. For these patients pancreas transplantation alone is a therapeutic option. The first pancreas transplantation alone was performed 6 years after the launch of our pancreas transplant program. The patient was a 40-years-old man. Enteric drainage was used with portal venous drainage. Anti IL-2. R antibody, daclizumab was given as prolonged induction therapy. In spite of the technical and immunological difficulties there were neither technical failures nor acute rejection. 3 years after the transplantation the patient has a good quality of life without insulin therapy with excellent renal function. CONCLUSION: PTA transplant is a routinely used therapeutic option with good survival rate and good quality of life for type I diabetes mellitus patients without end stage renal disease.

Occurrence and determinants of trimethoprim/sulfamethoxazole use in pregnancy.

OBJECTIVE: To estimate the rate of prescription trimethoprim/sulfamethoxazole use in pregnancy, and to analyse the association between maternal characteristics and use of trimethoprim/sulfamethoxazole in pregnancy. METHODS: A population-based study was conducted based on a 50% random sample of women who gave a birth in Saskatchewan between 1 January 1997 and 31 December 2000. The rate of trimethoprim/sulfamethoxazole use during pregnancy was estimated. The exposure in each trimester was also estimated. Associations between maternal characteristics and pregnancy trimethoprim/sulfamethoxazole use were evaluated using multiple logistical regression with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) as the association measures. RESULTS: A total of 18,575 women who gave a birth in Saskatchewan during the study period were included in the analysis. Among them, 596 (3.2%) had at least 1 prescription for trimethoprim/sulfamethoxazole during pregnancy, 389 (2.1%) in the first trimester, 208 (1.1%) in the second trimester, and 195 (1.1%) in the third trimester. Women with chronic health conditions (6.2%) had a 2-fold increased risk of exposure compared to women without a chronic health condition (2.8%). Younger women (<20 years) with parity >/=3 and women on Saskatchewan assistance plan were also at increased risk. There were variations in exposure by trimester. For example, teenage women without chronic health conditions were at increased risk of use in the second and third trimester. CONCLUSIONS: Some 3.2% of women are exposed to trimethoprim/sulfamethoxazole during pregnancy. Women with chronic health problems, of younger age, and of lower socioeconomic status are at elevated risk of exposure to trimethoprim/sulfamethoxazole during pregnancy.

[Cost-effectiveness of the treatment of acute and chronic rhinosinusitis at the IMSS]. / Costo-efectividad del tratamiento de rinosinusitis aguda y crónica en el IMSS.

INTRODUCTION: Rhinosinusitis is one of the more common diseases encountered in outpatient visits to health care. The objective of this study was to determine the most cost-effective antibiotic treatment for patients with acute (RSA) and chronic rhinosinusitis (RSC) that is available at the Mexican Institute of Social Security (IMSS). METHODS: Cost-effectiveness analysis of RSA and RSC treatment from an institutional perspective. Effectiveness outcome was defined as the percentage of cure. A decision tree with a Bayesian approach included the following therapeutic alternatives: ciprofloxacin, gatifloxacin, trimetoprim/sulfametoxazol (TMP/SMX), amoxicilin/clavulanic acid (AAC) and clindamicin. RESULTS: Treatment for RSA with AAC showed a mean cost per cured patient of $ 878 pesos. The remaining antibiotics had a higher cost per unit of success, and therefore the results showed that AAC was the best alternative considering this criterion. The therapy that showed a larger percentage of cured patients in RSC was clindamicin; however, the therapeutic alternative with the lowest cost per successful unit was the one based on ciprofloxacin, which dominates gatifloxacin and AAC. CONCLUSIONS: The most cost-effective alternative in the antibiotic treatment of patients with RSA was ACC while for RSC it was ciprofloxacin; sensitivity analysis showed the strength of the base study results.

Impact of antibiotic administrative restrictions on trends in antibiotic resistance.

CONTEXT: In March 2001, in response to concerns about increasing resistance to fluoroquinolone (FQ) antibiotics, the Ontario Drug Benefit (ODB) program limited reimbursement of FQs to ODB beneficiaries defined as high risk or in whom other therapies are not tolerated. OBJECTIVE: To analyze the impact of the limited use (LU) policy changes on antibiotic resistance rates in Ontario, focussing on community-acquired pathogens. DESIGN: Ontario data submitted to the Canadian Bacterial Surveillance Network (CBSN) between January 1, 1998 and June 30, 2002 were analyzed for rates of resistance in various pathogen-antibiotic combinations. The effect of the LU policy on the level and rate of change of antibiotic resistance was estimated using time series models. RESULTS: Resistance rates for S. pneumoniae were 10-12% for penicillin, erythromycin and trimethoprim sulfamethoxazole (TMP/SMX) and less than 3% for amoxicillin and all three FQs tested. There was a statistically significant increasing trend in resistance rates of S. pneumoniae to amoxicillin and levofloxacin throughout the study period. Antibiotic resistance of S. pneumoniae to ciprofloxacin indicated a statistically significant decreasing trend over the study period with a statistically significant increase in the level of antibiotic resistance at the time of the LU policy implementation. No other indication of any statistically significant decrease in resistance rates associated with the LU policy was found. CONCLUSIONS: Although no direct cause and effect can be proven with these observational data, there is no evidence that the limited use policy to restrict fluoroquinolones decreased antibiotic resistance in any of the pathogen-antibiotic combinations tested.