Leishmaniasis cutánea resistente al antimoniato de meglumina intramuscular / Resistance to Intramuscular Meglumine Antimoniate in Cutaneous Leishmaniasis

La leishmaniasis es una enfermedad causada por pará- sitos protozoarios del género Leishmania. Se clasifica como: cutánea, mucocutánea y visceral. De las ante- riores, la Leishmaniasis cutánea (LC) es la forma más común a nivel mundial, transmitida a humanos por la picadura del mosquito hembra, el cual pertenece a la familia Phlebotominae y Lutzomyia. La cutánea gene- ralmente se manifiesta clínicamente por presentar una pápula ulcerada con exudado seroso, con fondo limpio de aspecto granular y bordes hiperémicos y engrosados. Presentamos el caso de un adolescente de 16 años de edad, procedente de Aldea Peña Blanca Norte, San Pe- dro Sula, con lesión eritemato-costrosa, tumefacta no dolorosa de 2 meses de evolución, en pabellón auri- cular derecho. El paciente fue visto en consulta exter- na de Dermatología Pediátrica del Instituto Hondure- ño de Seguridad Social Regional del Norte (I.H.S.S.), recibiendo tratamiento con antibióticos sistémicos y tópicos (trimetoprim sulfametoxazol, mupirocina un- güento), por 7 días. Previamente había recibido varios tratamientos sistémicos orales y parenterales (amoxici- lina/ ácido clavulánico, dicloxacilina, penicilina benza- tínica, y aplicación tópica de ácido fusídico) sin obtener mejoría clínica alguna; se le envió a realizar microsco- pía directa con tinción de Giemsa de frotis obtenido de la lesión en el Centro de Salud "Miguel Paz Barahona", demostrando la presencia de amastigotes. Se inició al antimoniato de meglumina según esquema estableci- do por la Organización Mundial de la Salud (OMS) a razón de 20 mg/kg/día intramuscular por 30 días. Debido a la falla de tratamiento se deci- de utilizar itraconazol durante 3 meses con buena respuesta y sin efectos adversos...(AU)

Early oral stepdown antibiotic therapy versus continuing intravenous therapy for uncomplicated Gram-negative bacteraemia (the INVEST trial): study protocol for a multicentre, randomised controlled, open-label, phase III, non-inferiority trial.

BACKGROUND: The incidence of Gram-negative bacteraemia is rising globally and remains a major cause of morbidity and mortality. The majority of patients with Gram-negative bacteraemia initially receive intravenous (IV) antibiotic therapy. However, it remains unclear whether patients can step down to oral antibiotics after appropriate clinical response has been observed without compromising outcomes. Compared with IV therapy, oral therapy eliminates the risk of catheter-associated adverse events, enhances patient quality of life and reduces healthcare costs. As current management of Gram-negative bacteraemia entails a duration of IV therapy with limited evidence to guide oral conversion, we aim to evaluate the clinical efficacy and economic impact of early stepdown to oral antibiotics. METHODS: This is an international, multicentre, randomised controlled, open-label, phase III, non-inferiority trial. To be eligible, adult participants must be clinically stable / non-critically ill inpatients with uncomplicated Gram-negative bacteraemia. Randomisation to the intervention or standard arms will be performed with 1:1 allocation ratio. Participants randomised to the intervention arm (within 72 h from index blood culture collection) will be immediately switched to an oral fluoroquinolone or trimethoprim-sulfamethoxazole. Participants randomised to the standard arm will continue to receive IV therapy for at least 24 h post-randomisation before clinical re-assessment and decision-making by the treating doctor. The recommended treatment duration is 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days if clinically indicated. Primary outcome is 30-day all-cause mortality, and the key secondary outcome is health economic evaluation, including estimation of total healthcare cost as well as assessment of patient quality of life and number of quality-adjusted life years saved. Assuming a 30-day mortality of 8% in the standard and intervention arms, with 6% non-inferiority margin, the target sample size is 720 participants which provides 80% power with a one-sided 0.025 α-level after adjustment for 5% drop-out. DISCUSSION: A finding of non-inferiority in efficacy of oral fluoroquinolones or trimethoprim-sulfamethoxazole versus IV standard of care antibiotics may hypothetically translate to wider adoption of a more cost-effective treatment strategy with better quality of life outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05199324 . Registered 20 January 2022.

Addressing the drug-resistant tuberculosis challenge through implementing a mixed model of care in Uganda.

Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and human immunodeficiency virus (HIV) status), on co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) statuses, culture results, smear results and treatment outcomes (6, 12, and 24 months) from 2012 to 2017 RR-TB/MDR-TB cohorts were collected from all the 15 DR-TB treatment initiation sites and descriptive analysis was done using STATA version 14.2. We presented outcomes as the number of patient backlog cleared, DR-TB initiation sites, RR-TB/DR-TB cumulative patients enrolled, percentage of co-infected patients on the six, twelve interim and 24 months treatment outcomes as per the Uganda NTLP 2016 Programmatic Management of drug-resistant Tuberculosis (PMDT) guidelines (NTLP, 2016). Over the period 2013-2015, the RR-TB/MDR-TB Treatment success rate (TSR) was sustained between 70.1% and 74.1%, a performance that is well above the global TSR average rate of 50%. Additionally, the cure rate increased from 48.8% to 66.8% (P = 0.03). The Uganda DR-TB mixed model of care coupled with early application of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges.

Emergency department medication dispensing reduces return visits and admissions.

OBJECTIVES: Return visits to the emergency department (ED) and subsequent readmissions are common for patients who are unable to fill their prescriptions. We sought to determine if dispensing medications to patients in an ED was a cost-effective way to decrease return ED visits and hospital admissions for skin and soft tissue infections (SSTIs). METHODS: A retrospective review of ED visits for SSTIs, during the 24 weeks before and after the implementation of a medication dispensing program, was conducted. Charts were analyzed for both ED return visits and hospital admissions within 7 days and 30 days of the initial ED visit. Return visits were further reviewed to determine if the clinical conditions on subsequent visits were related to the initial ED presentation. A cost analysis comparing the cost of treatment to cost savings for return visits was also performed. RESULTS: Before the implementation of the medication dispensing program, the return rate in 7 days for the same condition was 9.1% and the rate of admission was 2.8%. The return rate for the same condition in 8-30 days was 2.1% and the rate of admission was 1.0%. After the implementation of the medication dispensing program, the return rate for the same condition in 7 days was 8.0%, and the admission rate was 1.7%. The return rate for the same condition in 8-30 days was 0.8%, and the admission rate was 0%. The total cost of dispensed medications was $4050, while total cost savings were estimated to be $95,477. CONCLUSION: A medication dispensing program in the ED led to a reduction in return visits and admissions for SSTIs at both 7 days and 30 days. For a cost of only $4050, an estimated total of $95,477 was saved. A medication dispensing program is a cost-effective way to reduce return visits to the ED and subsequent admissions for certain conditions.

Informe diário de evidências COVID-19: busca realizada em 11 de agosto de 2020 / COVID-19 daily evidence report: search conducted on August 11, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 5 protocolos.

Prevalence and Clinical Management of Non-malarial Febrile Illnesses among Outpatients in the Era of Universal Malaria Testing in Malawi.

Increasing access to rapid diagnostic tests for malaria (mRDTs) has raised awareness of the challenges healthcare workers face in managing non-malarial febrile illnesses (NMFIs). We examined NMFI prevalence, clinical diagnoses, and prescribing practices in outpatient clinics across different malaria transmission settings in Malawi. Standardized facility-based malaria surveillance was conducted at three facilities one of every 4 weeks over 2 years. Information on demographics, presenting symptoms, temperature, clinical diagnosis, and treatment were collected from outpatients presenting with malaria-like symptoms. Of the 25,486 patients with fever, 69% had NMFI. Non-malarial febrile illness prevalence was lower in 5- to 15-year-old patients (55%) than in children < 5 years (72%) and adults > 15 years of age (77%). The most common clinical diagnoses among febrile patients with negative mRDTs in all age-groups and settings were respiratory infections (46%), sepsis (29%), gastroenteritis (13%), musculoskeletal pain (9%), and malaria (5%). Antibiotic prescribing was high in all age-groups and settings. Trimethoprim-sulfamethoxazole (40%) and amoxicillin (29%) were the most commonly prescribed antibiotics and were used for nearly all clinical diagnoses. In these settings with minimal access to diagnostic tools, patients with fever and a negative mRDT received a limited number of clinical diagnoses. Many were likely to be inaccurate and were associated with the inappropriate use of the limited range of available antibiotics. Prescription and diagnostic practices for NMFIs in the facilities require research and policy input. Resource-limited malaria-endemic countries urgently need more point-of-care diagnostic tools and evidence-based diagnosis and treatment algorithms to provide effective and cost-efficient care.

Use of antibacterials in the management of symptoms of acute respiratory tract infections among children under five years in Gulu, northern Uganda: Prevalence and determinants.

Inappropriate use of antibacterials is a major public health challenge as it can promote emergence of resistance, wastage of financial resources, morbidity and mortality. In this study, we determined the prevalence and factors associated with antibacterial use in managing symptoms of acute respiratory tract infections (ARIs) in households in rural communities of Gulu district, northern Uganda. A cross-sectional study was conducted among households selected using multi-stage sampling. Data were collected through interviews with care-givers of children under five years, using a structured interviewer administered questionnaire. Out of the 856 children who had symptoms of ARIs, 515 (60.2%; CI: 54.5%-65.6%) were treated with antibacterials. The most commonly used antibacterials were amoxicillin (55.2%, n = 358), cotrimoxazole (15.4%, n = 100) and metronidazole (11.4%, n = 74). The determinants of antibacterial use included; getting treatment from a health facility (AOR: 1.85, CI: 1.34-2.56, P < 0.001), households located in peri-urban area (AOR: 2.54, CI: 1.34-4.84, P = 0.005), and a child having cough (AOR: 7.02, CI: 4.36-11.31, P < 0.001). The prevalence of antibacterial use among children under five years with symptoms of ARIs is high in communities of Gulu district, northern Uganda. Getting treatment from a health facility, if a household was located in a peri-urban area and having a cough are positive predictors of antibacterial use. There is need for targeted education on appropriate antibacterial use in rural communities and hospital settings where over prescription is most likely especially in treating symptoms of ARIs among children under five years.

Access to prevention of mother-to-child transmission of HIV along HIV services cascade through integrated active case management in 15 operational districts in Cambodia.

INTRODUCTION: Following the introduction of option B+ in 2013, and with the perspective of eliminating mother-to-child transmission of HIV by 2025, Cambodia has implemented an integrated active case management (IACM) approach since 2014 to improve the notification and follow-up of all HIV-infected cases including pregnant women, and to ensure access to and use of the full prevention of mother-to-child transmission (PMTCT) service package by HIV-infected pregnant women and their HIV-exposed infants. This study aimed to analyse PMTCT cascade data in 15 operational districts (ODs) implementing the IACM approach in Cambodia. METHODS: We analysed PMTCT cohort data from 15 ODs implementing IACM approach between 1 January 2014 and 31 December 2016. We measured key indicators along the PMTCT cascade and compared them to available (cross-sectional) PMTCT indicators during the 2011 to 2013 period. RESULTS: During the period 2014 to 2016, among 938 identified HIV-infected pregnant women, 308 (32.8%) were tested HIV positive during their pregnancy, 9 (1.0%) during labour, while the remaining 621 (66.2%) were women on antiretroviral therapy (ART) who became pregnant. During the study period, 867 (92.4%) of the 938 women received ART during pregnancy and labour. Subsequently, 456 (85.6%) of the 533 HEI born and alive during the study period received 6-week antiretroviral (ARV) prophylaxis, 390 (76.6%) and 396 (77.8%) of the 509 infants aged six weeks or older received cotrimoxazole prophylaxis and HIV-DNA PCR test respectively. Among the 396 HEI who received HIV-DNA PCR test, 7 (1.8%) were found HIV positive. The comparison with cross-sectional PMTCT indicator obtained during the previous 2011 to 2013 period in the same 15 ODs, showed a significant increase in ARV uptake among HIV-infected pregnant women (from 72.3% to 92.4%), in cotrimoxazole uptake (from 41.6% to 73.2%), and in HIV-DNA PCR testing coverage among HEI (from 41.2% to 74.3%). CONCLUSIONS: The implementation of option B+ and IACM may have contributed to the improvement of the PMTCT cascade in Cambodia. However, some gaps in accessing PMTCT services along the HIV cascade persist and need to be addressed.

Achieving sustainable development goals for HIV/AIDS in the Republic of the Congo - Progress, obstacles and challenges in HIV/AIDS health services.

The HIV epidemic continues to be a major global public health issue. Since 2012, there has been a paucity of information from the Republic of the Congo on HIV incidence and prevalence rates, national HIV programme effectiveness, highly active antiretroviral therapy (HAART) rollout, patient adherence to treatment, operational and basic science research studies on HIV/AIDS, and donor funding and its impact on the country. A review of the existing literature on HIV in the Republic of the Congo was conducted, focused on prevalence trends, effectiveness of the current national HIV programme, HAART rollout, patient adherence to antiretrovirals (ARVs), resistance to ARVs, the cost of treatment, and operational issues affecting HIV/AIDS programmes in the country. In light of the findings, several important priority areas for scaling-up HIV/AIDS services, programmatic and research activities in the Republic of the Congo are highlighted.

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.

Drug Susceptibility Assessment in Stenotrophomonas Maltophilia Strains Isolated From the Blood of Organ Transplantation Recipients in a Warsaw Teaching Hospital During 2011 to 2014.

BACKGROUND: Blood infections with multidrug-resistant Gram-negative carbapenem-resistant bacilli are particularly dangerous and challenging to treat in organ transplant recipients. Resistance to carbapenems may be acquired, for example, in Enterobacteriaceae, Pseudomonas, or Acinetobacter spp. or innate, for example, in Stenotrophomonas maltophilia. The purpose of this study was to analyze blood infections caused by S maltophilia in organ transplant recipients and to compare drug susceptibility of these bacteria and the same species isolated from the blood of other inpatients. METHODS: A total of 26 S maltophilia strains isolated from blood samples of 26 patients (including 14 liver or kidney transplant recipients) hospitalized during 2011 to 2014 were evaluated in this study. Antibiotic susceptibility was determined via E-test and disk diffusion methods. RESULTS: Stenotrophomonas maltophilia strains isolated from blood exhibited sensitivity to trimethoprim/sulfamethoxazole (100%), levofloxacin (96.2%), ciprofloxacin (92.3%), ticarcillin/clavulanic acid (80.8%), and ceftazidime (53.9%). CONCLUSIONS: Because appropriate antibiotic therapy in the case of S maltophilia differs from the standard empirical therapy administered in the case of most other Gram-negative bacilli, early identification of this pathogen is of particular significance. The use of antibiotics to which this pathogen is sensitive eliminates the infection and helps avoid graft loss.

Adherence to European Association of Urology Guidelines on Prophylactic Antibiotics: An Important Step in Antimicrobial Stewardship.

BACKGROUND: The evolution of resistant pathogens is a worldwide health crisis and adherence to European Association of Urology (EAU) guidelines on antibiotic prophylaxis may be an important way to improve antibiotic stewardship and reduce patient harm and costs. OBJECTIVE: To evaluate the prevalence of antibiotic-resistant bacterial strains and health care costs during a period of adherence to EAU guidelines in a tertiary referral urologic institution. DESIGN, SETTING, AND PARTICIPANTS: A protocol for adherence to EAU guidelines for antibiotic prophylaxis for all urologic procedures was introduced in January 2011. Data for 3529 urologic procedures performed between January 2011 and December 2013 after protocol introduction were compared with data for 2619 procedures performed between January 2008 and December 2010 before protocol implementation. The prevalence of bacterial resistance and health care costs were compared between the two periods. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome measures were the proportion of resistant uropathogens and costs related to antibiotic consumption and symptomatic postoperative infection. We used χ2 and Fisher's exact tests to test the significance of differences. RESULTS AND LIMITATIONS: The proportion of patients with symptomatic postoperative infection did not differ (180/3529 [5.1%] vs. 117/2619 [4.5%]; p=0.27). A total of 342 isolates from all patients with symptomatic postoperative infections were analysed. The rate of resistance of Escherichia coli to piperacillin/tazobactam (9.1% vs. 5.4%; p=0.03), gentamicin (18.3% vs. 11.2%; p=0.02), and ciprofloxacin (32.3% vs. 19.1%; p=0.03) decreased significantly after protocol introduction. The defined daily dose (DDD) use of ciprofloxacin fell from 4.2 to 0.2 DDD per 100 patient-days after implementation (p<0.001). Antibiotic drug costs (€76,980 vs. €36,700) and costs related to postoperative infections (€45,870 vs. €29,560) decreased following introduction of the protocol (p<0.001). CONCLUSIONS: Adherence to EAU guidelines on antibiotic prophylaxis reduced antibiotic usage without increasing post-operative infection rate and lowered the prevalence of resistant uropathogens. PATIENT SUMMARY: We analysed the impact of adherence to European Association of Urology guidelines on antibiotic prophylaxis for all surgical urologic procedures on the prevalence of infections and resistant bacterial strains and on costs. We found that adherence to the guidelines reduced the rate of bacterial resistance, in particular against piperacillin/tazobactam, gentamicin, and ciprofloxacin, and reduced costs without increasing the risk of postoperative infection after urologic procedures. We recommend adherence to the guidelines as an important part of antibiotic stewardship programmes.

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.

Factors associated with access to HIV care services in eastern Uganda: the Kumi home based HIV counseling and testing program experience.

BACKGROUND: The HIV/AIDS health challenge continues to ravage many resource-constrained countries of the world. Approximately 75 % of all the global HIV/AIDS related deaths totaling 1.6 (1.4-1.9) million in 2012 occurred in sub-Saharan Africa, Uganda contributed 63,000 (52,000-81,000) to these deaths. Most of the morbidity and mortality associated with HIV/AIDS can be averted if individuals with HIV/AIDS have improved access to HIV care and treatment. The aim of this study therefore, was to explore the factors associated with access to HIV care services among HIV seropositive clients identified by a home based HIV counseling and testing program in Kumi district, eastern Uganda. METHODS: In a cross sectional study conducted in February 2009, we explored predictor variables: socio-demographics, health facility and community factors related to access to HIV care and treatment. The main outcome measure was reported receipt of cotrimoxazole for prophylaxis. RESULTS: The majority [81.1 % (284/350)] of respondents received cotrimoxazole prophylaxis (indicating access to HIV care). The main factors associated with access to HIV care include; age 25-34 years (AOR = 5.1, 95 % CI: 1.5-17.1), male sex (AOR = 2.3, 95 % CI: 1.2-4.4), urban residence (AOR = 2.5, CI: 1.1-5.9) and lack of family support (AOR = 0.5, CI: 0.2-0.9). CONCLUSIONS: There was relatively high access to HIV care and treatment services at health facilities for HIV positive clients referred from the Kumi home based HIV counseling and testing program. The factors associated with access to HIV care services include; age group, sex, residence and having a supportive family. Stakeholders involved in providing HIV care and treatment services in similar settings should therefore consider these socio-demographic variables as they formulate interventions to improve access to HIV care services.

Assessment of the impact of cotrimoxazole prophylaxis on key outcomes among HIV-infected adults in low- and middle-income countries: a systematic review.

BACKGROUND: Cotrimoxazole (CTX) prophylaxis is among the key interventions provided to HIV-infected individuals in resource-limited settings. We conducted a systematic review of the available evidence. METHODS: MEDLINE, Embase, Global Health, CINAHL, SOCA, and African Index Medicus (AIM) were used to identify articles relevant to the CTX prophylaxis intervention from 1995 to 2014. Included articles addressed impact of CTX prophylaxis on the outcomes of mortality, morbidity, retention in care, quality of life, and/or prevention of ongoing HIV transmission. We rated the quality of evidence in individual articles and assessed the overall quality of the body of evidence, the expected impact, and the cost effectiveness (CE) for each outcome. RESULTS: Of the initial 1418 identified articles, 42 met all inclusion criteria. These included 9 randomized controlled trials, 26 observational studies, 2 systematic reviews with meta-analysis, 1 other systematic review, and 4 CE studies. The overall quality of evidence was rated as "good" and the expected impact "high" for both mortality and morbidity. The overall quality of evidence from the 4 studies addressing retention in care was rated as "poor," and the expected impact on retention was rated as "uncertain." The 4 assessed CE studies showed that provision of CTX prophylaxis is cost effective and sometimes cost saving. No studies addressed impact on quality of life or HIV transmission. CONCLUSIONS: CTX prophylaxis is a cost-effective intervention with expected high impact on morbidity and mortality reduction in HIV-infected adults in resource-limited settings. Benefits are seen in both pre-antiretroviral therapy and antiretroviral therapy populations.