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This study aimed to assess the prevalence and reasons for nonadherence to cotrimoxazole prophylaxis therapy. A cross-sectional study was conducted among people living with HIV attending Ayder Comprehensive Specialized Hospital. Data were collected through interviews and reviews of medical records. Binary logistic regression was employed to analyze factors associated with CPT nonadherence. Approximately two-thirds (65.5%) of the participants were non-adherent to co-trimoxazole prophylaxis therapy. The main reasons for non-adherence were side effects, pill fatigue and forgetfulness. Strategies to improve adherence to co-trimoxazole prophylaxis therapy should focus on the combined patient, clinical and medication related issues of people living with HIV. [ABSTRACT FROM AUTHOR]

Background: Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii and is responsible for gestational and congenital infections worldwide. The current standard therapy is based on the administration of Spiramycin to prevent trans‐placental transmission. Other therapies are being studied to reduce the rates of foetal transmission and symptomatic congenital infection. Objectives: We report our long‐standing experience in maternal toxoplasmosis infection treatment using a combination of Spiramycin–Cotrimoxazole, assessing its effectiveness in preventing vertical transmission compared to the expected incidence of congenital infection. Methods: We retrospectively collected cases of pregnant women referred to our centre for suspected toxoplasmosis infection according to Lebech criteria, treated with Spiramycin–Cotrimoxazole. Results: Of 1364 women referred to our centre, postnatal follow‐up of primary toxoplasmosis was available in 562 cases (73.9%). The overall vertical transmission rate was 3.4% in women treated immediately with Spiramycin–Cotrimoxazole after the diagnosis of infection. In comparison, it was 7.7% in women undergoing the same therapy but late or with poor compliance. The foetal transmission rate was 71.4% in untreated cases. All the infected newborns of mother treated adequately with Spiramycin–Cotrimoxazole were asymptomatic afterbirth, while 6/21 infected infants of the inadequate Spiramycin–Cotrimoxazole therapy group had postnatal sequelae (28.5%). The incidence of transmission after appropriate Spiramycin–Cotrimoxazole therapy was significantly lower than the expected rate reported in literature. Conclusions: A combination of Spiramycin and Cotrimoxazole is safe and effective in preventing foetal congenital toxoplasmosis and reducing sequelae in case of in‐utero infection. The timing and adherence to the therapy are crucial to lowering the risk of congenital infection and neonatal morbidity. [ABSTRACT FROM AUTHOR]

Background: Existing literature has questioned the sensitivity of patch testing (PT) with cotrimoxazole (CTX) in the study of drug hypersensitivity. Objectives: Assess the sensitivity of PT with CTX in non‐immediate cutaneous adverse drug reactions (CADR). Patients/Materials/Methods: Retrospective analysis (2000–2022) of PT with an antibiotic series including CTX 10% pet (Chemotechnique Diagnostics©) performed according to ESCD guidelines in patients with suspected non‐immediate CADR reactions to CTX. Some patients were additionally tested with in‐house preparations of CTX from Bactrim DS® tablets at 10% in pet or water and trimethoprim 10% pet (Laboratórios Edol©). Results: Sixty‐four patients (48F/16M; mean age 47 ± 18) were included, mostly with maculopapular exanthema (51, 80%). Notably, CTX was sole suspect in 24 patients. There was no positive reaction to CTX at 10% from Chemotechnique or Bactrim DS® tablets prepared at 10% pet for patch testing. One patient reacted exclusively to trimethoprim with 1+ reaction. Two patients had a faint reaction (1+) only with the powder of Bactrim DS® tablets in water at D2, but as the reactions faded completely in 24 or 48 h, they were interpreted as irritant non‐specific reactions. Conclusion: These findings suggest that patch testing may lack sufficient sensitivity to diagnose CTX‐induced non‐immediate CADR. Therefore, clinicians should be cautious interpreting CTX patch test results. [ABSTRACT FROM AUTHOR]

Pneumocystis jirovecii pneumonia (PJP) is a potentially fatal type of pneumonitis, which may have devastating consequences. Typically, it occurs in immunocompromised patients, with the natural history varying depending on the presence or not of HIV infection. Staining and polymerase chain reaction (PCR) testing in induced sputum or bronchoalveolar lavage (BAL) is the cornerstone of the diagnosis, while trimethoprim-sulfamethoxazole is the treatment of choice. The etiological association of biologic agents with the occurrence of PJP is not entirely clear. Adalimumab is a fully human monoclonal anti-TNF-alpha antibody, which has been introduced relatively recently in the treatment of autoimmune inflammatory diseases, such as rheumatoid arthritis. In contrast to other biologic agents, such as Alemtuzumab or Infliximab, there are a small number of reports that support the drug's ability to trigger the occurrence of PJP. Hereby, we present a 53-year-old female patient with a medical history of rheumatoid arthritis on Adalimumab therapy, who developed PJP and we will discuss the main characteristics of PJP and the possible contribution of biologics to the occurrence of the infection. [ABSTRACT FROM AUTHOR]

Purpose: The recent restriction on the use of fluoroquinolones for prophylaxis by the European Commission has left a gap in clear recommendations for practical antibiotic prophylaxis (PAP) for transrectal prostate biopsy (TRPB). This analysis investigated the viability of cotrimoxazole for PAP in TRPB. Methods: This analysis included n = 697 patients who underwent TRPB for suspected prostate cancer (PCa). All patients received either empiric PAP with four doses of cotrimoxazole 960 mg or targeted antibiotic prophylaxis in case of a positive rectal or urine screening for multiresistant gram-negatives. Infectious complications after TRPB, microbiological findings, and clinical characteristics were evaluated. A multivariable logistic regression model was calculated to identify variables associated with infectious complications. Results: Of the cohort, 86% (600/697) received PAP with cotrimoxazole, 1% (8/697) received cotrimoxazole plus an additional antibiotic, 4% (28/697) received amoxicillin + clavulanic acid, 4% (28/697) received fluoroquinolones, and 5% (33/697) received a single shot intravenous antibiotic prophylaxis with meropenem or piperacillin + tazobactam due to multiresistant microbiological findings in either pre-interventional urine culture or rectal swab. Infectious complications occurred in 2.6% (18/697) of patients. Fever was noted in 89% (16/18) of cases. Inpatient treatment was given to 67% (12/18) of affected patients, with 38% (7/18) having positive blood cultures, identifying cotrimoxazole-resistant E. coli strains in six out of seven cases. Multivariable logistic regression analysis revealed no clinically significant variables, including PAP with cotrimoxazole, as independent risk factors for an infectious complication. Conclusions: Using cotrimoxazole as PAP for TRPB in cases without multiresistant gram-negatives in pre-interventional urine cultures or rectal swabs seems feasible and practical. [ABSTRACT FROM AUTHOR]

A sudden emergence of Stenotrophomonas maltophiliaas a primary pathogen both in immunocompromised and immunocompetent individuals has raised a serious concern, as it is associated with significant case fatality ratio. We intended to study the clinico-microbiological profile of S. maltophilia isolates from various samples and outcome of the infections in a tertiary healthcare center, Pune, India. This is an observational cross-sectional study was conducted from January 2021 to June 2022 at Department of Microbiology of a tertiary care Centre in Pune, India. Of the 12049 samples received for culture, S. maltophilia was isolated in 57 samples. Only 42 samples with pure growth of S. maltophilia were included in the study with 15 excluded due to mixed growth. All isolates were confirmed by VITEK-MS (bioMerieux, SA, France) which uses Matrix Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) technology. Of the 42 isolates, majority were isolated from pus(28.6%) and most of patients (61.9%) were from acute health care settings. The isolates had high susceptibility to Cotrimoxazole (85.7%) and Minocycline (85.7%) and low susceptibility to Ceftazidime (45.2%). A case fatality rate of 7.1% (3/42 cases) was noted and 39 cases were discharged after complete treatment. All the three fatal cases were susceptible to levofloxacin, ciprofloxacin, cotrimoxazole and minocycline and all three fatal cases were resistant to ceftazidime. S. maltophilia has recently shown an increase in nosocomial infections especially in acute healthcare settings like ICU and other critical care wards. The isolates of the present study had high susceptibility to trimethoprim-sulfamethoxazole (TMP-SXT) and Minocycline and low susceptible to Ceftazidime. [ABSTRACT FROM AUTHOR]

Introduction: Pneumocystis jirovecii pneumonia (PJP) is a severe, life-threatening complication in patients treated with rituximab. However, there is no consensus on the primary prophylaxis for it in rituximab-treated pemphigus patients. Therefore, we sought to investigate the prophylactic efficacy and safety profile of cotrimoxazole for reducing the risk of developing PJP in pemphigus patients receiving rituximab. Methods: This single-center retrospective study investigated 148 pemphigus patients undergoing a first cycle of rituximab between 2008 and 2021 at a tertiary referral center in northern Taiwan. Patients were divided into the prophylaxis group (N = 113) and the control group (N = 35) according to whether or not cotrimoxazole was administered. The primary outcome was the 1-year incidence of PJP in the two groups, while the secondary outcome was the incidence of cotrimoxazole-related adverse events. Results: Of the 148 patients enrolled in this study, three patients, all in the control group, developed PJP during the 1-year follow-up. The incidence of PJP (8.6%) in the control group was significantly higher than that in the prophylaxis group (0%) (p = 0.012). The incidence of cotrimoxazole-related adverse events was 2.7%, and none of the cases were associated with life-threatening conditions. In addition, the cumulative prednisolone dose was associated with a trend of a higher risk of PJP (p = 0.0483). Conclusions: Prophylactic cotrimoxazole significantly reduces the risk of PJP in a certain high-risk population and has a tolerable safety profile. [ABSTRACT FROM AUTHOR]

Stenotrophomonas maltophilia (S. maltophilia), an important pathogen in immuno-compromised patients, has recently gained attention in patients admitted in intensive care units (ICU). We sought to investigate clinical features of infections caused by S. maltophilia in ICU patients and identify risk factors for mortality. We conducted a retrospective study in two multivalent non-COVID-19 ICUs of tertiary-teaching hospitals in Greece and Spain, including patients with isolated S. maltophilia from at least one clinical specimen along with clinical signs of infection. A total of 103 patients (66% male) were analyzed. Median age was 65.5 (54–73.3) years and mean APACHE II and SOFA scores upon ICU admission were 18.36 (±7.22) and 18.17 (±6.95), respectively. Pneumonia was the predominant clinical syndrome (72.8%), while 22% of cases were among hemato/oncology patients. Crude 28-day mortality rate was 54.8%, even though, 14-day clinical and microbiological response was 96%. Age, APACHE II on ICU admission, hemato-oncologic disease, and multi-organ failure were initially identified as potential predictors of mortality. In the multivariable analysis, only increasing age and hemato-oncologic disease were shown to be independent risk factors for 28-day mortality. High all-cause mortality was observed in critically ill patients with predominantly respiratory infections by S. maltophilia, despite initial clinical and laboratory response after targeted treatment. The study elucidates a potentially worrisome emerging pathogen in the ICU. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the role of nasal Staphylococcus aureus (S. aureus) colonization and the effect of systemic or local antibiotic treatment on disease activity in patients with antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis and ear nose and throat (ENT) involvement. Clinical, laboratory and histological data from all patients with ANCA-associated vasculitis and ENT involvement, who were diagnosed in two medical centres in The Netherlands between 1981 and 2020, were retrospectively collected. Nasal S. aureus colonization was defined as at least one positive nasal swab during follow-up. Data on systemic (cotrimoxazole and azithromycin) and local (mupirocin) antibiotic use were collected. Disease activity was divided into systemic and local disease activity. Univariate analyses and regression analyses (negative binomial Poisson and binary regression) were used. Two-hundred and thirteen patients were available for analysis. Median follow-up time was 8 (IQR 3–17) years. S. aureus colonization was tested in 100 (46.9%) cases of whom 44 patients (44%) tested positive. In these 100 patients, systemic and local disease activity at baseline and at last visit were comparable between patients with and without S. aureus colonization. Twenty-eight of the 44 S. aureus positive patients received antibiotics aimed at eradication of S. aureus. No statistically significant difference was found between the treated versus non-treated group with regard to systemic and local disease activity. Nasal S. aureus colonization does not influence systemic or local disease activity. Antibiotic treatment aimed at eradication did not modify disease activity. [ABSTRACT FROM AUTHOR]

Sweet syndrome (SS) is an uncommon auto-inflammatory disorder presenting with acute pyrexia, leucocytosis and erythematous skin lesions with dense neutrophilic dermal infiltration. SS is seen as adverse reaction to some drugs, microbes and is associated with certain myeloproliferative or haematological neoplasms and is also seen with autoimmune diseases like inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, etc. A female aged 43 years, came to the hospital with high fever and erythematous, pus-filled plaques and nodules on her face, neck, shoulders and extremities, after taking cotrimoxazole (antibacterial agent) in tablet form 480 mg twice daily for five days for urinary tract infection. The diagnosis of SS was arrived upon from the biopsy reports showing predominant neutrophilic infiltrate, and relevant laboratory tests. Treatment included oral prednisone (corticosteroid) and the symptoms resolved in two months. [ABSTRACT FROM AUTHOR]

We followed 54 infants with in utero HIV after initiating very early antiretroviral treatment. At weeks 24 and 48, ≥80% had CD4 ≥1500 cells/mm3 and CD4% ≥25%. Routine Pneumocystis jirovecii pneumonia prophylaxis in the first year of life may not be necessary for all very early treated infants. Clinical Trials Registration NCT02140255. [ABSTRACT FROM AUTHOR]

A 34-year-old man who presents recurrent urological infections treated with different antibiotics as a consequence of urethral stricture, has undergone several surgeries since 2018. Some episodes of infection present with very intense pain and others are asymptomatic. In December 2021, high fever, very intense headache and muscle pain appeared for the first time, for which reason the symptoms were confused with COVID-19. When these symptoms appeared, the patient had been treated for 8 days with Trimethoprim/sulfamethoxazole 160/800 mg. After negative COVID-19 tests, they decide to hospitalize the patient in urology and determine that the symptoms are due to urological infection. He was also diagnosed with myocarditis and peripheral neuropathy. During the following months, the patient returns to have positive urine cultures for different bacteria and is treated with other antibiotics. In May 2022, after positive for Escherichia coli, he was prescribed Trimethoprim/sulfamethoxazole 160/800 mg, 2 days after starting treatment he was hospitalized with a very high fever, severe headache, and pain in the lower back and in the extremities that prevented him from moving. He is referred to traumatology and is diagnosed with low back pain. After the second admission, the patient discusses the case with his trusted pharmacist who knows his clinical history from the beginning and by conducting a study it is detected that there is a possibility that the acute symptoms are due to an adverse effect of trimethoprim/sulfamethoxazole 160/800 mg. The pharmacist notifies the patient of her suspicion that she transfers him to the doctors who treat him. Information on possible intolerance/allergy is included in the patient's clinical history. [ABSTRACT FROM AUTHOR]

Paracoccidioidomycosis (PCM), which mainly affects rural workers, is a systemic mycosis caused by the Paracoccidioides genus that induces pulmonary sequelae in most adult patients, causing serious disability and impairing their quality of life. Silymarin is herbal medicine with an effective antifibrotic activity. Considering that in PCM, antifibrotic treatment is still not available in pulmonary fibrosis, we aimed to evaluate combined silymarin and cotrimoxazole (CMX) therapy via the intratracheal route in BALB/c mice infected with P. brasiliensis yeast. After 12 weeks of treatment, the lungs were collected for the determination of fungal burden, production of OH-proline, deposition of collagen fibers, pulmonary concentrations of cytokines, and expression of fibronectin, α-SMA, MMP-2, MMP-9, and TIMP-2. Spleen cell cultures were also performed. Our results showed that infected mice treated with combined silymarin/CMX showed lower deposition of collagen fibers in the lungs and lower pulmonary concentrations of hydroxyproline than the placebo groups. Decreased levels of TGF-β1 and fibronectin and high levels of MMP-2 and IFN-γ were also observed in this group of mice. Collectively, our findings indicate that the combination of antifungal treatment with silymarin has a potent antifibrotic effect associated with an immunomodulatory effect that potentializes the antifungal immune response. [ABSTRACT FROM AUTHOR]

We present the case of a 55‐year‐old male patient who developed hyperkalemia after using Cotrimoxazole (TMP‐SMX). There was a marked increase in potassium levels from 3.3 mEq/L on Day 5 when cotrimoxazole was started to 6.2 mEq/L on Day 11 when the drug was withheld. [ABSTRACT FROM AUTHOR]

Childhood malnutrition affects physiology and development. It increases infection rates, which may not present clinical signs in severe cases. The World Health Organization recommends prophylactic treatment with cotrimoxazole (SXT) and nutritional recovery to overcome this issue. This treatment is controversial, since evidence of a reduction in morbidity and mortality is not a consensus and could induce the development of antibiotic-resistant bacteria. Moreover, the impact of using this wide-spectrum antibiotic on gut microbiota in a critical period of development, and weakness is unknown. To understand how SXT prophylaxis could affect gut microbiota in undernutrition, we induced protein–energy undernutrition (PEU) in weaning C57BL/6 mice for three weeks and treated animals with SXT for two weeks. Using 16S rRNA gene sequencing, we compared the taxonomic composition and metabolic pathways of control mice, animals submitted to undernutrition (UND), treated with SXT, or undernourished and SXT treated (UND + SXT). We identified that UND mice had a significant increase in predicted pathways related to metabolic syndromes later in life. The prophylactic SXT treatment alone resulted in a significant loss in community richness and beta diversity. Furthermore, we identified the reduction of three genera in SXT treated mice, including the butyrate producers Faecalibacterium and Anaerotruncus. Both UND and double challenge (UND + SXT) resulted in a reduction of the amino acid's biosynthesis pathway related to cell growth. Our results show that the SXT prophylaxis of young mice during an undernourishment period did not re-establish the undernourished microbiota community composition similar to healthy controls but induced a distinct dysbiotic profile with functional metabolic consequences. [ABSTRACT FROM AUTHOR]

Owing to a broad spectrum and low cost antimicrobial, cotrimoxazole is largely prescribed. However, its use is associated with various adverse drug reactions (ADRs) that warrant to ensure rational prescribing. This study aimed to describe spontaneous reports of cotrimoxazole ADRs and to evaluate the quality of prescription in patients who had ADRs. Suspected cotrimoxazole‐induced ADRs cases reported to the Bordeaux regional pharmacovigilance center (France) during a 5‐year period were described. Seriousness was assessed according to international criteria. Quality of prescription was assessed by compliance with the Summary of Product Characteristics (SPC) and relevance of cotrimoxazole indication. Then, an ADR was considered as preventable if the cotrimoxazole indication was not relevant, or potentially preventable if indication was relevant but the prescription was not compliant with the SPC. A total of 96 cases were analyzed: median age was 60.5 years (range: 4–94); 59.4% of patients were male. ADRs were mostly cutaneous disorders (n = 46) and hematological disorders (n = 25). A total of 60 serious ADRs occurred in 55 patients. Prescribers complied with all SPC recommendations in 21.9% of cases. Indication of cotrimoxazole was relevant or highly relevant in 41 cases. In 58% of cases, the occurrence of a cotrimoxazole‐induced ADR would have been preventable or potentially preventable. In a context of increasing interest for this antibiotic to treat infections due to resistant bacteria, physicians should be more aware of the potential consequences of inappropriate prescribing cotrimoxazole and reserve its use when there is no alternative and under suitable monitoring. [ABSTRACT FROM AUTHOR]

Objectives: At normal doses of trimethoprim-sulfamethoxazole (TMP/SMX), trimethoprim inhibits tubular creatinine secretion, leading to a rapid but reversible increase in serum creatinine (SCr). Although patients with connective tissue diseases are often in the state of immunosuppression and TMP/SMX is an important prophylactic drug, clinicians often have to stop or reduce the dosage due to concerns regarding its effect on renal function. This study aimed to evaluate the effect of a prophylactic dose of TMP/SMX on SCr in Japanese patients with connective tissue diseases, the extent of SCr level elevation and the independent risk factors for creatinine elevation. Methods: A retrospective cohort study was undertaken. Participants included patients with connective tissue diseases who were treated with a prophylactic dose of TMP/SMX between 2004 and 2018. Using single and multiple regression analyses, the risk factors that affected SCr elevation were evaluated. Results: A total of 262 patients, females, n = 181; age, median (range) = 59 (19-89) years, were included. The median baseline SCr level before treatment was 0.62 (0.16-2.1) mg/dL. The median SCr elevation value was 0.07 (−0.54 to 0.84) mg/dL in 4 weeks after TMP/SMX initiation. Five (2%) participants had ⩾0.3 mg/dL SCr elevation. Multiple regression analyses, including age, baseline SCr, diuretic use, nonsteroidal anti-inflammatory drug use and diabetes mellitus, indicated that baseline SCr and advanced age were independent risk factors of SCr elevation. Conclusions: These results demonstrated that baseline SCr and advanced age were associated with SCr elevation by a prophylactic dose of TMP/SMX. However, a prophylactic dose of TMP/SMX rarely elevated the SCr level significantly. Therefore, other causes can be considered if patients show an SCr elevation ⩾0.3 mg/dL. [ABSTRACT FROM AUTHOR]

Rituximab is widely used as the first‐line treatment for pemphigus patients. Since it depletes the B cells, it increases the risk of infections. Here, we evaluated the prophylactic efficacy of cotrimoxazole in decreasing the risk of pneumocystis pneumonia (PCP) infection in the pemphigus patients treated with rituximab. The medical records of confirmed pemphigus patients receiving rituximab were evaluated in two groups; those who received cotrimoxazole as a prophylactic after rituximab and patients who only received rituximab without any prophylaxis. The occurrence of PCP infection was determined in each group and compared. Medical records of 494 patients, including 301 women and 193 men, with the mean age of 46.74 years were analyzed. The phenotypes of the disease were mucocutaneous (n = 364), mucosal (n = 88), and cutaneous (n = 42). Among them, 235 cases had received cotrimoxazole as a prophylaxis and 259 patients did not. The incidence of PCP in total patients was 2 (0.4%), one in each group. Accordingly, no significant difference was observed in the incidence of PCP between two groups (p = 0.84). Also, no cotrimoxazole‐related side effect was observed in the treated group. It seems that due to the low incidence of PCP in pemphigus patients treated with rituximab, prophylactic cotrimoxazole therapy is not necessary and it only increases the overall therapy cost and might cause cotrimoxazole‐related adverse effects in some patients. However, regarding its probable beneficial effect in patients with long‐term history of immunosuppressive therapy, more studies are required. [ABSTRACT FROM AUTHOR]

OBJECTIVES: At normal doses of trimethoprim-sulfamethoxazole (TMP/SMX), trimethoprim inhibits tubular creatinine secretion, leading to a rapid but reversible increase in serum creatinine (SCr). Although patients with connective tissue diseases are often in the state of immunosuppression and TMP/SMX is an important prophylactic drug, clinicians often have to stop or reduce the dosage due to concerns regarding its effect on renal function. This study aimed to evaluate the effect of a prophylactic dose of TMP/SMX on SCr in Japanese patients with connective tissue diseases, the extent of SCr level elevation and the independent risk factors for creatinine elevation. METHODS: A retrospective cohort study was undertaken. Participants included patients with connective tissue diseases who were treated with a prophylactic dose of TMP/SMX between 2004 and 2018. Using single and multiple regression analyses, the risk factors that affected SCr elevation were evaluated. RESULTS: A total of 262 patients, females, n = 181; age, median (range) = 59 (19-89) years, were included. The median baseline SCr level before treatment was 0.62 (0.16-2.1) mg/dL. The median SCr elevation value was 0.07 (-0.54 to 0.84) mg/dL in 4 weeks after TMP/SMX initiation. Five (2%) participants had ≥0.3 mg/dL SCr elevation. Multiple regression analyses, including age, baseline SCr, diuretic use, nonsteroidal anti-inflammatory drug use and diabetes mellitus, indicated that baseline SCr and advanced age were independent risk factors of SCr elevation. CONCLUSIONS: These results demonstrated that baseline SCr and advanced age were associated with SCr elevation by a prophylactic dose of TMP/SMX. However, a prophylactic dose of TMP/SMX rarely elevated the SCr level significantly. Therefore, other causes can be considered if patients show an SCr elevation ≥0.3 mg/dL. [ABSTRACT FROM AUTHOR]

Adverse drug reactions are an emergency, and the first contact physician must be completely familiar with them, since they can compromise the function and even the life of patients. Stevens Johnson syndrome/toxic epidermal necrolysis is one of the most studied and reported adverse reactions to date, with a large number of drugs being associated with its appearance. An early diagnosis and an adequate management of the same results in the reduction of mortality caused by this pathology. We present the case of a 74-year-old patient who presented this event after taking cotrimoxazole. [ABSTRACT FROM AUTHOR]

Evaluation of pediatric hypereosinophilia (HE) is challenging, especially in the tropical developing countries, as appropriate diagnostic facilities may be lacking, parasitic/helminthic infections are common, and existing data on the etiology of severe eosinophilia are sparse. Second, data on long-term follow-up of these children including the temporal course of eosinophilia are also scarce. Besides, questions regarding the coexistence of multiple etiologies and their association with the severity of HE are largely unexplored. These challenges and questions often lead to diagnostic and therapeutic dilemmas. We highlight these difficulties utilizing a real-life clinical description. We emphasize the need for long-term follow-up of such children as HE may be the combinatorial effect of multiple etiologies, rather than a single cause. We also describe an unusual association of severe eosinophilia in a child with toxoplasmosis that was treated successfully with 8-week combination therapy with azithromycin and cotrimoxazole (sulfadiazine and pyrimethamine were not available). [ABSTRACT FROM AUTHOR]

Background: Little is known regarding the optimal management of nocardiosis among solid organ transplant (SOT) recipients. It is often suggested to avoid trimethoprim/sulfamethoxazole (TMP‐SMX) monotherapy in heavily immunocompromised patients (such as SOT recipients) and/or in case of severe or disseminated nocardiosis. Our aim was to report our experience with TMP‐SMX monotherapy in SOT recipients with nocardiosis. Methods: Using data from a previously published European study, we assessed the incidence of adverse events in SOT recipients receiving TMP‐SMX monotherapy and assessed its effectiveness. Results: Thirty‐one SOT recipients with nocardiosis were included, mostly kidney transplant recipients (20/31, 65%). Eleven (36%) had disseminated infection, and four (13%) had brain nocardiosis. Most patients had lung and/or pleural involvement (26/31, 84%). Daily dose of trimethoprim at initiation was 10 [6.4‐14.8] mg/kg. The median estimated glomerular filtration rate at time of diagnosis of nocardiosis was 44 [30‐62] ml/min/1.73 m². TMP‐SMX was discontinued prematurely in one third of the patients (10/31, 32%, mostly for hematological toxicity [n = 3] or increased serum creatinine [n = 3]). Focusing on the 24 (77%) patients who completed at least 30 days of TMP‐SMX monotherapy, 4 had late (>30 days) drug discontinuation, 1 experienced treatment failure, and 19 completed planned TMP‐SMX monotherapy. Clinical outcome was favorable in these 19 patients, despite the fact that 8 (42%) had disseminated infection and 2 (11%) brain nocardiosis. Overall, all‐cause 1‐year mortality was 10% (3/31). Conclusions: TMP‐SMX monotherapy appears to be effective for the treatment of most nocardiosis among SOT recipients. Interventional studies are needed to compare its safety and effectiveness with those of other regimens used to treat posttransplant nocardiosis. [ABSTRACT FROM AUTHOR]

Background and Aim: Urinary tract infection is one of the most common childhood diseases. The results of studies investigating discontinuation or continuation of antibiotics in children with recurrent urinary tract infections and urinary reflux are controversial. Therefore, this study was conducted to compare prophylactic antibiotic treatment twice a week versus every night in the recurrence of urinary tract infections in children. Methods: This clinical trial was conducted using non-random simple sampling. Group A was given a single daily dose of cephalexin 10 mg/kg and group B was given cotrimoxazole at a dose of 5 mg/kg. Both groups were followed for ten months. Recurrences of urinary tract infections were compared between the two groups. Results: The mean age of the participants was 3.53±2.04 years. Most of the subjects were female (n=37, 61.7%). Urinary reflux was unilateral in 65% of the cases (n=39) and bilateral in the rest. There was no significant difference in age distribution, sex, and type of reflux between groups A and B. The frequency of recurrent urinary tract infection was 8.3% in group A and 6.7% in group B indicating no significant difference (p = 0.500). Conclusion: The results of this study showed that the frequency of recurrence of urinary tract infections in children who received prophylactic antibiotic treatment twice a week was not significantly different compared to the group of children who received continuous antibiotic prophylaxis. [ABSTRACT FROM AUTHOR]

Background: Pediatric tuberculosis (TB), human immunodeficiency virus (HIV), and TB-HIV co-infection are health problems with evidence-based diagnostic and treatment algorithms that can reduce morbidity and mortality. Implementation and operational barriers affect adherence to guidelines in many resource-constrained settings, negatively affecting patient outcomes. This study aimed to assess performance in the pediatric HIV and TB care cascades in Mozambique. Methods: A retrospective analysis of routine PEPFAR site-level HIV and TB data from 2012 to 2016 was performed. Patients 0–14 years of age were included. Descriptive statistics were used to report trends in TB and HIV indicators. Linear regression was done to assess associations of site-level variables with performance in the pediatric TB and HIV care cascades using 2016 data. Results: Routine HIV testing and cotrimoxazole initiation for co-infected children in the TB program were nearly optimal at 99% and 96% in 2016, respectively. Antiretroviral therapy (ART) initiation was lower at 87%, but steadily improved from 2012 to 2016. From the HIV program, TB screening at the last consultation rose steadily over the study period, reaching 82% in 2016. The percentage of newly enrolled children who received either TB treatment or isoniazid preventive treatment (IPT) also steadily improved in all provinces, but in 2016 was only at 42% nationally. Larger volume sites were significantly more likely to complete the pediatric HIV and TB care cascades in 2016 (p value range 0.05 to < 0.001). Conclusions: Mozambique has made significant strides in improving the pediatric care cascades for children with TB and HIV, but there were missed opportunities for TB diagnosis and prevention, with IPT utilization being particularly problematic. Strengthened TB/HIV programming that continues to focus on pediatric ART scale-up while improving delivery of TB preventive therapy, either with IPT or newer rifapentine-based regimens for age-eligible children, is needed. [ABSTRACT FROM AUTHOR]

Introduction. Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE or baboon syndrome) is an uncommon form of systemic contact dermatitis, readily differentiated from other drug eruptions by its peculiar appearance. Case report. A 48-year-old male presented with itchy erythematous rash with blisters two days after taking an unknown drug. Dermatological examination revealed symmetrical erythematous macules with large bullae over the anterior trunk, neck, inner thighs and axillae. Systemic examination and laboratory parameters were normal. A diagnosis of symmetrical drug-related intertriginous and flexural exanthema associated with cotrimoxazole was made based on dermatological findings, histopathology and the reappearance of lesions after administration of cotrimoxazole (trimethoprim 160 mg and sulfamethoxazole 800 mg twice daily). Coincidentally, he was detected to be HIV seropositive and started a highly active antiretroviral therapy. His skin lesions resolved with systemic glucocorticosteroids. Conclusions. Patients and clinicians should be aware of the possibility of a baboon syndrome due to cotrimoxazole, a widely used drug. [ABSTRACT FROM AUTHOR]

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection that mostly affects children with suppressed cellular immunity. PJP was the most common cause of infectious death in children with acute lymphoblastic leukemia prior to the inclusion of cotrimoxazole prophylaxis as part of the standard medical care in the late 1980s. Children with acute leukemia, lymphomas, and those undergoing hematopoietic stem cell transplantation, especially allogeneic transplantation, are also at high risk of PJP. Persistent lymphopenia, graft versus host disease, poor immune reconstitution, and lengthy use of corticosteroids are significant risk factors for PJP. Active infection may be due to reactivation of latent infection or recent acquisition from environmental exposure. Intense hypoxemia and impaired diffusing capacity of the lungs are hallmarks of PJP, while computerized tomography of the lungs is the diagnostic technique of choice. Immunofluorescence testing with monoclonal antibodies followed by fluorescent microscopy and polymerase chain reaction testing of respiratory specimens have emerged as the best diagnostic methods. Measurement of (1-3)-β-D-glucan in the serum has a high negative predictive value in ruling out PJP. Oral cotrimoxazole is effective for prophylaxis, but in intolerant patients, intravenous and aerosolized pentamidine, dapsone, and atovaquone are effective alternatives. Intravenous cotrimoxazole is the treatment of choice, but PJP has a high mortality even with appropriate therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND Cotrimoxazole, which has been one of the drugs of choice for urinary tract infections (UTIs) since 1960, must be evaluated to determine whether it is still a relevant drug for this use. This study aimed to assess the susceptibility patterns to cotrimoxazole of the bacteria that cause UTIs from urine samples of female outpatients (community-acquired [CA]-UTI) and inpatients (hospital-acquired [HA]-UTI) in Jakarta. METHODS This study was conducted from December 2014 to December 2015. Susceptibility testing of bacteria causing UTIs was conducted on 27 of 311 female outpatient urine samples collected from six clinics in Jakarta, and secondary data susceptibility testing was performed on 27 of 107 urine samples of inpatients from hospitals in Jakarta. These samples were examined in the Clinical Microbiology Laboratory, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital. RESULTS Susceptibility to cotrimoxazole was reported in 83% of the bacteria causing UTIs in CA-UTI and 44% of the bacteria in HA-UTI patients. Klebsiella pneumoniae was the most common cause of CA-UTI, with all isolates susceptible to cotrimoxazole (100%). Conversely, Escherichia coli was the most common cause of HA-UTI but was only susceptible in some isolates (44%). Bacteria from CA-UTI patients were almost twice as susceptible to cotrimoxazole compared with HA-UTI patients (p = 0.003). CONCLUSIONS Based on the susceptibility patterns identified, cotrimoxazole can be used as a treatment for CA-UTI but not for HA-UTI patients in Jakarta, Indonesia. [ABSTRACT FROM AUTHOR]

Typhoid fever is a disease caused by Salmonella Typhi and commonly treated by an antimicrobial agent such as cotrimoxazole. Natural product and some plant extract usage have risen as an adjunctive therapy to treat many diseases. Aim of the study * To increase anti-salmonella efficacy of cotrimoxazole by combing with aqueous seed extract of Punicgranatum. * To prevent salmonella Typhi resistant by combination of antibiotic which is proved to treat this microorganism with aqueous extract of Punicagranatum? Material and method S.Typhi had been isolated and spp. Identified to be prepared as a module of anti-salmonella, isolation microorganisms cultivated for MIC determination of cotrimoxazole and aqueous Punic extract each one alone and their combination index. Result The minimum inhibitory concentration assay of the test combination between cotrimoxazole and the aqueous extract of Punicgranatum in micro/ml showed a noticeable increase in potency by combining the two test agents from 125 microgram /ml, 250 microgram/ml to 62.5 microgram/ml in cotrimoxazole, aqueous extract of Punicgranatum and the combination respectively P-value <0.05. Conclusion There was a strong synergism between cotrimoxazole and p. granatum aqueous extract against Salmonella Typhi in culture. [ABSTRACT FROM AUTHOR]

Background: Multiple drug resistance has become a major threat to the treatment of cholera. Recent studies in Kenya have described the epidemiology, especially the risk factors, of cholera; however, there is little information on the phenotypic and drug susceptibility patterns of Vibrio cholerae (V. cholerae) in outbreaks that in the recent past have occurred in western Kenya. Aim: To characterise and determine the antibiotics' susceptibility profiling of toxigenic V. cholerae isolates from Kisumu County. Setting: The project was conducted in Kisumu County, Kenya. Methods: A total of 119 V. cholerae O1, biotype El Tor, isolates collected during 2017 cholera outbreak in Kisumu County were used for this study. The samples were cultured on thiosulphate-citrate-bile salts sucrose (TCBS) agar and biochemical tests were carried out using standard procedures. Susceptibility tests were conducted by using various conventional antibiotics against standard procedures. Results: Of the 119 isolates, 101 were confirmed to be V. cholerae belonging to serotypes Inaba and Ogawa, with Inaba being the predominant serotype (73.95%). The isolates were susceptible to ciprofloxacin (100%), ofloxacin (100%), gentamycin (100%), doxycycline (99%), ceftriaxone (99%) and streptomycin (96.04%) antimicrobials, and resistant to erythromycin (53.47%), amoxicillin (64.4%), nalidixic acid (83.2%) and ampicillin (89.11%), with high resistance to cotrimoxazole (99%) and tetracycline (97%). Conclusion: Vibrio cholerae was resistant to multiple antibiotics, including those commonly used in the management of cholera. Taken together, there is a need to carry out regular surveillance on antimicrobial drug resistance during outbreaks. [ABSTRACT FROM AUTHOR]

Stenotrophomona maltophilia is a Gram negative bacterium, long considered a saprophytic microorganism with limited pathogenicity. Recent reports associate it with an increase in morbidity and mortality, because it has the characteristic of being multiresistant to the antimicrobials used. The bacterium causing septicemic infection was identified in a nursing patient and its specific treatment was established to obtain optimal results in its management. S. maltophilia is an opportunistic bacterium that was identified in an immunocompromised patient who received multiple antimicrobial treatment, the pathogen took a behavior that induced complications and, despite being multiresistant, was highly sensitive to treatment with cotrimoxazole. In the present article we report the case of a 17-month-old male patient belonging to the Huichol ethnic group, malnourished, who went to the hospital for presenting a diarrheic syndrome with electrolyte imbalance, acute renal failure and hypovolemic shock and infectious toxicity. The patient was hospitalized for 30 days, with a torpid evolution and a poor response to the initial empirical antimicrobial treatment based on meropenem, vancomycin, linezolid and caspofungin for 14 days. During the hospital stay, the bacterium S. maltophilia, which was resistant to several antimicrobials but sensitive to trimethoprim with sulfamethoxazole (cotrimoxazole), was isolated from the blood culture, so that antimicrobial scheme was initiated for 10 days obtained a satisfactory response with clinical, laboratorial, metabolic and hemodynamic improvement. The control blood culture three weeks after admission was reported negative and the patient was discharged in good general conditions and without apparent sequelae. [ABSTRACT FROM AUTHOR]

Background: Cotrimoxazole is associated with the development of hyponatremia, hyperkalemia and elevated serum creatinine, especially when combined with inhibitors of the renin–angiotensin–aldosterone system (RAAS). Pneumocystis jirovecii pneumonia (PJP) prophylaxis is the standard of care for high-grade glioma (HGG) patients receiving temozolomide concurrently with radiotherapy, low-dose cotrimoxazole being the preferred agent. Many of these patients are also taking renin–angiotensin–aldosterone system inhibitors, however the risk of significant laboratory disturbance in these patients remains undescribed. Objective: We evaluated whether high-grade glioma patients taking renin–angiotensin–aldosterone system inhibitors receiving low-dose cotrimoxazole for Pneumocystis jirovecii pneumonia prophylaxis are at additional risk of laboratory disturbances in comparison with their non-renin–angiotensin–aldosterone system counterparts. Methods: We conducted a retrospective chart review of adult neuro-oncology patients treated for WHO Grade III or IV glioma between 2013 and 2016. Patient serum Na, K, creatinine, and eGFR were compared (renin–angiotensin–aldosterone system vs. non-renin–angiotensin–aldosterone system) using the chi-square test. Binary logistic regression analysis was then performed to account for differences between cohorts. Results: Of 63 patients (35 non-renin–angiotensin–aldosterone system, 28 renin–angiotensin–aldosterone system), patients in the renin–angiotensin–aldosterone system cohort were more likely to experience a laboratory disturbance (odds ratio=3.17, p = 0.03). Overall, these disturbances were moderate, but were slightly more common and slightly more severe in the renin–angiotensin–aldosterone system cohort. Conclusion: Adding low-dose cotrimoxazole for Pneumocystis jirovecii pneumonia prophylaxis to the regimens of patients with high-grade glioma taking renin–angiotensin–aldosterone system inhibitors increases the risk of laboratory disturbances. While these are generally moderate, some patients are at risk of significant electrolyte abnormalities requiring intervention. [ABSTRACT FROM AUTHOR]

• Between 2010 and 2017, 30 patients with bone and joint infections caused by Enterobacter cloacae were treated with a fluoroquinolone–cotrimoxazole combination for 8–12 weeks. • The cure rate of the fluoroquinolone–cotrimoxazole combination was 80% by intention-to-treat analysis and 89% per protocol with a mean follow-up of 29.3 (standard deviation 19.1) months. • No relapse of E. cloacae infection was observed. Although the frequency of bone and joint infections caused by Enterobacter spp. is increasing, studies regarding the optimal antibiotic therapy are scarce. The objective of this retrospective study was to assess the clinical outcomes and safety of a fluoroquinolone–cotrimoxazole combination for the treatment of bone and joint infections caused by Enterobacter cloacae. Between 2010 and 2017, 30 patients with bone and joint infections caused by E. cloacae were treated with a fluoroquinolone–cotrimoxazole combination for 8–12 weeks. There were 26 cases (87%) of infection of an internal fixation device, two cases (6.6%) of pseudarthrosis with chronic osteomyelitis, and two cases (6.6%) of infection of knee and ankle prosthetic devices. The cure rate of the fluoroquinolone–cotrimoxazole combination was 80% by intention-to-treat analysis, with a mean follow-up of 29.3 ± 19.1 months. The fluoroquinolone–cotrimoxazole combination for 8–12 weeks is effective for the treatment of bone and joint infections caused by E. cloacae. [ABSTRACT FROM AUTHOR]

The article discusses rates of mother-to-child transmission of human immunodeficiency virus (HIV) have falling globally, with 200 000 child infections averted in 2018 due to the implementation of prevention of mother-to-child-transmission interventions. Topics include antimicrobial prophylaxis guidelines for HIV-exposed have developed prior to the availability of antiretroviral therapy; and the World Health Organization recommends HIV-exposed infants receive prophylactic cotrimoxazole.

Pulmonary nocardiosis can occur in both immunocompromised and immunocompetent patients. The case is presented here of pulmonary nocardiosis in an immunocompetent woman that was initially treated with cotrimoxazole. Because of deterioration of renal function and development of hyperkaliemia, the patient's treatment was changed to levofloxacin, which was continued for 11 months. The treatment resulted in improvement of her clinical status and complete normalization of the laboratory tests. The clinical importance of this case lies in the fact that in the relevant bibliography, only a few cases of pulmonary nocardiosis were treated successfully with levofloxacin. [ABSTRACT FROM AUTHOR]

Transplantation activity is increasing, leading to a growing number of patients at risk for toxoplasmosis. We reviewed toxoplasmosis prevention practices, prevalence, and outcomes for hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT; heart, kidney, or liver) patients in Europe. We collected electronic data on the transplant population and prevention guidelines/regulations and clinical data on toxoplasmosis cases diagnosed during 2010-2014. Serologic pretransplant screening of allo-hematopoietic stem cell donors was performed in 80% of countries, screening of organ donors in 100%. SOT recipients were systematically screened in 6 countries. Targeted anti-Toxoplasma chemoprophylaxis was heterogeneous. A total of 87 toxoplasmosis cases were recorded (58 allo-HSCTs, 29 SOTs). The 6-month survival rate was lower among Toxoplasma-seropositive recipients and among allo-hematopoietic stem cell and liver recipients. Chemoprophylaxis improved outcomes for SOT recipients. Toxoplasmosis remains associated with high mortality rates among transplant recipients. Guidelines are urgently needed to standardize prophylactic regimens and optimize patient management. [ABSTRACT FROM AUTHOR]

Combinations of linezolid (LZD) or trimethoprim/sulfamethoxazole (SXT) plus rifampicin (RIF) are alternative oral treatments for staphylococcal prosthetic joint infections (PJIs) when fluoroquinolones are not possible to use, but there is limited evidence regarding their activity. This study evaluated the efficacy of LZD and SXT, alone and in combination with RIF, against Staphylococcus aureus in an in vitro pharmacokinetic/pharmacodynamic biofilm model. Using the CDC Biofilm Reactor ® system, simulated regimens of LZD (600 mg every 12 h), SXT (160/800 mg every 8 h) and levofloxacin (LVX) (750 mg/day), alone and in combination with RIF (600 mg/day), were evaluated against one methicillin-susceptible S. aureus (MSSA) and one methicillin-resistant S. aureus (MRSA) strain. Antibiotic efficacy was evaluated by the decrease in planktonic bacterial counts from medium and biofilm-embedded bacteria from coupons over 56 h. Resistant strains were screened. In both strains, SXT alone was ineffective and LZD presented low activity, but no resistance emerged. Combinations with RIF significantly increased the antibiofilm efficacy against MSSA (Δlog CFU/mL 56h–0h: SXT + RIF, −2.9 and LZD + RIF, −3.1), but RIF-resistant strains appeared with SXT + RIF. Against MRSA, LZD + RIF (−3.1) protected against the emergence of resistance and was more effective than SXT + RIF (−0.6; P  <   0.05), in which RIF-resistant strains were again detected. LVX + RIF confirmed its high efficacy against biofilm-embedded bacteria, this being the most effective therapy (−5.1 against MSSA). The emergence of RIF-resistant strains with SXT + RIF poses serious concerns for its use in clinical practice. Interestingly, LZD + RIF appears to be an appropriate alternative for PJI caused by LVX-resistant S. aureus . [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported the antifertility activities of sulfonamides. This study was designed to evaluate the effects of co-trimoxazole and its co-administration with folic acid on ovarian tissue in female rats. Methods: A total of 54 rats were randomly divided into 9 groups (n=6). Group I served as the control and group II (vehicle) received saline. Other groups, III to IX, received co-trimoxazole (30, 60, and 120 mg/kg; i.p.), folic acid (1 mg/kg; i.p.) or their combination for 14 days, respectively. The oocytes were obtained from each group at the end of the 14th days and scored for maturational status as germinal vesicle (GV), metaphase I (MI), or metaphase II (MII). The number of primordial follicle (PrF), primary follicle (PF), and secondary follicle in formalin-fixed ovaries were counted under light microscopy. The data were analyzed by one-way ANOVA followed by post-hoc Dunnet test using SPSS statistical software (version 17.0). Results were considered statistically significant at P<0.05. Results: Co-trimoxazole (60 and 120 mg/kg) treatment for 14 days caused a significant decrease in the number of GV (P=0.02, P<0.001), MI and MII (P=0.03, P<0.001), a significant increase in structural abnormalities, including PrF, PF and secondary follicle (P<0.001) as well as congestion, inflammation and necrosis of ovarian tissue compared to the vehicle group. Folic acid co-administration with co-trimoxazole reversed partially all these parameters compared to the co-trimoxazole group (P<0.001). Conclusion: The data showed the adverse effects of co-trimoxazole on the ovarian maturational status and tissue structure which was reversed partially by folic acid co-administration in rats. [ABSTRACT FROM AUTHOR]

Introduction: Cotrimoxazole (CTX) should be given to all HIV-infected adults with mild or severe HIV-disease or those with CD4 counts below 350/mm3 according to 2006 WHO guidelines. We assessed the impact of CTX prophylaxis on the risk of malaria episodes in HIV-1-infected adults from four West African countries with different patterns of malaria transmission.Method: Multicentric cohort study, conducted between September 2007 and March 2010 in four West African cities. Antiretroviral therapy (ART) naïve HIV-infected adults started CTX at enrolment (CTX group) if they had CD4 < 350 cells/mm3 or were at WHO clinical stage ≥2. For patients who did not start CTX at enrolment (non-CTX group) and started CTX afterwards, follow-up was censored at CTX initiation. We used Cox's proportional hazard model to compare the risk of malaria between CTX groups.Results: A total of 514 participants (median CD4 count 238 cells/mm3 ) were followed for a median of 15 months. At enrolment, 347 started CTX, and 261 started ART. During the follow-up, 28 started CTX. The incidence of malaria was 8.7/100 PY (95%CI 6.3-11.5) overall, 5.2/100 PY (95%CI 3.1-8.3) in the CTX group and 15.5/100 PY (95%CI 10.3-22.1) in the non-CTX group. In multivariate analysis, CTX led to a 69% reduction in the risk of malaria (aHR 0.31, 95%CI 0.10-0.90).Conclusion: Patients in the CTX group had an adjusted risk of malaria three times lower than those in the non-CTX group. The prolonged large-scale use of CTX did not blunt the efficacy of CTX to prevent malaria in this region. [ABSTRACT FROM AUTHOR]

Background and Aim: In the last few decades co-trimoxazole, an antibacterial combination of trimethoprim and sulfamethoxazole, has been used for treatment of bacterial infections, but due to the vast usage of these drugs, resistant strains have appeared throughout the world. One of the reasons for resistance to co-trimoxazole is related to drf genes, which are responsible for trimethoprim resistance, while the sulfamethoxazole resistance is due to sulfonamide sul genes. The aim of this study was to investigate drug resistance and frequencies of resistance genes in gram-negative bacteria isolated from clinical specimens. Materials and Methods: Clinical samples were collected from patients in Pars Hospital, Tehran, Iran, in which presence of gram-negative bacteria was confirmed by biochemical tests. Then antibiotic susceptibility tests were performed for 5 antibiotics by disk diffusion agar technic. DNA was extracted from bacteria resistant to co-trimoxazole, followed by PCR using specific primers for sul1, sul2, sul3, and drf7 genes. Results: In the co-trimoxazole-resistant bacteria, 26%, 74%, 2% and 16% of the isolates contained sul1 gene, sul2 gene, sul3 gene and drf7 gene, respectively. Further analysis of the data showed that 51% of the isolates were resistant to gentamicin, 74% to ceftriaxone, 65% to ciprofloxacin and 3% to colistin. For resistance to trimethoprim only the drf 7 gene was used. Conclusion: The results of this study show that in the isolates of co-trimoxazole-resistant gram-negative bacteria, the sul 2 gene has a major role in development of resistance to sulfonamides. In this study only the drf 7 gene was used to assess the resistance of trimethoprim, so we recommend to conduct studies also on other drf genes, so that the importance of each in resistance to co-trimoxazole can be determined. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is one of the greatest threats to human health worldwide. The rate of development of newer antibiotics is much slower than the rate of development of antibiotic resistance. A survey reported that it takes 15 years and US$800 million (including preclinical and clinical costs) to bring a single drug to the market, whereas the reuse of the older drugs for antimicrobial use takes $17 million, thereby circumventing 40% of the overall cost. The first case is a patient with nosocomial pyrexia of unknown origin who was given treatment with tigecycline and cefepime/tazobactam but failed to respond to the same. However, the patient responded to the treatment with cotrimoxazole. The second case is a patient with meningitis caused by an atypical zoonotic pathogen, Staphylococcus chromogenes. This is the first report of human infection with S. chromogenes, this being a common cause of bovine mastitis. The isolate was obtained from a patient of neurotrauma who developed meningitis after decompressive craniotomy. The strain was obtained from cerebrospinal fluid, blood, and shunt chamber pus. Cotrimoxazole was given for the treatment, and the patient improved after the treatment. Although the newer antibiotics have replaced sulfonamides in the treatment of many infections, they are still of great value and are the agents of choice in many infections. Sulfonamides have wide antimicrobial activity against both Gram‑positive and Gram‑negative bacteria, but their usefulness has diminished with the emergence of resistant strains. This paper reports cases of two different kinds of infections from a level 1 trauma center, who failed to respond to the newer antibiotics but showed a response to administration of cotrimoxazole. [ABSTRACT FROM AUTHOR]

Background:  Cotrimoxazole (CTX) discontinuation increases malaria incidence in human immunodeficiency virus (HIV)-infected individuals. Rates, quantity, and timing of parasitemia rebound following CTX remain undefined.Methods:  Serial specimens from a trial of HIV-infected individuals receiving antiretroviral treatment (ART) randomized to continue (the CTX arm) or discontinue (the STOP-CTX arm) were examined for malaria parasites by quantitative reverse transcription polymerase chain reaction (PCR). Specimens obtained at enrollment and then quarterly for 12 months and at sick visits were assessed; multiplicity of infection was evaluated by PCR that targeted the polymorphic msp-1/msp-2 alleles.Results:  Among 500 HIV-infected adults receiving ART (median ART duration, 4.5 years), 5% had detectable parasitemia at baseline. After randomization, parasite prevalence increased over time in the STOP-CTX arm, compared with the CTX arm, with values of 4% and <1%, respectively, at month 3, 8% and 2% at month 6, 14% and 2% at month 9, and 22% and 4% at month 12 (P = .0034). The combined mean parasite density at the various time points was higher in the STOP-CTX arm (4.42 vs 3.13 log10 parasites/mL; P < .001). The parasitemia incidence was 42.0 cases per 100 person-years in the STOP-CTX arm and 9.9 cases per 100 person-years in the CTX arm, with an incidence rate ratio of 4.3 (95% confidence interval, 2.7-7.1; P < .001). After enrollment, mixed infections (multiplicity of infection, >1) were only present in the STOP-CTX arm.Conclusion:  Discontinuation of CTX by HIV-infected adults receiving ART resulted in progressive increases in malaria parasitemia prevalence and burden.Clinical Trials Registration:  NCT01425073. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial prophylaxis is recommended for the prevention of urinary tract infections (UTI) in high-risk children. However, there is growing concern about the use of β-lactams as prophylaxis and subsequent development of antibiotic resistance. Methods: In this prospective, randomized, crossover controlled trial we compared cotrimoxazole (SXT) and second-generation cephalosporins (2GC) as UTI prophylaxis in children ranging in age from 1 to 60 months. Eligible patients were 1:1 randomized to receive either SXT or 2GC for the initial 6-month period (1 course), then switched to the other antimicrobial agent class for the subsequent course, with switching continuing after each course until the end of the study. Urethral orifice cultures (UOCs) were obtained at the time of switching antimicrobial prophylaxis. Results: Among 97 children (mean age 13.6 months) on prophylaxis, breakthrough UTIs occurred during 13.3 % (10/75) of SXT courses and 10.3 % (8/78) of 2GC courses ( p = 0.62). 2GC failed earlier than SXT (mean ± standard error: 0.81 ± 0.1 vs. 2.37 ± 0.36 months, respectively; p = 0.028). Pseudomonas aeruginosa and Enterococcus spp. were more frequently isolated after 2GC courses than after SXT courses [22.6 vs. 4.8 % ( p = 0.02) and 20.7 vs. 4.8 % ( p = 0.035), respectively]. Prophylaxis with 2GC significantly increased resistance to both 2GC and SXT, while SXT prophylaxis did not affect susceptibility to 2GC. Conclusions: While SXT and 2GC appear to be equally efficacious as UTI prophylaxis in children, the latter exert a broader effect on patients' flora and development of bacterial resistance, suggesting that SXT may be more appropriate for UTI prophylaxis than 2GC. [ABSTRACT FROM AUTHOR]

Background. The growth benefits of cotrimoxazole during early antiretroviral therapy (ART) are not well characterized. Methods. Individuals enrolled in the Therapeutics Research, Education, and AIDS Training in Asia Pediatric HIV Observational Database were included if they started ART at ages 1 month-14 years and had both height and weight measurements available at ART initiation (baseline). Generalized estimating equations were used to identify factors associated with change in height-for-age z-score (HAZ), follow-up HAZ≥-2, change in weight-for-age z-score (WAZ), and follow-up WAZ≥-2. Results. A total of 3217 children were eligible for analysis. The adjusted mean change in HAZ among cotrimoxazole and non-cotrimoxazole users did not differ significantly over the first 24 months of ART. In children who were stunted (HAZ < -2) at baseline, cotrimoxazole use was not associated with a follow-up HAZ≥-2. The adjusted mean change in WAZ among children with a baseline CD4 percentage (CD4%) >25% became significantly different between cotrimoxazole and non-cotrimoxazole users after 6 months of ART and remained significant after 24 months (overall P < .01). Similar changes in WAZ were observed in those with a baseline CD4% between 10% and 24% (overall P < .01). Cotrimoxazole use was not associated with a significant difference in follow-up WAZ in children with a baseline CD4% <10%. In those underweight (WAZ < -2) at baseline, cotrimoxazole use was associated with a follow-upWAZ≥-2 (adjusted odds ratio, 1.70 vs not using cotrimoxazole [95% confidence interval, 1.28-2.25], P < .01). This association was driven by children with a baseline CD4% ≥10%. Conclusions. Cotrimoxazole use is associated with benefits to WAZ but not HAZ during early ART in Asian children. [ABSTRACT FROM AUTHOR]

Background: Coinfection with malaria and HIV is common in Sub-Saharan Africa. In the advent of a decline in the global incidence of malaria, it is important to generate updated data on the burden of malaria in people living with HIV (PLWHIV). This study was designed to determine the prevalence of malaria in PLWHIV in Yaounde, Cameroon, as well determine the association between CD4 (+) T cell count and malaria in the study population.Methods: In a cross sectional study performed between April 2015 and June 2016, 355 PLWHIV were enrolled and blood samples were collected for analysis. Complete blood count was performed using an automated haematology analyser (Mindray®, BC-2800) and CD4 (+) T cell count was performed using a flow cytometer (BD FASCount™). Giemsa-stained blood films were examined to detect malaria parasite. The Pearson's chi-square, student's T-test, ANOVA, and correlation analysis were all performed as part of the statistical analyses.Results: The prevalence of malaria observed in the study was 7.3 % (95 % CI: 4.8-10.6). No significant association was observed between the prevalence of malaria and age or gender. The prevalence of malaria was higher in participants who were not sleeping in insecticide treated bed nets, ITNs (p < 0.001); and in participants who were not on cotrimoxazole prophylaxis (p = 0.002). The prevalence of malaria (p < 0.001) and malaria parasite density (p = 0.005) were observed to be progressively higher in participants with CD4 (+) T cell count below 200cells/μl. Furthermore, the mean CD4 (+) T cell count was observed to be lower in participants coinfected with malaria compared to non-coinfected participants (323.5 vs 517.7) (p < 0.001). In this study, a negative correlation was observed between malaria parasite density and CD4 (+) T cell count (p = 0.019).Conclusions: A low prevalence of malaria was observed in the study population. Some of the factors accounting for the low prevalence of malaria in this study population may include the health seeking habit of PLWHIV, the use of cotrimoxazole based chemoprophylaxis, and their cautious use of ITNs. [ABSTRACT FROM AUTHOR]

Background: The effect of CD4 count on malaria incidence in HIV infected adults on antiretroviral therapy (ART) was assessed in the context of a randomized controlled trial on the effect of stopping cotrimoxazole (CTX). Methods: This study presents a sub-analysis of the COSTOP trial (ISRCTN44723643) which was carried out among HIV-infected Ugandan adults stable on ART with CD4 counts ≥250 cells/µl. Participants were randomized (1:1) to continue CTX or stop CTX and receive matching placebo, and were followed up for a minimum of 1 year (median 2.5 years). CD4 counts were measured at baseline, 3 months and then every 6 months. Clinical malaria was defined as fever and a positive blood slide. First, the relationship between current CD4 count during follow-up and malaria among participants on placebo was examined; using random effects Poisson regression to account for repeated episodes. Second, the effect of CD4 count at enrolment, CD4 count at ART initiation, and CD4 count during follow-up on malaria, was assessed within each trial arm; to examine whether the effect of CD4 count differed by CTX use. Results: 2180 participants were enrolled into the COSTOP trial. The incidence of clinical malaria was approximately four episodes/100 person years in the CTX arm and 14 episodes/100 person years in the placebo arm. There was no evidence of an association of current CD4 and clinical malaria incidence (P = 0.56), or parasitaemia levels (P = 0.24), in the placebo arm. Malaria incidence did not differ by CD4 count at ART initiation, enrolment or during follow up, irrespective of CTX use. When compared with participants in the lowest CD4 stratum, rate ratios within each trial arm were all close to 1, and P values were all above P = 0.30. Conclusions: The immune status of HIV infected participants who are stable on ART as measured by CD4 count was not associated with malaria incidence and did not modify the effect of stopping CTX on malaria. The decision of whether to stop or continue CTX prophylaxis for malaria in HIV infected individuals who are stable on ART should not be based on CD4 counts alone. COSTOP trial registration number ISRCTN44723643 [ABSTRACT FROM AUTHOR]

Objectives and design: The general objective of the study was to determine factors associated with cotrimoxazole prophylaxis compliance among HIV exposed infants so that strategies are designed to improve cotrimoxazole prophylaxis uptake and compliance. A cross sectional study was conducted at Chikankata Mission hospital catchment area in Chikankata district. Measures: The study comprised face to face interviews of 102 mothers/caretakers of HIV exposed infants aged 6 weeks to 18 months selected using convenient sampling method. These mothers/caretakers of HIV exposed infants were interviewed using a structured interview schedule. The study data collection was done from September to November 2014 over a period of 2-3 months whereby 3-5 questionnaires were administered per day due to limited sampling frame. SPSS statistical package was used for data entering and analysis. Descriptive statistics were employed to illustrate the data and chi-square test was used test associations among variables. The p values of less than 0.05 were considered statistically significant. Results: The findings showed that 78.7% of the respondents were non compliant with cotrimoxazole prophylaxis, 95% had heard about cotrimoxazole prophylaxis and their source of information was the health worker (98%). Though knowledge on the uses of cotrimoxazole prophylaxis stood at sixty percent (60%) only 51% knew the benefits of cotrimoxazole prophylaxis. 75.5% of the respondents stated that cotrimoxazole was not available at the health facilities, 89.2% stated that the road between their respective homes and the nearest health facility was passable, 73% said that the health workers at their nearest health facility did not encourage them to collect the drug when it ran out and 53.9% said that nurses at the nearest health facility did not follow them up when they did not go back for resupply of the drug. 77.5% of the respondents stated that their spouses did not allow them to collect cotrimoxazole when it ran out, 89.2% reported that their spouses knew about their HIV status and 65.7% said that they felt free to give their child cotrimoxazole in public.61.8% of the respondents did not know that there was a social support group for mothers/caretakers of HIV exposed infants in their community and 74.5% stated that there were misconceptions about cotrimoxazole in the communities where they live. Conclusions: The study showed a significant association between compliance to cotrimoxazole prophylaxis and the following factors: non availability of drugs (P=<0.0001), attitude of the health care providers at nearest health facility (P=<0.001), lack of follow up (P=0.009), and impassable roads (P=0.026) as service related factor. There was also a significant association between compliance to the drug and the following sociocultural factors; misconceptions (P=<0.001), spouse not allowing mother/caretakers to collect the drug when it ran out (P=0.001), lack of social support (P=0.002), lack of knowledge of the benefit of cotrimoxazole (P=0.002) and mother/caretaker feeling free to give cotrimoxazole to the child in public (P=0.009). [ABSTRACT FROM AUTHOR]

Background: Cotrimoxazole (CTX) prophylaxis, recommended in HIV-exposed uninfected (HEU) children primarily against HIV-related opportunistic infections, has been shown to have some efficacy against Plasmodium falciparum malaria. The effects of CTX prophylaxis on the acquisition of P. falciparum antigen specific CD4+ T cells-mediated immunity in HEU children is still not fully understood. Methods: Peripheral blood was collected from HEU and HIV-unexposed uninfected (HUU) children at 6, 12 and 18 months of age. Proportion of CD4+ T cells subsets were determined by immunophenotyping. P. falciparum antigen-specific CD4+ T cells responses were measured by intracellular cytokine staining assay. Results: There were no differences in the proportions of naïve, effector and memory CD4+ T cell subsets between HEU and HUU children at all ages. There was a trend showing acquisition of P. falciparum-specific IFN-γ and TNFproducing CD4+ T cells with age in both HUU and HEU children. There was, however, lower frequency of P. falciparumspecific IFN-γ-producing CD4+ T cells in HEU compared to HUU at 6 and 12 months, which normalized 6 months after stopping CTX prophylaxis. Conclusion: The results demonstrate that there is delayed acquisition of P. falciparum-specific IFN-γ-producing CD4+ T cells in HEU children on daily cotrimoxazole prophylaxis, which is evident at 6 and 12 months of age in comparison to HUU age-matched controls. However, whether this delayed acquisition of P. falciparum-specific IFN-γ-producing CD4+ T cells leads to higher risk to malaria disease remains unknown and warrants further investigation. [ABSTRACT FROM AUTHOR]

Rheumatic heart disease (RHD) remains highly prevalent in resource-constrained settings around the world, including countries with high rates of HIV/AIDS. Although both are immunemediated diseases, it is unknown whether HIV modifies the risk or progression of RHD. We performed screening echocardiography to determine the prevalence of latent RHD in 488 HIV-infected children aged 5-18 in Kampala, Uganda. The overall prevalence of borderline/definite RHD was 0.82% (95% confidence interval: 0.26% to 2.23%), which is lower than the published prevalence rates of 1.5%-4% among Ugandan children. There may be protective factors that decrease the risk of RHD in HIV-infected children. [ABSTRACT FROM AUTHOR]