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Objective: This study aimed to assess the overall antibiotic susceptibility of Cutibacterium acnes (C. acnes), a bacterium implicated in acne vulgaris, with a particular focus on clindamycin and fluoroquinolones, which are commonly used in inflammatory acne treatment. Methods: A systematic search of Scopus, PubMed, Web of Science and EMBASE databases was conducted to identify relevant studies. Pooled prevalence estimates were calculated using a random-effects model, and additional analyses included quality assessment, evaluation of publication bias, meta-regression and subgroup analyses based on antimicrobial susceptibility methods and year of publication. Results: The analysis incorporated a total of 39 studies. The random-effects model revealed that the proportion of clindamycin-resistant isolates was 0.031 (95% CI: 0.014–0.071). Additionally, macrolides, including erythromycin (0.366; 95% CI: 0.302–0.434) and azithromycin (0.149; 95% CI: 0.061–0.322), exhibited distinct prevalence rates. Tetracyclines, including doxycycline (0.079; 95% CI: 0.014–0.071), tetracycline (0.062; 95% CI: 0.036–0.107) and minocycline (0.025; 95% CI: 0.012–0.051), displayed varying prevalence estimates. Fluoroquinolones, including ciprofloxacin (0.050; 95% CI: 0.017–0.140) and levofloxacin (0.061; 95% CI: 0.015–0.217), demonstrated unique prevalence rates. Additionally, the prevalence of the combination antibiotic trimethoprim/sulfamethoxazole (SXT) was estimated to be 0.087 (95% CI: 0.033–0.208). Conclusion: The study findings highlight a concerning increase in antimicrobial-resistant C. acnes with the use of antibiotics in acne treatment. The strategic utilization of appropriate antimicrobials has emerged as a crucial measure to mitigate the emergence of antimicrobial-resistant skin bacteria in acne management.

Abstract 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.

Background: Rapid diagnostic test (mRDT) is a useful tool in demonstrating parasitologically proven malaria. Its efficacy is however hampered when parasite density is low. Prophylactic use of cotrimoxazoleas in cases of HIV infected children can cause reduction in parasite count. It is doubtful if mRDT will retain its diagnostic usefulness among such individuals. Objectives: The study sought to evaluate the diagnostic value of mRDT in HIV infected children on cotrimoxazole prophylaxis in Benin City. Methods: In the prospective, cross-sectional and descriptive study, we assessed malaria parasitaemia using standard methods in microscopy and parasite density and malaria antigenaemia using Care Start Pf (monoclonal antibodies specific to histidine rich protein 2 antigen) in 221 each of HIV infected subjects on cotrimoxazole managed in a specialist clinic and HIV negative controls all seen at the University of Benin Teaching Hospital between April and June 2016. Results: Malaria antigenaemia rate MAr (20.8%) was lower than malaria parasitaemia rate MPr (24.4%) in subjects. MAr (20.8) and MPr (24.4%) in subjects were higher than Mar (18.10%) and MPr (17.7%) in controls. Mean (SEM) parasite count in subjects of was low (50.88 + 2.24 per μ l).Using microscopy as gold standard the sensitivity, specificity, PPV and NPV of mRDT in subjects were 77.8%, 97.6%, 91.3% and 93.1%. Corresponding values in controls were 100.0%, 99.5%, 97.5% and 100.0%.Youden indices for subjects and controls were 0.75 and 0.99. Conclusions/Recommendations: Sensitivity of mRDT in HIV infected children on cotrimoxazole prophylaxis for opportunistic infections (OI) is reduced. However the indices of specificity, PPV and NPV are high enough to retain its value in the evaluation of HIV infected children for asymptomatic malaria and perhaps the clinical disease.

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]

Cotrimoxazole, the combined formulation of sulfamethoxazole and trimethoprim, is one of the treatments of choice for several infectious diseases, particularly urinary tract infections. Both components of cotrimoxazole are synthetic antimicrobial drugs, and their combination was introduced into medical therapeutics about half a century ago. In Gram-negative bacteria, resistance to cotrimoxazole is widespread, being based on the acquisition of genes from the auxiliary genome that confer resistance to each of its antibacterial components. Starting from previous knowledge on the genotype of resistance to sulfamethoxazole in a collection of cotrimoxazole resistant uropathogenic Escherichia coli strains, this work focused on the identification of the genetic bases of the trimethoprim resistance of these same strains. Molecular techniques employed included PCR and Sanger sequencing of specific amplicons, conjugation experiments and NGS sequencing of the transferred plasmids. Mobile genetic elements conferring the trimethoprim resistance phenotype were identified and included integrons, transposons and single gene cassettes. Therefore, strains exhibited several ways to jointly resist both antibiotics, implying different levels of genetic linkage between genes conferring resistance to sulfamethoxazole (sul) and trimethoprim (dfrA). Two structures were particularly interesting because they represented a highly cohesive arrangements ensuring cotrimoxazole resistance. They both carried a single gene cassette, dfrA14 or dfrA1, integrated in two different points of a conserved cluster sul2-strA-strB, carried on transferable plasmids. The results suggest that the pressure exerted by cotrimoxazole on bacteria of our environment is still promoting the evolution toward increasingly compact gene arrangements, carried by mobile genetic elements that move them in the genome and also transfer them horizontally among bacteria. [ABSTRACT FROM AUTHOR]

Stenotrophomonas maltophilia is an opportunistic, multidrug-resistant non-fermentative Gram-negative bacillus, posing a significant challenge in clinical treatment due to its numerous intrinsic and acquired resistance mechanisms. This study aimed to evaluate the adequacy of antibiotics used for the treatment of S. maltophilia infections in critically ill patients using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The antibiotics studied included cotrimoxazole, levofloxacin, minocycline, tigecycline, cefiderocol, and the new combination aztreonam/avibactam, which is not yet approved. By Monte Carlo simulations, the probability of target attainment (PTA), the PK/PD breakpoints, and the cumulative fraction of response (CFR) were estimated. PK parameters and MIC distributions were sourced from the literature, the European Committee on Antimicrobial Susceptibility Testing (EUCAST), and the SENTRY Antimicrobial Surveillance Program collection. Cefiderocol 2 g q8h, minocycline 200 mg q12h, tigecycline 100 mg q12h, and aztreonam/avibactam 1500/500 mg q6h were the best options to treat empirically infections due to S. maltophilia. Cotrimoxazole provided a higher probability of treatment success for the U.S. isolates than for European isolates. For all antibiotics, discrepancies between the PK/PD breakpoints and the clinical breakpoints defined by EUCAST (or the ECOFF) and CLSI were detected. [ABSTRACT FROM AUTHOR]

Background: Cotrimoxazole for severe COVID-19 may have a better prognosis because of its antibacterial, immunomodulatory, and anti-inflammatory activities. We examined the efficacy of high-dose cotrimoxazole therapy in terms of duration of hospital stays and reduction in mortality in severe COVID-19 infections. Methods: From May to November 2021, we conducted a double blind randomised controlled trial with two parallel groups in the COVID units of Bangabandhu Sheikh Mujib Medical University and Anwar Khan Modern Medical College Hospital, Dhaka. One group received standard therapy in addition to an oral dose of 960 mg of cotrimoxazole twice daily for 7 days (intervention group), while the other group received standard treatment and a placebo (standard group). Pre-protocol analysis was done. Results: A total of 188 patients were enrolled, but 166 completed the study. Of them, 93 were in the intervention group and 73 were in standard group. The mean ages of the groups were similar (intervention, 56.2 and standard, 59.2 years) (P=0.10). The mortality at 28 days between groups was also similar (11.8% in the intervention group and 15.0% in the standard group) (P=0.56). The hospital stay was 13.7 days for the intervention group and 13.5 days for the standard group (P=0.86). However, the reduction in C-reactive protein was statistically significant in the intervention group, with a mean decline of 23.6 mg/L (95% confidence interval, 0.5–46.7 mg/L). Conclusion: High-dose cotrimoxazole did not benefit in shortening in-hospital stay or reducing mortality at day 28 in patients with severe COVID-19. However, the decline in the C-reactive protein level was significant, necessitating further research.

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 registrationNCT02140255.

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]

Cerebral melioidosis is a rare entity which is minimally reported in literature, having multiple diagnostic challenges as it mimics most of the other diseases of the central nervous system (CNS). Spectrum of CNS melioidosis depends on the entry of the organism and immune status of the patient. Due to the delay in diagnosis, it has a high morbidity and mortality. It is thought to be a disease of the immunocompromised with risk of exposure to soil or surface water. We present a case of an immunocompetent patient without any known risk factors for significant exposure, who presented with fever and rapidly progressive multiple cranial nerve palsies followed by reduced level of consciousness and cerebellar signs. She was eventually diagnosed to have encephalomyelitis, a form of neuro melioidosis, with radiological evidence of acute demyelinating encephalomyelitis, and successfully treated with parenteral meropenem for intensive phase and cotrimoxazole for a long eradication phase. High index of suspicion and early initiation of treatment with suitable antibiotics for an optimal duration, evidenced complete recovery.

Cotrimoxazole, the combined formulation of sulfamethoxazole and trimethoprim, is one of the treatments of choice for several infectious diseases, particularly urinary tract infections. Both components of cotrimoxazole are synthetic antimicrobial drugs, and their combination was introduced into medical therapeutics about half a century ago. In Gram-negative bacteria, resistance to cotrimoxazole is widespread, being based on the acquisition of genes from the auxiliary genome that confer resistance to each of its antibacterial components. Starting from previous knowledge on the genotype of resistance to sulfamethoxazole in a collection of cotrimoxazole resistant uropathogenic Escherichia coli strains, this work focused on the identification of the genetic bases of the trimethoprim resistance of these same strains. Molecular techniques employed included PCR and Sanger sequencing of specific amplicons, conjugation experiments and NGS sequencing of the transferred plasmids. Mobile genetic elements conferring the trimethoprim resistance phenotype were identified and included integrons, transposons and single gene cassettes. Therefore, strains exhibited several ways to jointly resist both antibiotics, implying different levels of genetic linkage between genes conferring resistance to sulfamethoxazole (sul) and trimethoprim (dfrA). Two structures were particularly interesting because they represented a highly cohesive arrangements ensuring cotrimoxazole resistance. They both carried a single gene cassette, dfrA14 or dfrA1, integrated in two different points of a conserved cluster sul2-strA-strB, carried on transferable plasmids. The results suggest that the pressure exerted by cotrimoxazole on bacteria of our environment is still promoting the evolution toward increasingly compact gene arrangements, carried by mobile genetic elements that move them in the genome and also transfer them horizontally among bacteria.

A sudden emergence of Stenotrophomonas maltophilia as 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.

This bioequivalence study was conducted to evaluate two oral formulations of cotrimoxazole tablets in healthy Chinese subjects. All 26 subjects recruited to this study were randomly and evenly classified into two groups and received a single dose (sulfamethoxazole: 400 mg and trimethoprim: 80 mg) of test cotrimoxazole tablets (generic drug) or reference cotrimoxazole tablets (branded drug). After a 7-day washout period, these subjects received one dose of reference drug or test drug. Blood samples were collected from participants before and up to 48 h after dosing to assess the concentration of sulfamethoxazole (SMX) and trimethoprim (TMP) in plasma and a plasma concentration-time curve was drawn. Then, the pharmacokinetics parameters were calculated accordingly. Our data revealed that there were no significant differences observed in the maximum plasma concentration (Cmax), area under the curve from time 0 to the last measurable concentration (AUC0-t), and area under the curve from time 0 to infinity (AUC0-∞) between the two formulations. For SMX, the 90% confidence intervals (CI) of the geometric mean ratio for Cmax, AUC0-t, and AUC0-∞ were 104.03-113.92%, 100.46-103.70%, and 100.41-103.81%, respectively. Similarly, for Trimethoprim (TMP), the 90% CI ranged from 98.54 to 106.95% for Cmax, from 99.31 to 107.68% for AUC0-t, and from 99.49 to 107.55% for AUC0-∞. Importantly, all these 90% CI values fell within the range of 80.00–125.00%, indicating that the test drug is bioequivalent to the reference drug. Furthermore, throughout the entire trial, no suspected serious adverse events were reported, indicating the safety profile of the newly developed generic cotrimoxazole. In summary, our study demonstrates that the newly developed generic formulation of cotrimoxazole is bioequivalent to the branded formulation under fasting conditions. [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]

The combination of trimethoprim and sulfamethoxazole as a fixed-dose combination in the ratio 1:5 is known as cotrimoxazole. It is used as antibiotic to treat a variety of bacterial infections. Cotrimoxazole is part of the World Health Organization's list of essential medicines. Cotrimoxazole is an example of a drug that was partially unavailable in Germany during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the Ukraine war. The dependency on foreign sources of medicines is well known in Europe and resulted in the Pharmaceutical Strategy for Europe 2020, a strategy concept "will support the competitiveness and innovative capacity of the EU's pharmaceutical industry". High-performance thin-layer chromatography (HPTLC) is a cost-effective method for quantifying pharmaceutically active compounds. Diode-array detection (DAD) in conjunction with HPTLC can simultaneously detect ultraviolet‒visible (UV‒VIS) and fluorescence spectra directly from the plate. Visualization as a contour plot helps to identify the optimal wavelengths for compound quantification and reduce uncertainty in the determination. The quantification of trimethoprim and sulfamethoxazole is presented in a case study that highlights the key aspects for HPTLC quantification of pharmaceutical fixed-dose combinations with minimal uncertainty. HPTLC‒DAD allows quantification of trimethoprim and sulfamethoxazole with a required relative standard deviation of less than 2.5%. [ABSTRACT FROM AUTHOR]

BackgroundPediatric 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.MethodsA 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.ResultsRoutine 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

Stenotrophomonas maltophilia is an opportunistic, multidrug-resistant non-fermentative Gram-negative bacillus, posing a significant challenge in clinical treatment due to its numerous intrinsic and acquired resistance mechanisms. This study aimed to evaluate the adequacy of antibiotics used for the treatment of S. maltophilia infections in critically ill patients using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The antibiotics studied included cotrimoxazole, levofloxacin, minocycline, tigecycline, cefiderocol, and the new combination aztreonam/avibactam, which is not yet approved. By Monte Carlo simulations, the probability of target attainment (PTA), the PK/PD breakpoints, and the cumulative fraction of response (CFR) were estimated. PK parameters and MIC distributions were sourced from the literature, the European Committee on Antimicrobial Susceptibility Testing (EUCAST), and the SENTRY Antimicrobial Surveillance Program collection. Cefiderocol 2 g q8h, minocycline 200 mg q12h, tigecycline 100 mg q12h, and aztreonam/avibactam 1500/500 mg q6h were the best options to treat empirically infections due to S. maltophilia. Cotrimoxazole provided a higher probability of treatment success for the U.S. isolates than for European isolates. For all antibiotics, discrepancies between the PK/PD breakpoints and the clinical breakpoints defined by EUCAST (or the ECOFF) and CLSI were detected.

Introduction: Salmonella typhi is a large group of gram-negative bacilli with Enterobacteriaceae and common pathogens between humans and animals, which is the main cause of typhoid fever in humans. One of the most common antibiotics in the treatment of Salmonella is cotrimoxazole, but due to the widespread use of antibiotics, bacterial resistance has developed. The aim of this study was to investigate the antibacterial effect of silver nanoparticles and its combination with the antibiotic cotrimoxazole to produce a more effective antimicrobial drug against Salmonell typhi. Methods: In this experimental study, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for silver nanoparticles and combination with cotrimoxazole, was performed based on microdilution method. Then, their antibacterial effects were investigated in infected mouse model. In order to analyze the results statistically, SPSS software version 16 was used. In this test, P< 0.05 was considered as a significant level. Results: MIC and MFC of silver nanoparticles for Salmonella typhi were 4 ppm and 8 ppm respectively, composition of silver nanoparticles with cotrimoxazole for Salmonella typhi were 62 ppm and 125 ppm and cotrimoxazole for Salmonella typhi were 500 ppm and 1000 ppm. Mouse model to study the antibacterial effect of silver nanoparticles and combination with cotrimoxazole against Salmonella typhi infection was confirmed., Silver nanoparticles had the highest antibacterial effect and cotrimoxazole has the lowest antibacterial effect than other groups. Conclusion: Silver nanoparticles are very effective compared to other groups, especially the antibacterial cotrimoxazole.

Abstract 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.

Hombre de 34 años que presenta infecciones urológicas recurrentes tratado con diferentes antibióticos como consecuencia de estenosis uretral, se ha sometido a varias intervenciones quirúrgicas desde 2018. Algunos episodios de infección cursan con dolor muy intenso y otros son asintomáticos. En diciembre de 2021 aparece por primera vez fiebre alta, cefalea muy intensa y dolor muscular por lo que se confundieron los síntomas con COVID-19. Cuando aparecieron estos síntomas, el paciente llevaba siendo tratado 8 días con Trimetoprim/sulfametoxazol 160/800 mg. Tras pruebas de COVID-19 negativas, deciden hospitalizar al paciente en urología y determinan que los síntomas se deben a la infección urológica. Le diagnostican además miocarditis y neuropatía periférica. Durante los siguientes meses el paciente vuelve a tener urocultivos positivos para diferentes bacterias y es tratado con otros antibióticos. En mayo de 2022, tras positivo para Escherichia coli le prescriben Trimetoprim/sulfametoxazol 160/800 mg. A los 2 días de iniciar el tratamiento es hospitalizado con fiebre muy alta, cefalea intensa y dolor lumbar y en las extremidades que le impide moverse, es derivado a traumatología y le diagnostican lumbalgia. Durante el segundo ingreso el paciente comenta el caso con su farmacéutica de confianza que conoce su historia clínica desde el inicio y haciendo un estudio se detecta que existe la posibilidad de que los cuadros agudos se deban a un efecto adverso del Trimetoprim/sulfametoxazol 160/800 mg. La farmacéutica notifica al paciente su sospecha que lo traslada a los médicos que lo tratan. Se incluye la información de la posible intolerancia/ alergia en la historia clínica del paciente.

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]

Introduction: AIDS patients are more susceptible to opportunistic diseases, such as toxoplasma encephalitis, because of weakened immune systems. Toxoplasma encephalitis manifests as a severe neurological crisis in HIV patients. The standard initial treatments are sulfadiazine and pyrimethamine. This case presents an HIV patient treated with an alternative regimen for toxoplasma encephalitis. Case description: A young Acehnese man, 32 years old, arrived at the emergency unit after complaining of a general seizure 2 hours before arrival. He has a history of a two-week fever and white patches on his tongue and oral cavity. The result of the HIV test was positive, and after a thorough examination, he was diagnosed with toxoplasma encephalitis. The patient was given cotrimoxazole 960 mg twice daily and clindamycin 600 mg four times daily as an alternative treatment. Clinical improvement was reported after six weeks of therapy. Conclusion: A case of toxoplasma encephalitis was reported. The first-line treatment for toxoplasma encephalitis is pyrimethamine and sulfadiazine; however, the patient was treated with cotrimoxazole and clindamycin as an alternative treatment. Clinical improvement was used to assess the success of therapy. Cotrimoxazole and clindamycin can be utilized as alternative regiment therapy if the first-line treatment option is unavailable.

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]

Allergic drug eruptions (ADE) remain a challenge in people living with HIV (PLWH), requiring more studies to guide clinical approaches. While cotrimoxazole is widely used as prophylaxis in PLWH, relationship between client characteristics toward the occurrence of cotrimoxazole ADEs is still poorly understood. A retrospective cohort study followed PLWH initiated with antiretroviral therapy (ART) in St. Carolus Hospital between January 2009 to December 2021. ADE occurrence due to cotrimoxazole were tested for significance using Pearson's Chi-square and Fisher's Exact Test (significant outcome measured as p < 0.05) against CD4 levels at very low (0-100 cells/ul) and low (101-200 cells/ul) groups, comorbidities, and retention status. Cotrimoxazole-related ADEs occurred in 258 (14%) of 1789 subjects with CD4 levels ≤200 cells/ul. Comorbidities of Hepatitis B, Hepatitis C, and M. tuberculosis infections were found in 11, 4, and 95 subjects respectively. 151 (59%) of ADE group had very low CD4 levels (p value > 0.05). No significant difference was found in ADE incidence between age groups, genders, CD4 levels, comorbidities, and ART retention. Cotrimoxazole-induced ADE is unrelated to CD4 levels, and ART retention was not affected. ADE severity ranges from mild to serious manifestations, and close monitoring is crucial to ensure ADEs are treated ART are well-maintained. [ABSTRACT FROM AUTHOR]

Background: Talaromyces marneffei (formerly Penicillium marneffei) is an important thermally dimorphic fungus endemic which is characterized by one of the most frequent opportunistic infections in HIV/AIDS patients, mainly prevalent in Southeast Asia, southern China, and northeastern India. Cotrimoxazole(CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi, thereby commonly used to prevent several opportunistic infections among HIV/AIDS patients. In addition to preventing other HIV-associated opportunistic infections, CTX prophylaxis are considered to have the potential to prevent T. marneffei infection in HIV/AIDS patients receiving antiretroviral therapy (ART). However, the effect of cotrimoxazole towards T. marneffei fungus in vitro remains unclear. Methods: Human THP-1 macrophages were used as cell model in vitro to explore the effect and mechanism of cotrimoxazole resistance towards T. marneffei. Cell viability assay and drug sensitivity colony forming units (CFU) experiments were conducted to determine the minimum inhibitory concentration (MIC) of cotrimoxazole inside and outside THP-1 macrophages respectively. Enzyme-linked immunosorbent assay (Elisa) was used to measure the concentration of Dihydropteroic acid synthetase (DHPS), Dihydrofolate synthetase (DHFS) and Dihydrofolate reductase (DHFR) between T. marneffei adding TMP/SMX and without adding TMP/SMX group respectively. Real-time fluorescence quantitative PCR(qPCR) was performed to detect the mRNA expression levels in Dectin-1 mediated signaling pathway and downstream inflammatory cytokines including IL-6, IL-10, IL-23A, CXCL8 and TNF-α released by T. marneffei-infected macrophages between adding TMP/SMX and without adding TMP/SMX group respectively. Results: Cotrimoxazole can inhibit the proliferation of T. marneffei within safe concentration inside and outside THP-1 macrophages. Drug susceptibility results showed the minimal inhibit concentration(MIC) of 1:5 TMP/SMX was ranging from 14/70 to 68/340 μg/ml. The MIC of SMX was ranging from 100 to 360 μg/ml. The MIC of TMP was ranging from 240 to 400 μg/ml outside macrophages. The MIC of TMP/SMX was ranging from 36/180 to 68/340 μg/ml. The MIC of SMX was ranging from 340 to 360 μg/ml. The MIC of TMP was ranging from 320 to 400 μg/ml inside macrophages. The synergistic interaction of 1:5 TMP/SMX was more effective in inhibiting T. marneffei than separate SMX and TMP. DHPS, DHFS and DHFR can be inhibited by cotrimoxazole within safe and effective concentration. Dectin-1 expression is increased following T. marneffei infection, leading to the increase of IL-6, IL-10, IL-23A and the decrease of CXCL8 and TNF-α. Conversely, cotrimoxazole decrease the levels of Dectin-1, IL-6, IL-10, IL-23A and increase the levels of CXCL8 and TNF-α, thereby enhancing the intracellular killing-T. marneffei capacity of macrophages. Conclusions: Our findings indicated that cotrimoxazole directly inhibited T. marneffei growth by blocking DHPS, DHFS and DHFR and indirectly inhibited T. marneffei growth perhaps by regulating the Dectin-1 signaling pathway, which may effectively interfere with the defense ability of the host against T. marneffei infection. [ABSTRACT FROM AUTHOR]

Toxoplasma infection can be congenital or acquired. Infection with Toxoplasma gondii can result in multi-organ involvement in immunocompromised patients; whereas in immunocompetent patients, it usually remains asymptomatic. Toxoplasma is a rare cause of isolated lymphadenopathy especially in immunocompetent individuals, though it is a common manifestation of this protozoal infection. We present a 27-year-old male who presented to us with isolated cervical lymphadenopathy. Histopathology and serological studies confirmed the diagnosis of toxoplasma lymphadenopathy. It usually affects the posterior cervical group of lymph nodes, but in our case, it had also affected anterior group and presented without any constitutional symptom. The patient was treated with cotrimoxazole double strength tablet once daily for 1 month and responded well.

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]

Abstract 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.

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]

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.

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]

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).

Emmanuel Lafont,1,* Pierre-Louis Conan,2,* Véronica Rodriguez-Nava,3 David Lebeaux4,5 1Department of Infectious Diseases and Tropical Medicine, Université de Paris, Necker-Enfants Malades University Hospital, Centre d’Infectiologie Necker-Pasteur, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris, France; 2Service de Maladies Infectieuses et Tropicales, Hôpital d’Instruction des Armées Bégin, Saint-Mandé, France; 3Research Group on Bacterial Opportunistic Pathogens and Environment UMR5557 Écologie Microbienne, French Observatory of Nocardiosis, Université de Lyon 1, CNRS, VetAgro Sup, Lyon, France; 4Université de Paris, Paris 75006, France; 5Service de Microbiologie, Unité Mobile d’Infectiologie, Hôpital Européen Georges Pompidou, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris 75015, France*These authors contributed equally to this workCorrespondence: David LebeauxService de Microbiologie, Unité Mobile d’Infectiologie, Hôpital Européen Georges Pompidou, Assistance Publique – Hôpitaux de Paris (AP-HP), 20 Rue Leblanc, Paris 75015, FranceTel +33 1 56 09 29 69Fax +33 1 56 09 24 46Email david.lebeaux@aphp.frAbstract: Nocardia spp. is an environmental filamentous Gram-positive bacterium that may cause infections in humans and, despite recent progress, many challenges remain regarding the management of nocardiosis. This review aims at describing most recently published data regarding the diagnosis, treatment and follow-up of patients with invasive nocardiosis. As nocardiosis mainly affects patients with cell-mediated immunity defects, a comprehensive workup is mandatory in case of invasive nocardiosis occurring in ”apparently healthy patients”. Indeed, invasive nocardiosis might reveal an unknown primary immunodeficiency or the presence of anti-GM-CSF autoantibodies. Even if the diagnosis of nocardiosis mostly relies on direct examination and bacterial culture, a genus-specific PCR may be used for the detection of Nocardia, when directly performed on a clinical sample. Brain imaging should always be performed, even in the absence of neurological symptoms. Cotrimoxazole (trimethoprim/sulfamethoxazole), linezolid, parenteral cephalosporins, carbapenems and amikacin may be used as initial antibiotics to treat nocardiosis. Cotrimoxazole or linezolid can be used as monotherapy in selected patients without brain involvement. Although treatment duration has historically been set to at least 6 months in the absence of central nervous system involvement, shorter durations (< 120 days) seem to be associated with a favourable outcome.Keywords: opportunistic infection, dissemination, anti-GM-CSF autoantibodies, brain imaging, molecular biology, antibiotic susceptibility testing, cotrimoxazole

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]

In the management of cystic fibrosis, treatments against Staphylococcus aureus and Haemophilus influenzae such as amoxicillin or cotrimoxazole have to be prescribed and the antibiotherapy's efficacy may be linked to the concentration that reaches the infected site. As cystic fibrosis patients present disturbed pharmacokinetics parameters, drug monitoring would be relevant to assess the lung distribution of antibiotics and to optimize dosing regimens. In this context, the aim of the study was to develop and validate HPLC‐based methods for the determination of both antibiotics in bronchial sputum from cystic fibrosis patients, in order to assess the distribution of the drugs into the lungs. Plasma proteins were precipitated by acetonitrile and amoxicillin concentrations in sputum were determined by HPLC coupled with tandem‐mass spectrometry. Following liquid extraction with ethyl acetate, cotrimoxazole was quantified by HPLC using ultraviolet detection. Both methods were rapid, specific, accurate and reproducible. The method was applied to patient samples. In three treated patients, concentrations of amoxicillin in sputum were similar and below the lower limit of quantification (0.1 μg/g) and in six patients, sputum concentrations up to 11.1 and 6.4 μg/g were measured for sulfamethoxazole and trimethoprim, respectively. [ABSTRACT FROM AUTHOR]

Resumen: Contexto: La OSIDebagoiena es una Organización Sanitaria Integrada (OSI) por un hospital y 4 Unidades de Atención Primaria (UAP) con un área de influencia de 67.000 habitantes. Problema local: Se revisó la utilización de los antibióticos en los pacientes con profilaxis antibiótica en una infección del tracto urinario (ITU): nitrofurantoína, fosfomicina trometamol, fosfomicina cálcica, cotrimoxazol y cefuroxima axetilo y se encontraron diversas incidencias respecto a la posología, la duración y la adecuación. Métodos: A partir de la base de datos Oracle Business Intelligence (OBI) se obtuvo el listado de los pacientes de la OSI que cumplían los criterios de ITU recurrente y, por otro lado, el de los pacientes con antibiótico en dosis profiláctica. Intervenciones: Se llevó a cabo un análisis estadístico descriptivo que se analizó y se plasmó en un informe de la situación de uso de la profilaxis de la ITU.Se impartieron sesiones en cada UAP y otra sesión general en el hospital para mostrar los resultados. Resultados: En la OSI con ese criterio se detectaron 382 pacientes, y de esos, 12 tenían profilaxis activa en marzo 2019 (330 mujeres y 52 hombres).Además, se realizó una búsqueda por antibiótico y prescripción crónica y «a demanda», y se comprobó que existían muchos más pacientes con profilaxis antibiótica.En las sesiones se aclaran los conceptos en torno a los antibióticos que se pueden utilizar en profilaxis ITU, la posología, la duración, etc. Cualitativamente, han aumentado sensiblemente las prescripciones a demanda con limitación de envases. Conclusiones: Las medidas consensuadas se recogieron en un protocolo de utilización de profilaxis ITU a nivel de OSI consensuado entre Atención Primaria (AP)-Comisión de infecciones y urología. Abstract: Context: OSI Debagoiena Integrated Healthcare Organization is composed of a hospital and 4 Primary Care Units (PCU) with an area of influence of 67,000 inhabitants. Local problem: The use of antibiotics was reviewed in patients with antibiotic prophylaxis in urinary tract infection (ITU): Nitrofurantoin, fosfomycin trometamol, calcium fosfomycin, cotrimoxazole and cefuroxima axethyl and various incidences regarding dosage, duration and adequacy were found. Methods: From the Oracle Business Intelligence (OBI) database, the list of patients meeting the recurrent UTI criteria and, on the other hand, patients with antibiotics in prophylactic doses were obtained. Interventions: A descriptive statistical analysis was carried out which was analyzed and included in a report on the status of use of ITU prophylaxis.Sessions were held at each PCU and another general session at the hospital to show the results. Results: In the Organization, with this criterion, 382 patients were detected, and of these, 12 were active prophylaxis in March 2019 (330 women, 52 men).In addition, an antibiotic and chronic and “on-demand” prescription search was conducted and many more patients with antibiotic prophylaxis were found to exist.The sessions clarify concepts around antibiotics that can be used in ITU prophylaxis, posology, duration, etc. Qualitatively, on-demand requirements with packaging limitation have increased significantly. Conclusions: Consensus measures were collected in a protocol for the use of prophylaxis of UTI at the Organization level agreed between Primary care, Infection Commission and Urology.

Objective: This study aimed to assess the overall antibiotic susceptibility of Cutibacterium acnes (C. acnes), a bacterium implicated in acne vulgaris, with a particular focus on clindamycin and fluoroquinolones, which are commonly used in inflammatory acne treatment., Methods: A systematic search of Scopus, PubMed, Web of Science and EMBASE databases was conducted to identify relevant studies. Pooled prevalence estimates were calculated using a random-effects model, and additional analyses included quality assessment, evaluation of publication bias, meta-regression and subgroup analyses based on antimicrobial susceptibility methods and year of publication., Results: The analysis incorporated a total of 39 studies. The random-effects model revealed that the proportion of clindamycin-resistant isolates was 0.031 (95% CI: 0.014-0.071). Additionally, macrolides, including erythromycin (0.366; 95% CI: 0.302-0.434) and azithromycin (0.149; 95% CI: 0.061-0.322), exhibited distinct prevalence rates. Tetracyclines, including doxycycline (0.079; 95% CI: 0.014-0.071), tetracycline (0.062; 95% CI: 0.036-0.107) and minocycline (0.025; 95% CI: 0.012-0.051), displayed varying prevalence estimates. Fluoroquinolones, including ciprofloxacin (0.050; 95% CI: 0.017-0.140) and levofloxacin (0.061; 95% CI: 0.015-0.217), demonstrated unique prevalence rates. Additionally, the prevalence of the combination antibiotic trimethoprim/sulfamethoxazole (SXT) was estimated to be 0.087 (95% CI: 0.033-0.208)., Conclusion: The study findings highlight a concerning increase in antimicrobial-resistant C. acnes with the use of antibiotics in acne treatment. The strategic utilization of appropriate antimicrobials has emerged as a crucial measure to mitigate the emergence of antimicrobial-resistant skin bacteria in acne management., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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]