Genetics of resistance to trimethoprim in cotrimoxazole resistant uropathogenic Escherichia coli: integrons, transposons, and single gene cassettes.

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.

Optimizing Antibiotic Therapy for Stenotrophomonas maltophilia Infections in Critically Ill Patients: A Pharmacokinetic/Pharmacodynamic Approach.

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.

The prevention of congenital toxoplasmosis using a combination of Spiramycin and Cotrimoxazole: The long-time experience of a tertiary referral centre.

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.

Nebulised pentamidine prophylaxis of pneumocystis pneumonia in adults accessing HIV services at royal free hospital, London.

Receipt of nebulised pentamidine in people with HIV was audited to identify if individuals were appropriately receiving nebulised pentamidine, and whether national guidelines were being followed when prophylaxis was commenced and discontinued. Of 76 people with who received nebulised pentamidine, the main indication for starting nebulised pentamidine was a co-trimoxazole adverse drug reaction. Co-trimoxazole desensitization was not attempted before starting nebulised pentamidine. The main indication for stopping nebulised pentamidine prophylaxis was when immune reconstitution occurred. This single centre audit revealed that national guidelines were being followed in most cases. The lack of information regarding the reason for starting or stopping nebulised pentamidine prophylaxis, or detail of the clinician's concerns about potential poor adherence with oral regimens of prophylaxis as a reason for choosing nebulised pentamidine prophylaxis, identifies a need for improved documentation of clinicians' decision-making. Introduction of pharmacist-led interventions/alerts using patients' electronic records, similar to those used in primary care, would enable the specialist pharmacy team to identify when and if co-trimoxazole desensitization has been offered and discussed/declined before a clinician prescribes nebulised pentamidine as well as enabling identification of those in who pentamidine prophylaxis has been continued, despite "immune reconstitution".

Cotrimoxazole and targeted antibiotic prophylaxis for transrectal prostate biopsy: a single-center study.

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.

Listeria monocytogenes Infections in Hematopoietic Cell Transplantation Recipients: Clinical Manifestations and Risk Factors. A Multinational Retrospective Case-Control Study from the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation.

Listeriosis is rare after hematopoietic stem cell transplantation (HCT). Little is known about listeriosis in this population. In this retrospective international case-control study, we evaluated 41 listeriosis episodes occurring between 2000 and 2021 in HCT recipients (111 transplant centers in 30 countries) and assessed risk factors for listeriosis by comparisons with matched controls. The 41 listeriosis episodes (all due to Listeria monocytogenes [LM]) occurred in 30 allogeneic (allo)-HCT recipients and 11 autologous (auto)-HCT recipients at a median of 6.2 months (interquartile range [IQR], 1.6 to 19.3 months) post-HCT. The estimated incidence was 49.8/100,000 allo-HCT recipients and 13.7/100,000 auto-HCT recipients. The most common manifestations in our cohort were fever (n = 39; 95%), headache (n = 9; 22%), diarrhea, and impaired consciousness (n = 8 each; 20%). Four patients (10%) presented with septic shock, and 19 of 38 (50%) were severely lymphocytopenic. Thirty-seven patients (90%) had LM bacteremia. Eleven patients (27%) had neurolisteriosis, of whom 4 presented with nonspecific signs and 5 had normal brain imaging findings. Cerebrospinal fluid analysis revealed high protein and pleocytosis (mainly neutrophilic). Three-month mortality was 17% overall (n = 7), including 27% (n = 3 of 11) in patients with neurolisteriosis and 13% (n = 4 of 30) in those without neurolisteriosis. In the multivariate analysis comparing cases with 74 controls, non-first HCT (odds ratio [OR], 5.84; 95% confidence interval [CI], 1.10 to 30.82; P = .038); and lymphocytopenia <500 cells/mm3 (OR, 7.54; 95% CI, 1.50 to 37.83; P = .014) were significantly associated with listeriosis. There were no statistically significant differences in background characteristics, immunosuppression, and cotrimoxazole prophylaxis between cases and controls. HCT recipients are at increased risk for listeriosis compared to the general population. Listeriosis cause severe disease with septic shock and mortality. Neurolisteriosis can present with nonspecific signs and normal imaging. Lymphocytopenia and non-first HCT are associated with an increased risk of listeriosis, and cotrimoxazole was not protective.

Pharmacokinetics and bioequivalence evaluation of two oral formulations of cotrimoxazole tablets in healthy Chinese volunteers under fasting conditions.

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.

First Case of Nocardia wallacei From India: A Case Report and Literature Review.

Nocardia is a type of bacteria that can cause infections in both immunocompromised and immunocompetent hosts. It is an obligate aerobe and is commonly found in the environment. Pulmonary nocardiosis may present as pneumonia, endobronchial inflammatory masses, lung abscess, and cavitary disease with contiguous extension, leading to effusion and empyema. We present a case of pulmonary nocardiosis in a 75-year-old male patient with type 2 diabetes mellitus. The patient presented with bilateral pneumonia and hypoxia with an oxygen saturation of 85%. Sputum samples were sent to the microbiology laboratory for testing. Acid-fast staining with 1% H2SO4 showed acid-fast branching filamentous rods, but Nocardia could not be isolated in culture. The sample was subjected to 16S rRNA gene sequencing, which identified the pathogen as Nocardia wallacei. The culture of the sputum did not grow any pathogenic organisms, and the blood culture was sterile. Unfortunately, the patient left the hospital against medical advice as he was advised for intubation. The patient could not survive and died the next day after leaving the hospital. N. wallacei can be fatal and cause disseminated infection in both immunosuppressed and immunocompetent patients. Only eight case reports of N. wallacei have been reported in the literature from various parts of the world. Our case is the first case report of N. wallacei from India.

A Fatal Case of Multidrug-Resistant Pleural Nocardiosis by Nocardia otitidiscaviarum in an Immunosuppressed Patient: A Case Report and Literature Review.

Nocardiosis is known as an opportunistic infection in immunocompromised hosts. We present to you a case of pleural nocardiosis in a 38-year-old male patient who was a chronic smoker and presented with a left-sided pleural effusion. He was a known case of thrombocytopenia due to immune thrombocytopenia (ITP) and was on steroid therapy. On admission, he was found to be positive for HIV. Pleural fluid was sent to microbiology, where acid-fast staining with 1% sulfuric acid (H2SO4)showed acid-fast branching filamentous rods and cultures grew Nocardia, which was resistant to ampicillin, ceftriaxone, imipenem, cotrimoxazole, erythromycin, tetracycline, and susceptible to amikacin, linezolid, and levofloxacin. The isolate was identified as Nocardia otitidiscaviarum using 16S rRNA gene sequencing. Culture from the chest wall drain grew Escherichia coli and Stenotrophomonas maltophilia. Subsequently, the patient developed sepsis, and paired blood cultures grew Candida guilliermondii. Unfortunately, the patient could not survive despite aggressive efforts and died after 40 days of admission.

Antibiotic prophylaxis in immunosuppressed patients - Missed opportunities from trimethoprim-sulfamethoxazole allergy label.

Trimethoprim-sulfamethoxazole (TMP-SMX) is a broad spectrum antibiotic in use for more than 50 years. It has an important indication as first line agent in the prophylaxis of opportunistic infections, particularly Pneumocystis jirovecii pneumonia (PJP), in immunosuppressed patients. For those who have a history of allergy or severe intolerance to TMP-SMX, pentamidine, dapsone or atovaquone may be substituted; however there is evidence that TMP-SMX offers superior coverage for PJP, toxoplasmosis, and nocardiosis. Compared to pentamidine, it has the added benefit of cost-effectiveness and self-administration as opposed to required hospital attendance for administration. Many patients who report a history of allergy or adverse reaction to TMP-SMX (or "sulfur allergy") will be found not to be allergic; and even those who are allergic may be able to be desensitized. The evaluation and, where appropriate, removal of TMP-SMX allergy label enables the use of TMP-SMX for prophylaxis against opportunistic infections. This is a cost-effective intervention to optimize antimicrobial prescribing and reduce the risk of opportunistic infections in immunosuppressed patients.

Pneumocystosis in a patient with rheumatoid arthritis on adalimumab therapy: a case-based review.

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.

Drug-induced secondary haemophagocytic lymphohistiocytosis in hairy cell leukaemia.

Haemophagocytic lymphohistiocytosis (HLH) is a rare, aggressive, excess immune activation syndrome. Diagnosis can be challenging due to its several clinical mimics including sepsis. There are multiple aetiologies of HLH; in adults, it is most commonly triggered by infection, malignancy, drugs and autoimmune processes. Failure to rapidly diagnose and treat this condition can be fatal. The management of HLH includes identifying and removing the trigger, supportive management and immunosuppression. Identifying the trigger is essential to inform the most appropriate type of immunosuppression. Here, we report a case of likely drug-induced HLH in a patient recently treated for hairy cell leukaemia. The culprit drug was thought to be co-trimoxazole and this case report highlights a very rare complication of this commonly used drug. We discuss our management approach with steroid monotherapy and withdrawal of co-trimoxazole.

Myelotoxicity and kidney dysfunction related to the use of trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia: a case report of severe adverse events with a common drug

ABSTRACT Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary therapeutic option for Pneumocystis jirovecii pneumonia (PCP). Gastrointestinal symptoms and cutaneous rash are common side effects, with hyperkalemia being uncommon in patients without kidney dysfunction, and myelotoxicity being even rarer. We present the case of a male patient with hypertension and a recent diagnosis of non-Hodgkin lymphoma, undergoing rituximab treatment for two months. He was admitted to the intensive care unit due to dyspnea, tachypnea, and pleuritic pain, requiring mechanical ventilation. Chest computed tomography showed bilateral and multilobed ground-glass opacities, compromising more than 80% of the lung parenchyma. Pulmonary tuberculosis and COVID-19 were ruled out. An angiotomography and Doppler ultrasound revealed an extensive pulmonary thrombus and deep venous thrombosis. Empiric treatment with TMP-SMX for PCP was initiated, but within four days, the patient experienced metabolic acidosis and severe hyperkalemia, necessitating hemodialysis. He also presented with progressive pancytopenia and critical levels of leukopenia and thrombocytopenia. The hypothesis of TMP-SMX-induced myelotoxicity was suspected. Considering the unavailability of an alternative treatment, it was opted to continue TMP-SMX and initiate a granulocyte-colony-stimulating factor. However, the patient maintained medullary deterioration, becoming refractory to the transfusion of blood derivates. On the 17th day of treatment, a clinical decision was made to suspend TMP-SMX, leading to improvements within 48 hours in marrow and kidney functions, metabolic acidosis, and hyperkalemia. Despite all efforts, the patient died after 35 days of hospitalization due to hospital-acquired infections. This case highlights the importance of clinicians recognizing potential myelotoxicity with TMP-SMX and promptly discontinuing the drug if necessary.

Effect of co-trimoxazole and N-acetylcysteine alone and in combination on bacterial adherence on ureteral stent surface.

To assess the effect of co-trimoxazole and N-acetylcysteine (NAC), alone and in combination, on bacterial adherence to biofilm formed on ureteral stent surfaces. This prospective randomized study was conducted on 636 patients who underwent double J ureteral stent insertion after variable urological procedures. Patients were randomized into four groups: A (n = 165), no antibiotics or mucolytics during stent indwelling; B (n = 153), oral NAC (200 mg/day for children aged < 12 years old and 600 mg/day for adults) during stent indwelling; C (n = 162), oral co-trimoxazole (2 mg TMP/kg/day) during stent indwelling; and D (n = 156), both oral NAC and co-trimoxazole during stent indwelling. Two weeks following double J stent (JJ stent) insertion, urinalysis was performed on all patients and urine culture was done for all the patients at the day of double J stent removal. The stent was removed 2 weeks postoperatively, and a stent segment sized 3-5 cm from the bladder segment of the stent was sent for culture. Positive stent cultures were found in 63.6% (105/165), 43.1% (66/153), 37% (60/162), and 19.2% (30/156) patients of groups A, B, C, and D, respectively. E. coli was the organism most commonly isolated from the stent culture in all groups. The combination of co-trimoxazole and NAC was more effective in reducing bacterial adherence on ureteral stent surfaces than either alone.

Development of neutropenic sepsis during the eradication phase with co-trimoxazole in patients with melioidosis: two case reports.

Introduction: Burkholderia pseudomallei is the bacterium that causes melioidosis. It is mostly a tropical disease, and particularly common in Southeast Asia and northern Australia. The intensive intravenous phase and the oral prolonged eradication phase are the two phases of melioidosis treatment. The current recommended treatment for melioidosis eradication is oral co-trimoxazole (TMP/SMX). Case report: Two patients were diagnosed with B. pseudomallei bacteremia without a focus and were treated with oral TMP/SMX with folic acid during the eradication phase. Both presented with neutropenic sepsis with pneumonia and pyelonephritis at days 48 and 45 following TMP/SMX 320/1600 mg q12h (4 tablets) and in both of them, the folic acid compliance was poor. One patient died and the other survived following intensive treatment for neutropenia. At the presentation following neutropenic sepsis among both patients, the red blood cells and platelets were within normal limits. Both patients were on a high dose of TMP/SMX, as both were within 40-60 kg of body weight the ideal TMP/SMX dose would be 240/1200 mg q12h (3 tablets). Pancytopenia caused by TMP/SMX can frequently develop gradually over time. Alternately, it can develop rapidly and swiftly escalate to fulminant sepsis, disseminated intravascular coagulation, and fast hemolysis. However, the development of isolated neutropenia is rarely described in the literature. Conclusions: Prolonged use of TMP/SMX is important to eradicate B. pseudomallei and always the possibility of rare adverse effects has to be considered. Always weight-based TMP-SMX dosing has to be encouraged with need to ensure the compliance of folic acid. During the eradication phase, continuous monitoring of blood cell lines with weekly full blood count would be essential to identify neutropenia in advance.

Evaluation of Weight-Based Co-trimoxazole Dosing in a Saudi Tertiary Hospital.

BACKGROUND: Infections caused by Stenotrophomonas maltophilia (S. maltophilia) and Pneumocystis jirovecii (Pneumocystis jirovecii pneumonia (PJP)) require weight-based dosing for co-trimoxazole. The aim of this study is to assess the appropriateness of co-trimoxazole dosing in adult inpatients for the treatment of these infections. METHODOLOGY: This is a single-center, cross-sectional study that included adult inpatients treated with co-trimoxazole for a weight-based dose indication (S. maltophilia and PJP). The primary outcome was the appropriateness of co-trimoxazole dosing for these infections. RESULTS: Forty-three patients were included in the study. Of the 43 patients, 29 (67.4%) were using co-trimoxazole for PJP treatment, and 14 (32.6%) were using it for S. maltophilia treatment. The co-trimoxazole dose was appropriate in 22 (51.2%) patients, 21 (72.4%) in the PJP treatment group, and one (7.1%) in the S. maltophilia treatment group. Underdosing was observed in 21 (48.8%) patients, of whom eight (27.6%) were in the PJP treatment group and 13 (92.9%) were in the S. maltophilia treatment group. CONCLUSIONS: This study found a relatively high rate of underdosing of co-trimoxazole based on weight in hospitalized adults with PJP and S. maltophilia infections.

Genotypic and Phenotypic Characteristics of Co-Trimoxazole-Induced Cutaneous Adverse Reactions.

BACKGROUND: Co-trimoxazole has been reported as a common culprit drug for various cutaneous adverse drug reactions (CADRs). However, information on genotypic and phenotypic characteristics is still limited. We aimed to study clinical characteristics, genetic suitability, laboratory findings, and treatment outcomes in patients with co-trimoxazole-induced CADR and determine variables associated with severe cutaneous adverse reactions (SCARs). METHODS: The medical records of all patients diagnosed with co-trimoxazole-induced CADR during October 2015 and October 2021 were reviewed. Clinical characteristics and laboratory investigation with an emphasis on human leukocyte antigen (HLA) class I and HLA-DRB1 results linked to subtypes of cutaneous adverse reactions were evaluated. RESULTS: Seventy-two patients diagnosed with co-trimoxazole-induced CADR were included in the study. Mean age at diagnosis was 38.0 ± 14.6 years old, and 72% were female. Subtypes of reactions included maculopapular eruption (MPE; 56.9%), drug reaction with eosinophilia and systemic symptoms (DRESS; 23.6%), Stevens-Johnson syndrome (SJS; 12.5%), fixed drug eruption (4.2%), and urticaria (2.8%). Characteristics that were significantly associated with SCARs included male gender (OR = 3.01, 95% CI: 1.04-8.75), HIV infection (OR = 3.48, 95% CI: 1.13-10.75), prophylactic use of co-trimoxazole (OR = 4.89, 95% CI: 1.54-15.57), and co-trimoxazole administration longer than 10 days (OR = 7.65, 95% CI: 2.57-22.78). HLA-B*38:02 was associated with co-trimoxazole-induced SJS, while HLA-A*11:01, HLA-B*13:01, and HLA-DRB1*12:01 were associated with co-trimoxazole-induced DRESS. HLA-B*52:01 was associated with co-trimoxazole-induced MPE. CONCLUSIONS: Co-trimoxazole could induce various phenotypes of CADRs. Genotypic and phenotypic factors that may potentially predict co-trimoxazole-induced SCARs include male gender, HIV infection, prophylactic and prolonged drug use, as well as the presence of HLA-A*11:01, HLA-B*13:01, HLA-B*38:02, or HLA-DRB1*12:01 alleles.

Cost-effectiveness analysis of HLA-B*13:01 screening for the prevention of co-trimoxazole-induced severe cutaneous adverse reactions among HIV-infected patients in Thailand.

Studies found a strong association between HLA-B*13:01 allele and co-trimoxazole-induced severe cutaneous adverse reactions (SCARs). Genetic screening before initiation of co-trimoxazole may decrease the incidence of co-trimoxazole-induced SCARs. This study aims to evaluate the cost-effectiveness of HLA-B*13:01 screening before co-trimoxazole initiation in HIV-infected patients in Thailand. A combination of a decision tree model and a Markov model was used to estimate lifetime costs and outcomes of two strategies including 1) HLA-B*13:01 screening before co-trimoxazole initiation and 2) usual practice from a societal perspective. Alternative drugs are not considered because dapsone (the second-line drug) also presents a genetic risk. Input parameters were obtained from literature, government documents, and part of the TREAT Asia HIV Observational Database (TAHOD). One-way sensitivity analyses and probabilistic analyses were performed to determine robustness of the findings. HLA-B*13:01 screening resulted in 0.0061 quality-adjusted life years (QALYs) loss with an additional cost of 370 THB ($11.84). At the cost-effectiveness threshold of 160,000 THB ($5,112.85), the probability of the genetic screening strategy being cost-effective is 9.54%. This analysis demonstrated that HLA-B*13:01 allele screening before initiation of co-trimoxazole among HIV-infected patients is unlikely to be cost-effective in Thailand. Our findings will help policymakers make an evidence-informed decision making.

Impact of thrice-weekly cotrimoxazole prophylaxis on creatinine and potassium plasma levels in kidney transplant recipients.

INTRODUCTION: Cotrimoxazole (CTX) 800/160 mg daily or thrice-weekly is recommended as prophylaxis of Pneumocystis jirovecii pneumonia in kidney transplant recipients. Cotrimoxazole 800/160 daily elevates plasma creatinine and potassium levels but whether the thrice-weekly regimen does so is unknown. METHODS: Medical records of 225 kidney transplant recipients at Cliniques Universitaires Saint-Luc were analyzed retrospectively. All received thrice-weekly CTX 800/160 for 6 months after transplantation. Monthly laboratory results, co-medications, and tacrolimus trough levels were compared. Standard statistical tests were used. RESULTS: One month after CTX stop, creatinine level decreased by 0.11 mg/dl (8%, p = 0.029). This contrasts with its stability in previous and subsequent months. No co-medication change accounted for this decrease. The decrease averaged 0.17 mg/dl (p < 0.01) in the highest initial creatinine tertile. The higher the initial creatinine level, the greater the decrease after CTX stop (p < 0.001), and urea levels remained stable after CTX stop. Potassium levels decreased by 0.09 mmol/L (p = 0.021) one month after CTX stop, and decreased by 0.23 mmol/L (p < 0.01) in the highest initial potassium level tertile. CONCLUSIONS: Our study pinpoints the impact of CTX 800/160 thrice-weekly on creatinine and potassium levels in kidney transplant recipients. This should be considered when interpreting the evolution of plasma creatinine over time, especially in patients with graft dysfunction. Thus, creatinine levels of cohorts with 6 months versus lifelong CTX require different interpretations.