Patch testing in non-immediate hypersensitivity to cotrimoxazole: Is it useful?

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.

Brief communication: reasons for non-adherence of co-trimoxazole prophylaxis therapy among people living with HIV in a resource-limited setting, Northern Ethiopia.

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.

Prevalence of antibiotic-resistant Cutibacterium acnes (formerly Propionibacterium acnes) isolates, A systematic review and meta-analysis.

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.

The novel MFS efflux pump SxtP, regulated by the LysR-type transcriptional activator SxtR, is involved in the susceptibility to sulfamethoxazole/trimethoprim (SXT) and the pathogenesis of Acinetobacter baumannii.

Acinetobacter baumannii is a notorious opportunistic pathogen responsible for healthcare-associated infections worldwide. Efflux pumps play crucial roles in mediating antimicrobial resistance, motility, and virulence. In this study, we present the identification and characterization of the new A. baumannii efflux pump SxtP belonging to the MFS superfamily (major facilitator superfamily), along with its associated activator LysR-type transcriptional regulator (LTTR) SxtR, demonstrating their roles in sulfamethoxazole/trimethoprim (also known as co-trimoxazole or SXT) resistance, surface-associated motility and virulence.

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.

Prevalence of co-trimoxazole resistance among HIV-infected individuals in Ethiopia: a systematic review and meta-analysis.

Background: Co-trimoxazole is used as a prophylaxis for human immunodeficiency virus (HIV) patients to prevent opportunistic infections. Its widespread use results in the emergence of co-trimoxazole resistance, which is a significant problem. This systematic review and meta-analysis determined the pooled prevalence of co-trimoxazole resistance among HIV-infected individuals in Ethiopia. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was applied to report this study. The protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the assigned number CRD42024532240. Article search was performed using electronic databases such as PubMed, Medline, EMBASE, Google Scholar, Hinari, Web of Science, Science Direct, and African Journals Online. Data were extracted using a Microsoft Excel spreadsheet and analyzed using STATA version 11.0 software. A random-effects model was used to estimate the pooled effect size of co-trimoxazole resistance across studies with a 95% confidence interval. The heterogeneity was checked using I2 statistic. The presence of publication bias was determined using a funnel plot and Egger's test with a p-value <0.05 evidence of statistically significant bias. Subgroup and sensitivity analyses were performed. Results: Twenty-two studies with 5,788 HIV-infected individuals were included. The pooled prevalence of co-trimoxazole resistance was 61.73% (95% CI: 53.10-70.37%), with heterogeneity (I2 = 87.7%) and statistical significance (p < 0.001). A higher co-trimoxazole resistance was observed in HIV-infected individuals with urinary tract infection; 82.10% (95% CI: 75.03-89.17%). Among the bacterial spp., higher resistance to co-trimoxazole was observed in Escherichia coli; 70.86% (95% CI: 53.44-88.27%) followed by Salmonella spp.; 67.66% (95% CI: 41.51-93.81%) and Proteus spp.; 66.23% (95% CI: 34.65-97.82%). Conclusion: There is a higher prevalence of co-trimoxazole resistance in HIV-infected individuals in Ethiopia. This alarms WHO's recommendation of co-trimoxazole prophylaxis guidelines to review and update it. Additionally, a nationwide assessment of co-trimoxazole resistance in Ethiopia as a whole is required.Systematic review registration: identifier: CRD42024532240.

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".

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.

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.

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.

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.

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.

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.