Use Of Trimethoprim-sulfamethoxazole Research Articles

Molecular Analysis of Dihydropteroate Synthase Gene Mutations in Pneumocystis jirovecii Isolates among Bulgarian Patients with Pneumocystis Pneumonia

Pneumocystis jirovecii pneumonia (PCP) is a significant cause of morbidity and mortality in immunocompromised people. The widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment and prophylaxis of opportunistic infections (including PCP) has led to an increased selection of TMP-SMZ-resistant microorganisms. Sulfa/sulfone resistance has been demonstrated to result from specific point mutations in the DHPS gene. This study aims to investigate the presence of DHPS gene mutations among P. jirovecii isolates from Bulgarian patients with PCP. A total of 326 patients were examined via real-time PCR targeting the P. jirovecii mitochondrial large subunit rRNA gene and further at the DHPS locus. P. jirovecii DNA was detected in 50 (15.34%) specimens. A 370 bp DHPS locus fragment was successfully amplified in 21 samples from 19 PCP-positive patients, which was then purified, sequenced, and used for phylogenetic analysis. Based on the sequencing analysis, all (n = 21) P. jirovecii isolates showed DHPS genotype 1 (the wild type, with the nucleotide sequence ACA CGG CCT at codons 55, 56, and 57, respectively). In conclusion, infections caused by P. jirovecii mutants potentially resistant to sulfonamides are still rare events in Bulgaria. DHPS genotype 1 at codons 55 and 57 is the predominant P. jirovecii strain in the country.

Risk Factors and Prognostic Scoring Model for 28-Day Mortality in Hematologic Patients with Stenotrophomonas Maltophilia Bacteremia

Objective: Patients with hematologic diseases are at a higher risk for Stenotrophomonasmaltophilia(SM) bacteremia, which poses significant burden on morbidity and mortality. The aim of this study was to evaluate the early predictors of 28-day mortality in hematologic patients with SM bacteremia and to construct a reliable prediction model which can be used to identify patients at higher risk for mortality. Methods: This retrospective analysis of 131 hospitalized patients diagnosed with SM bacteremia was conducted in a tertiary blood disease center in Tianjin, China, from January 2012 to June 2023. Univariate analysis and multivariate logistic regression analysis were used to identify prognostic risk factors and develop a prognostic mortality scoring system and internally validated by bootstrap method (resampling = 1000). Results: The overall 28-day mortality rate in our study was 29.77% (39/131). The mean age was 45 (IQR 30.5-56.0) years and 70 individuals (53.44%) were diagnosed with myeloid malignancies. The existing condition severity-related scores did not perform well in predicting 28-day mortality for the patients in our population (AUROC values: SOFA: 0.842; ECOG: 0.831; APACHE Ⅱ: 0.709; SAPS Ⅱ: 0.675; aCCI: 0.654; Pitt score: 0.629). Through univariate and multivariate analysis, we identified four independent risk factors associated with 28-day mortality: SOFA score (OR = 3.67, 95% CI 1.99-6.78, P < 0.001; score = corresponding SOFA score), age ≥ 60 years (OR = 6.95, 95% CI 1.44-33.55, P = 0.0158; score = 2), bloody sputum or hemoptysis (OR = 5.32, 95% CI 1.08-26.29, P = 0.0402; score = 2) and neutropenia duration ≥ 25 days (OR = 3.92, 95% CI 1.01-15.26, P = 0.0487; score = 1). These factors were used to develop a prognostic scoring model, which yielded good discrimination (AUC = 0.889, 95% CI: 0.829-0.949) and calibration (Hosmer-Lemeshow goodness-of-fit test P = 0.998), with similar performance in the internal bootstrap validation (AUC = 0.888). Furthermore, all patients were divided into the high-risk group (≥ 7 points) and the low-risk group (< 7 points) based on the model and compared using Kaplan-Meier curves and log-rank tests. Additionally, we founded that the use of trimethoprim-sulfamethoxazole (TMP/SMX) after infection was associated with a better prognosis ( P = 0.012). Conclusions: The prediction model, utilizing SOFA score, age, bloody sputum or hemoptysis and neutropenia duration, proves to be an effective tool for early identification of hematologic patients with SM bacteremia at high risk of mortality.

2738. Two-step sulfonamide antibiotic challenges in patients who require treatment with trimethoprim-sulfamethoxazole at an academic medical center: Outcomes in a largely immunocompromised population

Abstract Background Sulfonamide antibiotic allergy is the second most reported medication allergy. The allergy label limits the use of trimethoprim-sulfamethoxazole (TMP-SMX), the antibiotic of choice for pneumocystis jirovecii pneumonia (PJP), Toxoplasma, and many types of urinary tract infections. Immunocompromised patients, including solid organ transplant recipients, are considered to be at a higher risk for developing an infection. While penicillin allergies are commonly tested and patients delabeled, sulfonamide challenges are not as prevalent. Patients who are tested following a transplant may be on medications that lower the negative predictive value of the challenge, raising questions about whether they truly passed the challenge or whether mild reactions were masked. Methods: Thirty-seven patients labeled with a sulfonamide allergy who were evaluated and challenged with two doses of TMP-SMX were included. Adults (≥18 years) with a sulfonamide antibiotic allergy were evaluated and challenged between June 2020 and May 2023. Data collection included the number of patients challenged and delabeled, number of patients who had reactions and what type of reaction, and proportion of patients who completed the treatment or prophylaxis course for which TMP-SMX was the first-line antibiotic. Results Thirty-seven patients were challenged, of which twenty-seven patients were immunocompromised (73%). Thirty-four (92%) passed the sulfonamide challenge and were delabeled, and thirty-two (86%) completed the full course of TMP-SMX prophylaxis or treatment. Nineteen patients (51%) were tested following immunosuppression or antihistamine treatment due to a new transplant. Five patients were not able to be delabeled due to mild or delayed reactions to the challenge or treatment, including two patients that passed the sulfonamide challenge and were delabeled but had a mild reaction during SMX-TMP therapy and were relabeled. Conclusion The benefits of sulfonamide antibiotic allergy testing can have great effects in immunocompromised patients in preventing the use of second-line antibiotics. Sulfonamide challenges were shown to be safe and effective in immunocompromised patients in delabeling the sulfonamide antibiotic allergy and leading to the completion of treatment with TMP-SMX. Disclosures Shyam Joshi, MD, Cogent: Honoraria|Leo Pharma: Honoraria|Nectar Allergy: Advisor/Consultant|Nectar Allergy: Stocks/Bonds|Sanofi/Regeneron: Advisor/Consultant|Sanofi/Regeneron: Honoraria|Takeda: Honoraria

Prevalence of Trimethoprim-Sulfamethoxazole Adverse Reaction Mislabelling in Australia

Introduction: Trimethoprim-sulfamethoxazole (TMP-SMX) is an important antibiotic, with the most compelling indications for Pneumocystis jirovecii pneumonia prophylaxis and methicillin-resistant Staphylococcus aureus treatment. Previous adverse reactions (AR) to TMP-SMX may limit the usability of TMP-SMX. Electronic medical record (EMR) of AR for other antibiotics has previously been shown to be inaccurate; however, the extent to which this occurs for TMP-SMX is unknown. Methods: A multi-centre retrospective observational study was conducted for consecutive inpatient admissions over a 2.5-year period commencing 2020. Adverse reactions to TMP-SMX recorded in the EMR were collected and reviewed by two independent medical officers using pre-defined expert criteria for the classification of allergies and intolerances. Results: TMP-SMX AR were present in the EMR of 759 individuals (prevalence 0.6%). The majority were labelled as allergy (725, 95.5%) rather than intolerance (34, 4.5%). Most common AR were rash, vomiting, and swelling. When classified against the gold-standard expert criteria, there were 437 allergies (57.6%) and 159 intolerances (21.0%). Overall, the number of incorrect EMR AR labels was 133/759 (17.5%). Both medical and surgical specialties had significant numbers of patients with TMP-SMX AR labels and incorrectly classified EMR AR labels. Conclusion: TMP-SMX AR labels affect inpatients admitted under multiple specialty units. The user-entered categorization as allergy or intolerance labels in EMRs are frequently used incorrectly. These incorrect labels may inappropriately contraindicate the use of TMP-SMX, and formal evaluation of TMP-SMX ARs with immunological assessment and relabelling where appropriate may increase the use of this agent.

A systematic review of the clinical impact of small colony variants in patients with cystic fibrosis

BackgroundCystic fibrosis (CF) is a life-limiting disorder that is characterised by respiratory tract inflammation that is mediated by a range of microbial pathogens. Small colony variants (SCVs) of common respiratory pathogens are being increasingly recognised in CF. The aim of this systematic review is to investigate the prevalence of SCVs, clinical characteristics and health outcomes for patients with CF, and laboratory diagnostic features of SCVs compared to non-small colony variants (NCVs) for a range of Gram-positive and Gram-negative respiratory pathogens.MethodsA literature search was conducted (PubMed, Web of Science, Embase and Scopus) in April 2020 to identify articles of interest. Data pertaining to demographic characteristics of participants, diagnostic criteria of SCVs, SCV prevalence and impact on lung function were extracted from included studies for analysis.ResultsTwenty-five of 673 studies were included in the systematic review. Individuals infected with SCVs of Staphylococcus aureus (S. aureus) were more likely to have had prior use of the broad-spectrum antibiotic trimethoprim sulfamethoxazole (p < 0.001), and the prevalence of SCVs in patients infected with S. aureus was estimated to be 19.3% (95% CI: 13.5% to 25.9%). Additionally, patients infected with SCVs of Gram-negative and Gram-positive pathogens were identified to have a lower forced expiratory volume in one second percentage predicted (-16.8, 95% CI: -23.2 to -10.4) than those infected by NCVs. Gram-positive SCVs were commonly described as small and non-haemolytic, grown on Mannitol salt or blood agar for 24 h at 35°C and confirmed using tube coagulase testing.ConclusionThe findings of this systematic review demonstrate that SCVs of S. aureus have a high prevalence in the CF community, and that the occurrence of SCVs in Gram-positive and Gram-negative pathogens is linked to poorer respiratory function. Further investigation is necessary to determine the effect of infection by SCVs on the CF population.

Trimethoprim-sulfamethoxazole prophylaxis during treatment of granulomatosis with polyangiitis with rituximab in the United States of America: a retrospective cohort study

BackgroundAntibiotic prophylaxis is recommended during ANCA-associated vasculitis (AAV) induction. We aimed to describe the frequency, persistence, and factors associated with trimethoprim-sulfamethoxazole (TMP-SMX) use in an adult population sample with granulomatosis with polyangiitis (GPA) treated with rituximab (RTX).MethodsWe identified adults with GPA treated with RTX within the Merative™ Marketscan® Research Databases (2011–2020). TMP-SMX prophylaxis was defined as a ge 28-day prescription dispensed within a month of starting RTX. We estimated TMP-SMX persistence, allowing prescription refill gaps of 30 days. Multivariable logistic regression and Cox proportional hazards regression assessed the factors associated with baseline TMP-SMX use and persistence, respectively. Covariates included age, sex, calendar year, insurance type, immunosuppressant use, hospitalization, and co-morbidities.ResultsAmong 1877 RTX-treated GPA patients, the mean age was 50.9, and 54% were female. A minority (n = 426, 23%) received TMP-SMX with a median persistence of 141 (IQR 83–248) days. In multivariable analyses, prophylaxis was associated with prednisone use in the month prior to RTX (ge 20 mg/day vs none, OR 3.96; 95% CI 3.0–5.2; 1–19 mg/day vs none, OR 2.63; 95% CI 1.8–3.8), and methotrexate use (OR 1.48, 95% CI 1.04–2.1), intensive care (OR 1.95; 95% CI 1.4–2.7), and non-intensive care hospitalization (OR 1.56; 95% CI 1.2–2.1) in the 6 months prior to RTX. Female sex (OR 0.63; 95% CI 0.5–0.8) was negatively associated with TMP-SMX use.ConclusionsTMP-SMX was dispensed to a minority of RTX-treated GPA patients, more often to those on glucocorticoids and with recent hospitalization. Further research is needed to determine the optimal use and duration of TMP-SMX prophylaxis following RTX in AAV.

Gut Microbiota-Mediated Pharmacokinetic Drug-Drug Interactions between Mycophenolic Acid and Trimethoprim-Sulfamethoxazole in Humans.

Mycophenolic acid (MPA) and trimethoprim-sulfamethoxazole (TMP-SMX) are commonly prescribed together in certain groups of patients, including solid organ transplant recipients. However, little is known about the pharmacokinetic drug-drug interactions (DDIs) between these two medications. Therefore, the present study aimed to determine the effects of TMP-SMX on MPA pharmacokinetics in humans and to find out the relationship between MPA pharmacokinetics and gut microbiota alteration. This study enrolled 16 healthy volunteers to take a single oral dose of 1000 mg mycophenolate mofetil (MMF), a prodrug of MPA, administered without and with concurrent use of TMP-SMX (320/1600 mg/day) for five days. The pharmacokinetic parameters of MPA and its glucuronide (MPAG) were measured using high-performance liquid chromatography. The composition of gut microbiota in stool samples was profiled using a 16S rRNA metagenomic sequencing technique during pre- and post-TMP-SMX treatment. Relative abundance, bacterial co-occurrence networks, and correlations between bacterial abundance and pharmacokinetic parameters were investigated. The results showed a significant decrease in systemic MPA exposure when TMP-SMX was coadministered with MMF. Analysis of the gut microbiome revealed altered relative abundance of two enriched genera, namely the genus Bacteroides and Faecalibacterium, following TMP-SMX treatment. The relative abundance of the genera Bacteroides, [Eubacterium] coprostanoligenes group, [Eubacterium] eligens group, and Ruminococcus appeared to be significantly correlated with systemic MPA exposure. Coadministration of TMP-SMX with MMF resulted in a reduction in systemic MPA exposure. The pharmacokinetic DDIs between these two drugs were attributed to the effect of TMP-SMX, a broad-spectrum antibiotic, on gut microbiota-mediated MPA metabolism.

Trimethoprim-sulfamethoxazole prevents interstitial pneumonitis in B-cell lymphoma patients receiving chemotherapy: a propensity score matching analysis.

B-cell lymphoma is the most prevalent type of non-Hodgkin lymphoma, for which the standard treatment regimen includes rituximab combined with CHOP. However, some patients may develop interstitial pneumonitis (IP), which can be caused by various factors; one of the most important factors is Pneumocystis jirovecii. It is crucial to investigate the pathophysiology of IP and implement preventive measures since IP can be fatal for some people. The data were collected from the First Affiliated Hospital, Zhejiang University School of Medicine, where patients with B-cell lymphoma received the R-CHOP/R-CDOP regimen with or without prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX). Multivariable logistic regression and propensity score matching (PSM) were used to investigate any potential association. Eight hundred thirty-one patients with B-cell lymphoma were classified into two groups: the non-prophylaxis group without TMP-SMX (n=699) and the prophylaxis group with TMP-SMX (n = 132). IP occurred in 66 patients (9.4%, all in the non-prophylaxis group), with an onset median of three cycles of chemotherapy. Multiple logistic regression analysis demonstrated that IP incidence was associated with pegylated liposome doxorubicin (OR=3.29, 95% CI 1.84-5.90, P<0.001). After utilizing a 1:1 matching algorithm for PSM, 90 patients from each group were obtained. There was a statistical difference between the two cohorts in the IP incidence (non-prophylaxis 12.2% vs prophylaxis 0.0%, P <0.001). The prophylactic use of TMP-SMX could prevent the occurrence of IP whose risk factor was pegylated liposome doxorubicin after chemotherapy for B-cell lymphoma.

Evaluation of Adverse Drug Reaction Caused by Concomitant Use of Trimethoprim-Sulfamethoxazole and Methotrexate in Pediatric Acute Lymphoblastic Leukemia Patients

Evaluation of Adverse Drug Reaction Caused by Concomitant Use of Trimethoprim-Sulfamethoxazole and Methotrexate in Pediatric Acute Lymphoblastic Leukemia Patients

Prophylactic Trimethoprim-Sulfamethoxazole for Allogeneic Hematopoietic Stem Cell Transplant Recipients During the Pre-engraftment Period

BackgroundOur institution has used trimethoprim-sulfamethoxazole (TMP-SMX) as the antibacterial agent of choice for infection prophylaxis during the pre-engraftment period in the allogeneic transplant (allo-HCT) population.MethodsThis retrospective, single center study was developed to compare the safety of that antibacterial prophylaxis to fluoroquinolones in allo-HCT. The primary endpoint was time to neutrophil engraftment.ResultsA total of 366 patients were reviewed (TMP-SMX n = 332, fluoroquinolone n = 34). No difference in days to neutrophil engraftment was found (median 15 versus 16 days, p = 0.62). Hyperkalemia was more common in the TMP-SMX cohort (32.2% versus 14.7%, p = 0.035); this did not contribute to a higher rate of agent discontinuation or arrhythmia. There was no significant difference in the incidence of neutropenic fever; however, those in the TMP-SMX cohort were more likely to have microbiologically confirmed bacteremia (24.1% versus 8.8% respectively, p = 0.043). There was no significant difference in infections. No long-term implication of prophylactic antibacterial agent selection was observed in terms of graft-versus-host-disease, underlying disease relapse, or mortality.ConclusionThe use of TMP-SMX was associated with a higher likelihood of bacteremia and hyperkalemia; however, this did not result in increased hospital stay, escalation of care, or mortality. The use of TMP-SMX for prophylaxis during the pre-engraftment period for allo-HCT recipients is safe and effective.

1183. Serotype Prevalence and Antimicrobial Resistance Patterns of Streptococcus pneumoniae in Ecuador

Abstract Background Streptococcus pneumoniae is a leading cause of pneumonia and meningitis in the world, and it is under-researched in Ecuador. Reported mortality in this country was 280 cases per year. The national policy of the country established the obligatory application of the pneumococcal vaccine to infants in 2010, but there is no such law for adults. The serotypes' distribution and resistance patterns are unknown. This study aims to describe the serotypes and resistance patterns of Strepcococcus pneumoniae isolations in Ecuador. Methods A retrospective study of all positive cultures for Streptococcus pneumoniae (blood, other sterile liquids, respiratory, ocular, and ear samples) was conducted in three hospitals and one reference laboratory in Ecuador. Serotype data, E-test results for penicillin and ceftriaxone, resistance patterns and susceptibility to other antibiotics by the Kirby-Bauer test were collected. Results A total of 214 samples were evaluated: 18.8% (39) were tracheal secretions, 36.7% (76) sputum, 5.7% (11) cerebrospinal fluid, 17.4% (36) blood, 2.9% (6) pleural fluid, and 27.9% (37) others: ocular, abdominal, and ear secretions. A wide distribution of serotypes was observed. The most prevalent were 19A, 14 and 3. Figure 1 shows penicillin resistance increased per year. However, 93,3% (166) of the strains were ceftriaxone susceptible and 100% of the isolates tested showed susceptibility to vancomycin. Susceptibility to levofloxacin was 99.2%; only one isolate was resistant. No microorganism tested for linezolide was resistant. For other antibiotics, a high level of resistance was identified; 69.3% (54) for trimethoprim sulfamethoxazole, 47.5% (107) for erythromycin and 37.6% (104) for clindamycin. Figure 1.S. pneumoniae penicillin susceptibility percet by year in Ecuador Conclusion It is important to know the resistance patterns and serotypes of S. pneumoniae for therapeutic and epidemiologic decisions. In countries with more than 12% ceftriaxone resistance to Streptococcus pneumoniae, it is suggested for use as an empiric vancomicyn. Nowadays, in Ecuador, the resistance patterns don’t apply to extended vancomycin use. We do not recommend the empirical use of trimethoprim sulfamethoxazole, macrolides and clindamycin for S. pneumoniae infections. Disclosures All Authors: No reported disclosures.

Voriconazole therapeutic drug monitoring and hepatotoxicity in critically ill patients: A nationwide multi-centre retrospective study

To characterize trough concentrations (Cmin) of voriconazole and associated hepatotoxicity, and to determine predictors of hepatotoxicity and identify high-risk groups in critically ill patients. This was a nationwide, multi-centre, retrospective study. Cmin and hepatotoxicity were studied from 2015 to 2020 in 363 critically ill patients who received voriconazole treatment. Logistic regression and classification and regression tree (CART) models were used to identify high-risk patients. Large interindividual variability was observed in initial voriconazole Cmin and concentrations ranged from 0.1 mg/L to 18.72 mg/L. Voriconazole-related grade ≥2 hepatotoxicity developed in 101 patients, including 48 patients with grade ≥3 hepatotoxicity. The median time to hepatotoxicity was 3 days (range 1-24 days), and 83.2% of cases of hepatotoxicity occurred within 7 days of voriconazole initiation. Voriconazole Cmin was significantly associated with hepatotoxicity. The CART model showed that significant predictors of grade ≥2 hepatotoxicity were Cmin >3.42 mg/L, concomitant use of trimethoprim-sulfamethoxazole or tigecycline, and septic shock. The model predicted that the incidence of grade ≥2 hepatotoxicity among these high-risk patients was 48.3-63.4%. Significant predictors of grade ≥3 hepatotoxicity were Cmin >6.87 mg/L, concomitant use of at least three hepatotoxic drugs, and septic shock; the predictive incidence among these high-risk patients was 22.7-36.8%. Higher voriconazole Cmin, septic shock and concomitant use of hepatotoxic drugs were the strongest predictors of hepatotoxicity. Plasma concentrations of voriconazole should be monitored early (as soon as steady state is achieved) to avoid hepatotoxicity.

SEVERE INFLAMMATORY RESPONSE SYNDROME AFTER TMP-SMX IN A HEALTHY PATIENT

<h3>Introduction</h3> We report a case of systemic inflammatory response syndrome (SIRS) caused by trimethoprim-sulfamethoxazole (TMP-SMX). To our knowledge, this is the first report of TMP-SX-associated SIRS in a healthy individual. <h3>Case Description</h3> A 36 year-old, healthy, Irish-American male without prior medication allergy was transferred to our tertiary referral center in three-pressor shock, six days after initiating TMP-SMX DS BID for pilonidal cyst treatment. He previously tolerated TMP-SX in his 20s. Prior to arrival he received empiric broad-spectrum antibiotics and a single dose of systemic corticosteroids. In our ICU, he was febrile, tachycardic and hypotensive. His exam was notable for violaceous papules on extremities and trunk. Labs notable for acuterenal injury, lactic acidosis, leukocytosis to 39.92, cardiomyopathy with EF 25%, and bibasilar infiltrates. Broad immunologic, rheumatologic and infectious evaluations were negative, including HIV. Skin biopsy demonstrated a leukocytoclastic vasculitis. Antibiotics were stopped; additional steroids were not administered. He improved with supportive care and was discharged to home within 2 weeks. <h3>Discussion</h3> Prior cases of TMP-SMX causing serious adverse drug reactions with SIRS have been reported in HIV-infected persons. There is a single report of a severe systemic reaction to TMP-SMX in an HIV-negative individual but who hadCD4+ lymphocytopenia . In a patient with a recent history of TMP-SMX use, presenting with shock and/or SIRS, drug allergy should be considered in the differential diagnosis. CD4+ level could be checked to further characterize this rare reaction.

Risk Factors for Trimethoprim and Sulfamethoxazole-Resistant Escherichia Coli in ED Patients with Urinary Tract Infections

BackgroundWhile trimethoprim-sulfamethoxazole (TMP-SMX) is recommended as one of the first-line empiric therapies for treatment of acute uncomplicated cystitis, institutions that observe resistance rates exceeding 20% for Escherichia coli (E. coli) should utilize alternative empiric antibiotic therapy per the Infectious Diseases Society of America (IDSA). Identifying risk factors associated with TMP-SMX resistance in E. coli may help guide empiric antibiotic prescribing for urinary tract infections (UTIs). MethodsThis multicenter, retrospective study included adult patients who were discharged from 12 emergency departments (EDs) with a urine culture positive for E. coli between January 1, 2019 and December 31, 2019. Logistic regression was used to assess the relationship between potential risk factors and TMP-SMX resistance. The overall institutional antimicrobial resistance rates for E. coli were compared to the rates seen in the study population of ED urinary isolates. ResultsAmong 427 patients included from a randomized sample of 500 with a urine culture positive for E. coli, 107 (25.1%) were resistant to TMP-SMX. Three predictors of TMP-SMX resistance were identified: recurrent UTI (OR 2.27 [95% CI 1.27–3.99]), genitourinary abnormalities (OR 2.31 [95% CI 1.17–4.49]), and TMP-SMX use within 90 days (OR 8.77 [95% CI 3.19–28.12]). When the antibiotic susceptibilities for this ED cohort were compared to the institutional antibiogram, the TMP-SMX resistance rate was found to be higher in the ED population (25.1% vs 20%). ConclusionsTMP-SMX should likely be avoided as first-line therapy for UTI in patients who have recurrent UTIs, genitourinary abnormalities, or have previously received TMP-SMX within the past 90 days. The use of an ED-specific antibiogram should be considered for assessing local resistance rates in this population.

Severe hyponatremia due to trimethoprim-sulfamethoxazole-induced SIADH

Hyponatremia, a serum sodium level of <135 mEq/L, is the most common electrolyte abnormality occurring in 5%–35% of hospitalized patients. It is a predictor of increased morbidity and mortality. Diuretics, psychotropic, and antiepileptic drugs are commonly implicated in drug-induced hyponatremia. Trimethoprim-sulfamethoxazole and spironolactone are two commonly prescribed drugs; unfortunately, most providers are unfamiliar with these two drugs causing hyponatremia. Simultaneous use of trimethoprim-sulfamethoxazole and spironolactone can cause serious drug interactions that increase the risk of hyponatremia, hyperkalemia, and overall mortality. Despite recommendations to avoid using these two drugs concurrently, many healthcare providers continue to prescribe them together. We report a case of an elderly female with severe hyponatremia caused by trimethoprim-sulfamethoxazole superimposed on a chronic but stable mild hyponatremia.

A single- or two-step challenge versus a six-step challenge in non–HIV-infected patients with a sulfonamide antibiotic allergy label: A retrospective case series

Antibiotics account for the majority of drug allergy label reports,1 and sulfonamide antibiotics are the second most commonly reported class of outpatient antibiotic allergy labels.2 Sulfonamide antibiotics can cause a variety of hypersensitivity reactions (HSRs) ranging from rare immediate-onset IgE-mediated allergic reactions and much more common delayed-onset benign T-cell–mediated rashes to extremely rare severe cutaneous adverse reactions (SCARs).3 As a consequence, a sulfonamide antibiotic allergy label limits the use of trimethoprim-sulfamethoxazole (TMP-SMX), the first option for Pneumocystis jirovecii pneumonia prophylaxis, and a preferred agent for the treatment of methicillin-resistant Staphylococcus aureus.

1126. Short-Course Therapy and Transition to Enteral Antibiotics for Uncomplicated Bacteremia Due to Enterobacterales Species

Abstract Background Gram-negative bacteremia historically has been treated with 10-14 days of parenteral antibiotics. However, data supporting this practice are lacking, and recent evidence shows equivalent outcomes for short-course (SC) therapy (7 days) and early (by day 5) conversion to highly bioavailable enteral (PO) antibiotics for Enterobacterales bacteremia. Methods Under a QI framework, we used PDSA cycles to reduce treatment duration and increase use of PO levofloxacin or trimethoprim-sulfamethoxazole for uncomplicated Enterobacterales bacteremia among Infectious Diseases (ID) clinicians at a children’s hospital in Boston, MA. We conducted an education session on evidence to support these practices for ID faculty and fellows in October 2020. In December 2020, we implemented standardized recommendations for a 7-day duration and early PO transition for eligible patients (≥ 3-months-old, ≤ 2 days monomicrobial bacteremia, with source control and return to baseline clinical status) that could be inserted automatically into electronic consult notes. In February 2021, we reinforced this practice to ID providers. We collected data before and after these interventions on ID recommendations and on patients’ actual antibiotic management. Results From 11/01/20 to 05/31/21, mean recommended treatment decreased from 10.6 to 9.5 days; however, mean duration received was similar (11.2 vs 11.7 days) (Figure 1). The percentage of patients for whom ID recommended PO conversion and in whom transition to PO agents by day 5 occurred increased from 27% to 37.5%. Figure 1. Change in average duration of antibiotics recommended and received, in days Conclusion Education and creation of automated standardized recommendations led to decreased recommended treatment durations and increased PO conversions for Enterobacterales bacteremia, but only modestly. This quality improvement initiative demonstrates the potential benefits of education and electronic documentation tools to facilitate evidence-based practice changes, but also highlights the difficulty in changing practice even amongst ID clinicians. Further PDSA cycles will be targeted at increasing more consistent awareness among a large ID division in addition to other stakeholders. Disclosures Gabriella S. Lamb, MD, MPH, Nothing to disclose

Efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of pneumocystis pneumonia in human immunodeficiency virus-negative immunodeficient patients: A systematic review and meta-analysis.

BackgroundPneumocystis pneumonia (PCP) has a significant impact on the mortality of immunocompromised patients. It is not known whether the prophylactic application of trimethoprim-sulfamethoxazole (TMP-SMZ) can reduce the incidence of PCP and mortality in the human immunodeficiency virus (HIV)-negative immunodeficient population. The safety profile is also unknown. There have been few reports on this topic. The aim of this study was to systematically evaluate the efficacy and safety of the use of TMP-SMZ for the prevention of PCP in this population of patients from the perspective of evidence-based medicine.MethodsA comprehensive search without restrictions on publication status or other parameters was conducted. Clinical randomized controlled trials (RCTs) or case-control trials (CCSs) of TMP-SMZ used for the prevention of PCP in HIV-negative immunocompromised populations were considered eligible. A meta-analysis was performed using the Mantel-Haenszel fixed-effects model or Mantel-Haenszel random-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and reported.ResultsOf the 2392 records identified, 19 studies (n = 4135 patients) were included. The efficacy analysis results indicated that the PCP incidence was lower in the TMP-SMZ group than in the control group (OR = 0.27, 95% CI (0.10, 0.77), p = 0.01); however, the rate of drug discontinuation was higher in the TMP-SMZ group than in the control group (OR = 14.31, 95% CI (4.78, 42.91), p<0.00001). In addition, there was no statistically significant difference in the rate of mortality between the two groups (OR = 0.54, 95% CI (0.21, 1.37), p = 0.19). The safety analysis results showed that the rate of adverse events (AEs) was higher in the TMP-SMZ group than in the control group (OR = 1.92, 95% CI (1.06, 3.47), p = 0.03).ConclusionsTMP-SMZ has a better effect than other drugs or the placebo with regard to preventing PCP in HIV-negative immunocompromised individuals, but it may not necessarily reduce the rate of mortality, the rate of drug discontinuation or AEs. Due to the limitations of the research methodologies used, additional large-scale clinical trials and well-designed research studies are needed to identify more effective therapies for the prevention of PCP.

Trimethoprim-sulfamethoxazole use is associated with improved lung function in pediatric asthma

Trimethoprim-sulfamethoxazole use is associated with improved lung function in pediatric asthma

Dihydropteroate Synthase (DHPS) Gene Mutations and Mitochondrial Large Subunit (mtLSU) rRNA Genotype Variations in Pneumocystis jirovecii Strains

Pneumocystis jirovecii is an atypical fungus that causes Pneumocystis pneumonia (PCP) in HIV/AIDS and immunocompromised patients. Antibiotics containing sulfa and sulfone groups are widely used in PCP prophylaxis and treatment. Especially, long-term use of trimethoprim sulfamethoxazole (TMP-SMX) is known to cause certain point mutations associated with drug resistance in the P.jirovecii dihydropteroate synthase (DHPS) gene. In addition, DHPS and mitochondrial large subunit (mtLSU) rRNA genotype characterization provides important data on the epidemiology of P.jirovecii. In this study, it was aimed to investigate the DHPS and mtLSU rRNA gene polymorphisms of P.jirovecii strains isolated from immunocompromised patients in Mersin University Hospital. In this study, 16 P.jirovecii positive samples, which isolated from 96 patients samples, between August 2016 and February 2018, were included. P.jirovecii mtLSU rRNA genotypes were determined by sequence analysis according to polymorphisms at the 85th and 248th nucleotide positions. Nested PCR and RFLP method was applied for mutation analysis of DHPS locus, 165th and 171st nucleotide positions. In the DHPS mutation analysis, 12/16 (75%) wild type (W165/W171) and 4/16 (25%) mutant type (M165/W171) were detected. Two mutant types belonged to HIV/AIDS positive patients with PCP and had a history of prophylaxis; the other 2 mutant types belonged to patients with colonization. In the study, a history of prophylaxis in 3 (19%) of the 16 patients were recorded, and mutant type was detected in these 2 of 3 patients. According to mtLSU-rRNA analysis, 3 different genotypes were obtained from 16 P.jirovecii isolates. In our region, genotype 2 (43.75%; n= 7) was the most common genotype, genotype 1 (37.5%; n= 6) was the second common and genotype 3 (18.75%; n= 3) was the least one. Genotype 4 was not detected in our region. When DHPS and mtLSU-rRNA were evaluated as multilocus, five different genotypes were observed. As a result, these findings provided important data on P.jirovecii epidemiology in our region and potential drug-resistant strains showed a risk of transmission in immunosuppressive patients. Multicenter studies involving more P.jirovecii isolates are needed to better define the epidemiology of P.jirovecii in our region and in our country.