Trimethoprim

Trimethoprim is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections.

Evaluation of trimethoprim-sulfamethoxazole based combination therapy against Stenotrophomonas maltophilia: in vitro effects and clinical efficacy in cancer patients.[Pubmed:28257816]

Int J Infect Dis. 2017 May;58:18-21.

OBJECTIVES: The aim of this study was to evaluate the in vitro effects and clinical efficacies of Trimethoprim-sulfamethoxazole (SXT) combined with other antimicrobial agents against Stenotrophomonas maltophilia. METHODS: In vitro analysis was conducted on 89 S. maltophilia strains isolated from blood and the respiratory tract between June 2012 and October 2014. Levofloxacin (LVX), ticarcillin-clavulanic acid (TIM), and minocycline (MIN) were selected for an examination of their effects when individually combined with SXT by the checkerboard method. In addition, 29 S. maltophilia bacteremia cases were reviewed and the clinical efficacies of SXT-based combination therapies were analyzed. RESULTS: SXT+LVX showed synergy in 21, no interactions in 61, and antagonism in 7. SXT+TIM showed synergy in 71, and no interactions in 18. SXT+MIN showed synergy in 10, and no interactions in 79. The review of clinical data indicated that a combination of SXT+fluoroquinolone was not associated with improved prognosis compared with monotherapy. CONCLUSIONS: The in vitro data indicated that SXT+TIM had beneficial microbiological effects and was not antagonistic. Our in vitro and clinical data analyses do not support the routine use of SXT+fluoroquinolone combination therapy for S. maltophilia infection.

Integron-Associated DfrB4, a Previously Uncharacterized Member of the Trimethoprim-Resistant Dihydrofolate Reductase B Family, Is a Clinically Identified Emergent Source of Antibiotic Resistance.[Pubmed:28242670]

Antimicrob Agents Chemother. 2017 Apr 24;61(5). pii: AAC.02665-16.

Whole-genome sequencing of Trimethoprim-resistant Escherichia coli clinical isolates identified a member of the Trimethoprim-resistant type II dihydrofolate reductase gene family (dfrB). The dfrB4 gene was located within a class I integron flanked by multiple resistance genes. This arrangement was previously reported in a 130.6-kb multiresistance plasmid. The DfrB4 protein conferred a >2,000-fold increased Trimethoprim resistance on overexpression in E. coli Our results are consistent with the finding that dfrB4 contributes to clinical Trimethoprim resistance.

Recurrent trimethoprim-sulfamethoxazole-induced aseptic meningitis with associated ampicillin-induced myoclonic twitches.[Pubmed:28291512]

Int J Clin Pharmacol Ther. 2017 Jul;55(7):627-629.

OBJECTIVE: To report a case of recurrent Trimethoprim-sulfamethoxazole-induced aseptic meningitis with associated ampicillin-induced myoclonic twitches. MATERIALS AND METHODS: The patient was investigated using cerebral computed tomography, magnetic resonance imaging, cerebrospinal fluid examination, and electroencephalography. Written informed consent was obtained from the patient for access to clinical files for research purposes and publication. RESULTS: We present a middle-aged woman with two recurrent episodes of aseptic meningitis after treatment with Trimethoprim-sulfamethoxazole. Additionally, she developed myoclonic twitches as a rare side effect of ampicillin. CONCLUSION: Aseptic meningitis is a rare adverse reaction to medications like antibiotics. The pathogenesis of Trimethoprim-sulfamethoxazole-induced aseptic meningitis is not yet completely understood, but an immune-mediated hypersensitivity reaction is suspected. If patients with an antibiotic therapy due to a systemic or local infection present with severe headache, not only common diagnosis of a parainfectious headache, but also antibiotic-induced aseptic meningitis should be considered..

Efficacy and Safety of Dapsone Versus Trimethoprim/Sulfamethoxazol for Pneumocystis Jiroveci Prophylaxis in Children With Acute Lymphoblastic Leukemia With a Background of Ethnic Neutropenia.[Pubmed:28234744]

J Pediatr Hematol Oncol. 2017 Apr;39(3):203-208.

STUDY OBJECTIVE: To study dapsone in comparison with Trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis jiroveci (PJP) prophylaxis in children with acute lymphoblastic leukemia (ALL). DESIGN: A retrospective study with a prospective follow-up. PATIENTS: Pediatric ALL patients diagnosed between May 2009 and May 2014, who are still receiving or have completed their maintenance chemotherapy. Patients who completed chemotherapy were prospectively followed up for neutropenia. METHODS: TMP/SMX was used as the initial PJP prophylaxis. An alternative drug was indicated if the patient remained cytopenic for >3 weeks. Average absolute neutrophilic count (ANC), average % of oral mercaptopurine (6-MP), and methotrexate doses were calculated over a period of 6 months before and after shifting to dapsone. RESULTS: Sixty-two ALL patients were eligible for analysis. Twenty-four patients (38.7%) received TMP/SMX for PJP prophylaxis, whereas 34 patients received Dapsone (54.8%). Only 3 patients received IV pentamidine (4.8%), whereas 1 patient (1.6%) received atovaquone. The incidence of prophylaxis failure was 1/1041 months on TMP/SMX and 1/528 months on dapsone. After shifting to dapsone, patients maintained significantly higher ANC (1.46+/-0.46 vs. 1.17+/-0.40, P=0.0053), and received significantly higher doses of 6-MP (62.61%+/-11.45 vs. 57.45+/-10.14, P=0.0081) and methotrexate (64.9%+/-14.29 vs. 56.5%+/-9.9, P=0.0176), with a significantly shorter duration of chemotherapy interruption (1.94+/-1.2 vs. 3.25+/-1.29 wk, P=0.0002). CONCLUSIONS: Dapsone for PJP prophylaxis in ALL allowed patients to maintain higher ANC and to receive higher doses of chemotherapy, while maintaining a low incidence of PJP breakthrough infection.