Trimethoprim-Sulfamethoxazole (Bactrim) Dose Optimization in Pneumocystis jirovecii Pneumonia (PCP) Management: A Systematic Review

Haseeb, Abdul; Abourehab, Mohammed A. S.; Almalki, Wesam; Almontashri, Abdulrahman; Bajawi, Sultan; Aljoaid, Anas M; Alsahabi, Bahni; Algethamy, Manal; AlQarni, Abdullmoin; Iqbal, Muhammad Shahid; Mutlaq, Alaa; Alghamdi, Saleh; Elrggal, Mahmoud E.; Saleem, Zikria; Radwan, Rozan Mohammad; Mahrous, Ahmad Jamal; Faidah, Hani

doi:10.3390/ijerph19052833

Cited by 15 publications

(9 citation statements)

References 49 publications

(87 reference statements)

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“…Sulfonamides inhibit dihydrofolic acid biosynthesis in Gram-negative and Gram-positive bacteria ( 39 , 40 ). Sulfamethoxazole belongs to sulfonamide and is commonly used for routine treatment and prophylaxis against infections with Pneumocystis pneumonia ( 41 , 42 ). Sul1 is assigned to resistant sulfonamides and is widely prevalent in environments including rivers, soils, farms, and even effluents of wastewater treatment plants ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

The microbiome, resistome, and their co-evolution in sewage at a hospital for infectious diseases in Shanghai, China

Ma,

Wu,

Zhang

et al. 2024

Microbiol Spectr

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The emergence of antibiotic-resistant bacteria (ARB) caused by the overuse of antibiotics severely threatens human health. Hospital sewage may be a key transmission hub for ARB. However, the complex link between the microbiome and resistomeresistance in hospital sewage remains unclear. In this study, metagenomic assembly and binning methods were used to investigate the microbial community, resistome, and association of antibiotic resistance genes (ARGs) with ARB in sewage from 10 representative sites (outpatient building, surgery building, internal medicine buildings [IMB1-4], staff dormitory, laboratory animal building, tuberculosis building [TBB], and hospital wastewater treatment plant) of a hospital in Shanghai from June 2021 to February 2022. A total of 252 ARG subtypes, belonging to 17 antibiotic classes, were identified. The relative abundance of KPC-2 was higher at IMBs and TBB than at other sites. Of the ARG-carrying contigs, 47.3%-62.6% were associated with mobile genetic elements, and the proportion of plasmid-associated ARGs was significantly higher than that of chromosome-associated ARGs. Although a similar microbiome composition was shared, certain bacteria were enriched at different sites. Potential pathogens Enterococcus B faecium and Klebsiella pneumoniae were primarily enriched in IMB2 and IMB4, respectively. The same ARGs were identified in diverse bacterial hosts (especially pathogenic bacteria), and accordingly, the latter possessed multiple ARGs. Furthermore, gene flow was frequently observed in the sewage of different buildings. The results provide crucial information on the characterization profiles of resistomes in hospital sewage in Shanghai. IMPORTANCE Environmental antibiotic resistance genes (ARGs) play a critical role in the emergence and spread of antimicrobial resistance, which poses a global health threat. Wastewater from healthcare facilities serves as a significant reservoir for ARGs. Here, we characterized the microbial community along with the resistome (comprising all antibiotic resistance genes) in wastewater from a specialized hospital for infectious diseases in Shanghai. Potential pathogenic bacteria (e.g., Escherichia coli , Pseudomonas aeruginosa , Klebsiella pneumoniae , Enterococcus B faecium ) were frequently detected in hospital wastewater and carried multiple ARGs. A complex link between microbiome and resistome was observed in the wastewater of this hospital. The monitoring of ARGs and antibiotic-resistant bacteria (ARB) in hospital wastewater might be of great significance for preventing the spread of ARB.

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Section: Discussionmentioning

confidence: 99%

The microbiome, resistome, and their co-evolution in sewage at a hospital for infectious diseases in Shanghai, China

Ma,

Wu,

Zhang

et al. 2024

Microbiol Spectr

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“…Co-trimoxazole is an antibiotics indicated for urinary tract infection and Pneumocystis jiroveci pneumonia ( Haseeb et al, 2022 ; Jent et al, 2022 ). The prevalence of skin adverse reaction was 1%–4% among general population treated with co-trimoxazole ( Wolkenstein et al, 1995 ; Masters et al, 2003 ).…”

Section: Hla Susceptibility To Drug-induced Scarmentioning

confidence: 99%

Current understanding of genetic associations with delayed hypersensitivity reactions induced by antibiotics and anti-osteoporotic drugs

Wung¹,

Wang²,

Lai³

et al. 2023

Front. Pharmacol.

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Drug-induced delayed hypersensitivity reactions (DHRs) is still a clinical and healthcare burden in every country. Increasing reports of DHRs have caught our attention to explore the genetic relationship, especially life-threatening severe cutaneous adverse drug reactions (SCARs), including acute generalized exanthematous pustulosis (AGEP), drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). In recent years, many studies have investigated the immune mechanism and genetic markers of DHRs. Besides, several studies have stated the associations between antibiotics-as well as anti-osteoporotic drugs (AOD)-induced SCARs and specific human leukocyte antigens (HLA) alleles. Strong associations between drugs and HLA alleles such as co-trimoxazole-induced DRESS and HLA-B*13:01 (Odds ratio (OR) = 45), dapsone-DRESS and HLA-B*13:01 (OR = 122.1), vancomycin-DRESS and HLA-A*32:01 (OR = 403), clindamycin-DHRs and HLA-B*15:27 (OR = 55.6), and strontium ranelate (SR)-SJS/TEN and HLA-A*33:03 (OR = 25.97) are listed. We summarized the immune mechanism of SCARs, update the latest knowledge of pharmacogenomics of antibiotics- and AOD-induced SCARs, and indicate the potential clinical use of these genetic markers for SCARs prevention in this mini review article.

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“…Second, there were fewer adverse events in the low-dose group than in the conventional-dose group in the present study. TMP-SMX is associated with a dose-dependent incidence of adverse events, such as skin rashes, gastrointestinal disturbances, myelosuppression, renal disturbances, hepatic disturbances, and electrolyte disturbances [32]; 57% of patients with HIV PCP change from this treatment owing to serious adverse events [33].…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 99%

Low-versus conventional-dose trimethoprim-sulfamethoxazole for non-HIV PCP

Nagai

Matsui

Fujioka

et al. 2023

Preprint

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Trimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment for Pneumocystis jirovecii pneumonia (PCP); however, a high incidence of adverse events has been observed. Low-dose TMP-SMX is a potentially effective treatment with fewer adverse events; however, evidence is limited. We aimed to evaluate the efficacy and safety of low-dose TMP-SMX after adjusting for patient background characteristics. In this multicentre retrospective cohort study, we included patients diagnosed with non-human immunodeficiency virus (HIV) PCP and treated with TMP-SMX between June 2006 and March 2021 at three institutions. The patients were classified into low- (TMP equivalent <12.5 mg/kg) and conventional-dose groups (TMP equivalent 12.5-20 mg/kg/day). The primary endpoint was 30-day mortality, and the secondary endpoints were 180-day mortality, adverse events of grade 3 or greater per the Common Terminology Criteria for Adverse Events Version 5.0, and initial treatment completion rates. The background characteristics were adjusted using the overlap weighting method with propensity scores. Fifty-five patients in the low-dose and 81 in the conventional-dose groups were evaluated. There was no significant difference in 30-day mortality (7.6% vs. 14.9%, P = 0.215) or 180-day mortality (18.1% vs. 24.0%, P = 0.416) after adjusting for patient background characteristics. The incidence of adverse events, especially nausea and hyponatremia, was significantly lower in the low-dose group (27.3% vs. 58.6%, P = 0.001). The initial treatment completion rates were 43.8% and 27.7% in the low-dose and conventional-dose groups, respectively. Low-dose TMP-SMX did not alter survival but reduced the incidence of adverse events in patients with non-HIV PCP, compared with conventional-dose TMP-SMX.

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Trimethoprim-Sulfamethoxazole (Bactrim) Dose Optimization in Pneumocystis jirovecii Pneumonia (PCP) Management: A Systematic Review

Cited by 15 publications

References 49 publications

The microbiome, resistome, and their co-evolution in sewage at a hospital for infectious diseases in Shanghai, China

The microbiome, resistome, and their co-evolution in sewage at a hospital for infectious diseases in Shanghai, China

Current understanding of genetic associations with delayed hypersensitivity reactions induced by antibiotics and anti-osteoporotic drugs

Low-versus conventional-dose trimethoprim-sulfamethoxazole for non-HIV PCP

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