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Clinical Journal of the American... Jul 2019Antimicrobial pharmacology and its effect on prescribing is quite complex. Selecting an antibiotic that will optimally treat an infection while minimizing adverse... (Review)
Review
Antimicrobial pharmacology and its effect on prescribing is quite complex. Selecting an antibiotic that will optimally treat an infection while minimizing adverse effects and the development of resistance is only the first step, as one must also consider the patient's individual pharmacokinetic alterations and the pharmacodynamic properties of the drug when prescribing it as well. Patients with CKD may have alterations in their protein binding, volumes of distribution, kidney clearance, and nonrenal clearance that necessitates antibiotic dose adjustments to prevent the development of toxicity. Knowledge of a drug's pharmacodynamics, defined as the relationship between drug exposure and antibacterial efficacy, provides some guidance regarding the optimal way to make dose adjustments. Different pharmacodynamic goals, such as maximizing the time that free (unbound) drug concentrations spend above the minimum inhibitory concentration (MIC) for time dependent drugs (, -lactams) or maximizing the free peak-to-MIC ratio for concentration-dependent antibiotics (, aminoglycosides), require different adjustment strategies; for instance, decreasing the dose while maintaining normal dosing frequency or giving normal (or even larger) doses less frequently, respectively. Patients receiving hemodialysis have other important prescribing considerations as well. The nephrologist or patient may prefer to receive antibiotics that can be administered intravenously toward the end of a dialysis session. Additionally, newer dialysis technologies and filters can increase drug removal more than originally reported. This review will discuss the place in therapy, mechanism of action, pharmacokinetic, pharmacodynamic, and other pharmacologic considerations encountered when prescribing commonly used antibiotics in patients with chronic kidney disease or ESKD.
Topics: Aminoglycosides; Anti-Bacterial Agents; Fluoroquinolones; Humans; Lipopeptides; Methicillin-Resistant Staphylococcus aureus; Renal Insufficiency, Chronic; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 30862698
DOI: 10.2215/CJN.08140718 -
International Journal of Environmental... Feb 2022(1) Background: pneumonia (PCP) has a substantial impact on the morbidity and mortality of patients, especially those with autoimmune disorders, thus requiring optimal... (Review)
Review
(1) Background: pneumonia (PCP) has a substantial impact on the morbidity and mortality of patients, especially those with autoimmune disorders, thus requiring optimal dosing strategies of Trimethoprim-Sulfamethoxazole (TMP-SMX). Therefore, to ensure the safety of TMP-SMX, there is a high demand to review current evidence in PCP patients with a focus on dose optimization strategies; (2) Methods: Various databases were searched from January 2000 to December 2021 for articles in English, focusing on the dose optimization of TMP-SMX. The data were collected in a specific form with predefined inclusion and exclusion criteria. The quality of each article was evaluated using a Newcastle-Ottawa Scale (NOS) for retrospective studies, Joanna Briggs Institute (JBI) critical checklist for case reports, and Cochrane bias tool for randomized clinical trials (RCTs); (3) Results: Thirteen studies met the inclusion criteria for final analysis. Of the 13 selected studies, nine were retrospective cohort studies, two case reports, and two randomized controlled trials (RCT). Most of the studies compared the high-dose with low-dose TMP-SMX therapy for PCP. We have found that a low dose of TMP-SMX provides satisfactory outcomes while reducing the mortality rate and PCP-associated adverse events. This strategy reduces the economic burden of illness and enhances patients' compliance to daily regimen plan; (4) Conclusions: The large-scale RCTs and cohort studies are required to improve dosing strategies to prevent initial occurrence of PCP or to prevent recurrence of PCP in immune compromised patients.
Topics: Cohort Studies; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 35270525
DOI: 10.3390/ijerph19052833 -
JAMA Jul 2021Determination of optimal treatment durations for common infectious diseases is an important strategy to preserve antibiotic effectiveness. (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Determination of optimal treatment durations for common infectious diseases is an important strategy to preserve antibiotic effectiveness.
OBJECTIVE
To determine whether 7 days of treatment is noninferior to 14 days when using ciprofloxacin or trimethoprim/sulfamethoxazole to treat urinary tract infection (UTI) in afebrile men.
DESIGN, SETTING, AND PARTICIPANTS
Randomized, double-blind, placebo-controlled noninferiority trial of afebrile men with presumed symptomatic UTI treated with ciprofloxacin or trimethoprim/sulfamethoxazole at 2 US Veterans Affairs medical centers (enrollment, April 2014 through December 2019; final follow-up, January 28, 2020). Of 1058 eligible men, 272 were randomized.
INTERVENTIONS
Participants continued the antibiotic prescribed by their treating clinician for 7 days of treatment and were randomized to receive continued antibiotic therapy (n = 136) or placebo (n = 136) for days 8 to 14 of treatment.
MAIN OUTCOMES AND MEASURES
The prespecified primary outcome was resolution of UTI symptoms by 14 days after completion of active antibiotic treatment. A noninferiority margin of 10% was selected. The as-treated population (participants who took ≥26 of 28 doses and missed no more than 2 consecutive doses) was used for the primary analysis, and a secondary analysis included all patients as randomized, regardless of treatment adherence. Secondary outcomes included recurrence of UTI symptoms and/or adverse events within 28 days of stopping study medication.
RESULTS
Among 272 patients (median [interquartile range] age, 69 [62-73] years) who were randomized, 100% completed the trial and 254 (93.4%) were included in the primary as-treated analysis. Symptom resolution occurred in 122/131 (93.1%) participants in the 7-day group vs 111/123 (90.2%) in the 14-day group (difference, 2.9% [1-sided 97.5% CI, -5.2% to ∞]), meeting the noninferiority criterion. In the secondary as-randomized analysis, symptom resolution occurred in 125/136 (91.9%) participants in the 7-day group vs 123/136 (90.4%) in the 14-day group (difference, 1.5% [1-sided 97.5% CI, -5.8% to ∞]) Recurrence of UTI symptoms occurred in 13/131 (9.9%) participants in the 7-day group vs 15/123 (12.9%) in the 14-day group (difference, -3.0% [95% CI, -10.8% to 6.2%]; P = .70). Adverse events occurred in 28/136 (20.6%) participants in the 7-day group vs 33/136 (24.3%) in the 14-day group.
CONCLUSIONS AND RELEVANCE
Among afebrile men with suspected UTI, treatment with ciprofloxacin or trimethoprim/sulfamethoxazole for 7 days was noninferior to 14 days of treatment with regard to resolution of UTI symptoms by 14 days after antibiotic therapy. The findings support the use of a 7-day course of ciprofloxacin or trimethoprim/sulfamethoxazole as an alternative to a 14-day course for treatment of afebrile men with UTI.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT01994538.
Topics: Aged; Anti-Bacterial Agents; Ciprofloxacin; Double-Blind Method; Drug Administration Schedule; Duration of Therapy; Humans; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Urine
PubMed: 34313686
DOI: 10.1001/jama.2021.9899 -
Science Translational Medicine Dec 2021Although systemic antibiotics are critical in controlling infections and reducing morbidity and mortality, overuse of antibiotics is presumed to contribute to negative... (Randomized Controlled Trial)
Randomized Controlled Trial
Although systemic antibiotics are critical in controlling infections and reducing morbidity and mortality, overuse of antibiotics is presumed to contribute to negative repercussions such as selection of antimicrobial-resistant organisms and collateral damage to commensal microbes. In a prospective, randomized study of four clinically relevant antibiotic regimens [doxycycline (20 mg or 100 mg), cephalexin, or trimethoprim/sulfamethoxazole], we investigated microbial alterations on skin after administration of systemic antibiotics to healthy human volunteers. Samples from different skin and oral sites, as well as stool, were collected before, during, and up to 1 year after antibiotic use, and shotgun metagenomic sequencing was performed. Taxonomic analysis showed that subjects receiving doxycycline 100 mg and trimethoprim/sulfamethoxazole (TMP/SMX) exhibited greater changes to their skin microbial communities, as compared to those receiving other regimens or untreated controls. Oral and stool microbiota also demonstrated fluctuations after antibiotics. Bacterial culturing in combination with whole-genome sequencing revealed specific emergence, expansion, and persistence of antibiotic-resistant staphylococci harboring or and or genes in all subjects who received doxycycline 100 mg or TMP/SMX, respectively. Last, analysis of metagenomic data revealed an increase of genes involved in gene mobilization, indicating stress responses of microbes to antibiotics. Collectively, these findings demonstrate direct, long-lasting effects of antibiotics on skin microbial communities, highlighting the skin microbiome as a site for the development and persistence of antibiotic resistance and the risks of overprescribing.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Microbiota; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 34936382
DOI: 10.1126/scitranslmed.abd8077 -
Annals of the Rheumatic Diseases May 2023Severe infections contribute to morbidity and mortality in antineutrophil cytoplasm antibody-associated vasculitis (AAV). This study aimed to identify risk factors...
OBJECTIVES
Severe infections contribute to morbidity and mortality in antineutrophil cytoplasm antibody-associated vasculitis (AAV). This study aimed to identify risk factors associated with severe infections in participants of the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial.
METHODS
Data on 197 patients recruited into the RAVE trial were analysed. Participants received either rituximab (RTX) or cyclophosphamide (CYC), followed by azathioprine (AZA). Clinical and laboratory data of patients with and without severe infections (≥grade 3, according to the Common Terminology Criteria for Adverse Events version 3.0) were compared. Risk factors for severe infections were investigated using Cox-regression models.
RESULTS
Eighteen of 22 (82%) severe infections occurred within 6 months after trial entry, most commonly respiratory tract infections (15/22, 68%). At baseline, lower absolute numbers of CD19+ cells were observed in patients with severe infections either receiving RTX or CYC/AZA at baseline, while CD5+B and CD3+T cells did not differ between groups. In Cox-regression analysis, higher baseline serum immunoglobulin M levels were associated with the risk of severe infections, whereby a higher baseline total CD19+B cell number and prophylaxis against with trimethoprim-sulfamethoxazole (TMP/SMX) with decreased risk of severe infections. Use of TMP/SMX was associated with lower risk of severe infections in both groups, receiving either RTX or CYC/AZA.
CONCLUSIONS
The use of low-dose TMP/SMX is associated with reduced risk of severe infections in patients with AAV treated with either RTX or CYC/AZA. Reduced B cell subpopulations at start of treatment might be a useful correlate of reduced immunocompetence.
Topics: Humans; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination; Antibodies, Monoclonal, Murine-Derived; Remission Induction; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Cyclophosphamide; Azathioprine; Risk Factors; Treatment Outcome
PubMed: 36702528
DOI: 10.1136/ard-2022-223401 -
JAMA Network Open Oct 2020Oral β-lactam antibiotics are traditionally not recommended to treat Enterobacterales bacteremia because of concerns over subtherapeutic serum concentrations, but there...
IMPORTANCE
Oral β-lactam antibiotics are traditionally not recommended to treat Enterobacterales bacteremia because of concerns over subtherapeutic serum concentrations, but there is a lack of outcomes data, specifically after initial treatment with parenteral antibiotics. Given the limited data and increasing limitations of fluoroquinolones or trimethoprim-sulfamethoxazole (TMP-SMX), oral β-lactam antibiotics may be a valuable additional treatment option.
OBJECTIVE
To compare definitive therapy with oral β-lactam antibiotics vs fluoroquinolones or TMP-SMX for Enterobacterales bacteremia from a suspected urine source.
DESIGN, SETTING, AND PARTICIPANTS
A retrospective cohort study was conducted from January 1, 2007, to September 30, 2015, at 114 Veterans Affairs hospitals among 4089 adults with Escherichia coli, Klebsiella spp, or Proteus spp bacteremia and matching urine culture results. Additional inclusion criteria were receipt of active parenteral antibiotic(s) followed by conversion to an oral antibiotic. Exclusion criteria were previous Enterobacterales bacteremia, urologic abscess, or chronic prostatitis. Data were analyzed from April 15, 2019, to July 26, 2020.
EXPOSURES
Conversion of therapy to an oral β-lactam antibiotic vs fluoroquinolones or TMP-SMX after 1 to 5 days of parenteral antibiotics.
MAIN OUTCOMES AND MEASURES
The main outcome was a composite of either 30-day all-cause mortality or 30-day recurrent bacteremia. Propensity-based overlap weights were used to adjust for differences between groups. Log binomial regression models were used to estimate adjusted relative risks (aRRs) and adjusted risk differences (aRDs).
RESULTS
Of the 4089 eligible patients (3731 men [91.2%]; median age, 71 years [interquartile range, 63-81 years]), 955 received an oral β-lactam antibiotic, and 3134 received fluoroquinolones or TMP-SMX. The primary outcome occurred for 42 patients (4.4%) who received β-lactam antibiotics and 94 patients (3.0%) who received fluoroquinolones or TMP-SMX (aRD, 0.99% [95% CI, -0.42% to 2.40%]; aRR, 1.31 [95% CI, 0.87-1.95]). Mortality rates were 3.0% (n = 29) for patients receiving β-lactam antibiotics vs 2.6% (n = 82) for those receiving fluoroquinolones or TMP-SMX (aRD, 0.06% [95% CI, -1.13% to 1.26%]; aRR, 1.02 [95% CI, 0.67-1.56]). Recurrent bacteremia rates were 1.5% (n = 14) among those receiving β-lactam antibiotics vs 0.4% (n = 12) among those receiving fluoroquinolones or TMP-SMX (aRD, 1.03% [95% CI, 0.24%-1.82%]; aRR, 3.43 [95% CI, 0.42-27.90]).
CONCLUSIONS AND RELEVANCE
In this cohort study of adults with E coli, Klebsiella spp, or Proteus spp bacteremia from a suspected urine source, the relative risk of recurrent bacteremia was not significantly higher with β-lactam antibiotics compared with fluoroquinolones or TMP-SMX, and the absolute risk and risk difference were small (ie, <3%). No significant difference in mortality was observed. Oral β-lactam antibiotics may be a reasonable step-down treatment option, primarily when alternative options are limited by resistance or adverse effects. Further study is needed because statistical power was limited owing to a low number of recurrent bacteremia events.
Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Cohort Studies; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; beta-Lactams
PubMed: 33030555
DOI: 10.1001/jamanetworkopen.2020.20166 -
International Journal of Environmental... Dec 2022Phytoremediation is an environmentally friendly and economical method for removing organic contaminants from water. The purpose of the present study was to use for the...
Phytoremediation is an environmentally friendly and economical method for removing organic contaminants from water. The purpose of the present study was to use for the phytoremediation of water from sulfamethoxazole (SMX) and trimethoprim (TRI) residues. The experiment was conducted for 14 days, in which the loss of the pharmaceuticals in water and their concentration in plant tissues was monitored. Determination of SMX and TRI was conducted using liquid chromatography coupled with tandem mass spectrometry. The results revealed that various factors affected the removal of the contaminants from water, and their bioaccumulation coefficients were obtained. Additionally, the transformation products of SMX and TRI were identified. The observed decrease in SMX and TRI content after 14 days was 96.0% and 75.4% in water, respectively. SMX removal mainly involved photolysis and hydrolysis processes, whereas TRI was mostly absorbed by the plant. Bioaccumulation coefficients of the freeze-dried plant were in the range of 0.043-0.147 for SMX and 2.369-2.588 for TRI. Nine and six transformation products related to SMX and TRI, respectively, were identified in water and plant tissues. The detected transformation products stemmed from metabolic transformations and photolysis of the parent compounds.
Topics: Sulfamethoxazole; Trimethoprim; Hydrocharitaceae; Water; Water Pollutants, Chemical
PubMed: 36554877
DOI: 10.3390/ijerph192416994 -
Annals of Family Medicine Apr 2022Context: Rising antibiotic resistance has transcended hospital boundaries and impacted individuals with community acquired urinary tract infections (UTI). Scant data on...
Context: Rising antibiotic resistance has transcended hospital boundaries and impacted individuals with community acquired urinary tract infections (UTI). Scant data on antibiotic resistance in outpatient settings exists and most studies in the United States (U.S.) have identified predictors of resistance in acute-care settings. Objective: Determine the antibiogram among Escherichia coli isolates and factors associated with ciprofloxacin and trimethoprim-sulfamethoxazole (TMP-SMX) resistant gram-negative urinary isolates. Study Design: Retrospective cohort study. Setting: Two primary care, safety-net clinics in Houston, TX between 11/2018 and 3/2020. Population studied: Patients aged 18 and older presenting with provider suspected uncomplicated or complicated UTI. Outcome measures: Resistance and predictors of resistance to UTI-relevant antibiotics. Results: Among 1265 cultures collected, 372 (28.4%) were positive. We detected E. coli (50.3%) and Group B Streptococcus (18.6%) most frequently. Our patient population consisted mostly of Hispanic (75.7%) females (92.5%) born outside the U.S. (67.3%) with a mean age of 47. Among patients with E. coli isolated (n=189), antibiotic resistance was highest to ampicillin (63%), TMP-SMX (44%), ciprofloxacin (31%), and cefazolin (30%); no or low resistance against amikacin (0%), fosfomycin (0%), and nitrofurantoin (2.7%) was detected. Approximately 12% of E. coli isolates were extended-spectrum beta-lactamase positive. Having a prior UTI caused by a TMP-SMX resistant gram-negative organism and being born outside the U.S increased the odds of TMP-SMX resistance by 3.71 (95% confidence interval: 1.6-9.2) and 3.08 (95% CI: 1.6-6.3), respectively. Having a complicated UTI (odds ratio (OR): 3.58; 95% CI: 1.1-12.1), prior fluoroquinolone use (OR: 6.81; 95% CI: 1.7-34.1) and a prior UTI with ciprofloxacin resistance (OR: 7.84; 95% CI: 3.2-20.7) increased the odds of having a ciprofloxacin resistance. Conclusion: The Infectious Disease Society of America cautions against prescribing an antibiotic if regional resistance exceeds 20%. We constructed an antibiogram and found resistance surpassed this threshold for TMP-SMX and ciprofloxacin and identified factors associated with resistance to these agents. Assessing these characteristics during clinical decision making may improve antibiotic-organism susceptibility concordance in primary care.
Topics: Female; Humans; United States; Middle Aged; Male; Ciprofloxacin; Trimethoprim, Sulfamethoxazole Drug Combination; Escherichia coli; Retrospective Studies; Outpatients; Escherichia coli Infections; Drug Resistance, Bacterial; Urinary Tract Infections; Anti-Bacterial Agents; Microbial Sensitivity Tests
PubMed: 36944052
DOI: 10.1370/afm.20.s1.3177 -
Molecules (Basel, Switzerland) Oct 2019The presence of pharmaceutical compounds in the environment is a reality that calls for more efficient water treatment technologies. Photocatalysis is a powerful... (Review)
Review
The presence of pharmaceutical compounds in the environment is a reality that calls for more efficient water treatment technologies. Photocatalysis is a powerful technology available but the high energy costs associated with the use of UV irradiation hinder its large scale implementation. More sustainable and cheaper photocatalytic processes can be achieved by improving the sunlight harvesting and the synthesis of semiconductor/carbon composites has proved to be a promising strategy. Carbamazepine, diclofenac, and sulfamethoxazole were selected as target pharmaceuticals due to their recalcitrant behavior during conventional wastewater treatment and persistence in the environment, as properly reviewed. The literature data on the photocatalytic removal of carbamazepine, diclofenac, and sulfamethoxazole by semiconductor/carbon materials was critically revised to highlight the role of the carbon in the enhanced semiconductor performance under solar irradiation. Generally it was demonstrated that carbon materials induce red-shift absorption and they contribute to more effective charge separation, thus improving the composite photoactivity. Carbon was added as a dopant (C-doping) or as support or doping materials (i.e nanoporous carbons, carbon nanotubes (CNTs), graphene, and derived materials, carbon quantum dots (CQDs), and biochars) and in the large majority of the cases, TiO was the semiconductor tested. The specific role of carbon materials is dependent on their properties but even the more amorphous forms, like nanoporous carbons or biochars, allow to prepare composites with improved properties compared to the bare semiconductor. The self-photocatalytic activity of the carbon materials was also reported and should be further explored. The removal and mineralization rates, as well as degradation pathways and toxicity of the treated solutions were also critically analyzed.
Topics: Carbamazepine; Catalysis; Diclofenac; Graphite; Photochemical Processes; Semiconductors; Sulfamethoxazole; Sunlight; Water Pollutants, Chemical
PubMed: 31618947
DOI: 10.3390/molecules24203702 -
Critical Care Medicine Dec 2023Trimethoprim-sulfamethoxazole (TMP-SMX)-associated severe acute respiratory distress syndrome (ARDS) has gone underrecognized. We propose the first disease definition...
OBJECTIVES
Trimethoprim-sulfamethoxazole (TMP-SMX)-associated severe acute respiratory distress syndrome (ARDS) has gone underrecognized. We propose the first disease definition and clinical evaluation for a novel adverse drug reaction (ADR) based on a series of recently identified rare cases of life-threatening ADRs.
DESIGN
A retrospective study was conducted. All medical records were evaluated. Available pathology samples were sent to Massachusetts General for clinical consultation. Blood samples from surviving patients were obtained and human leukocyte antigen (HLA) analysis was performed by the Children's Mercy Hospital Genomic Center and Vanderbilt University Medical Center.
SETTING
U.S. ICUs, 1996-2021.
PATIENTS
Nineteen young patients (10-37) were identified. Patients were previously healthy, with no preexisting pulmonary disease, no other cause for respiratory failure, and no chronic history of smoking/vaping.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Through our retrospective analysis, we analyzed clinical characteristics associated with TMP-SMX. Pathology samples were reviewed, and HLA analysis was performed on available samples by the study team or as standard of care at treatment hospitals in some cases. In 19 critically ill patients, we identified a pattern of severe respiratory failure requiring ICU admission, mechanical ventilation, and frequent extracorporeal membrane oxygenation use. We describe the first three-part clinical diagnosis and evaluation strategy: 1) Clinical definition: Unexplained severe respiratory failure in a patient receiving greater than or equal to 6 days of TMP-SMX at treatment dose (not prophylaxis). TMP-SMX ARDS is a diagnosis of exclusion. 2) Genetic association: One hundred percent of currently available TMP-SMX respiratory failure patient genomic data, ( n = 11) have been carriers of both HLA-B*07:02 and HLA-C*07:02 alleles. HLA allele evaluation could be considered in patients with suspected TMP-SMX respiratory failure. 3) Lung pathology: A unique pulmonary pathologic pattern of lung injury termed diffuse alveolar injury with delayed epithelialization has been observed in these cases. In suspected cases, surgical lung biopsy early in the clinical course could be considered.
CONCLUSIONS
TMP-SMX is a commonly prescribed antibiotic. However, we find it imperative to share this relatively rare but life-threatening condition with clinicians as the mortality rate approaches 40%.
Topics: Child; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Retrospective Studies; Anti-Bacterial Agents; Respiratory Distress Syndrome; Respiratory Insufficiency
PubMed: 37449964
DOI: 10.1097/CCM.0000000000006002