Trimethoprim-sulfamethoxazole Group Research Articles

Therapeutic efficacy of compound organic acids administration on methicillin-resistant Staphylococcus aureus-induced arthritis in broilers

Avian arthritis is a common disease in the poultry industry, and the etiology is complex. Bacterial arthritis is usually caused by Staphylococcus aureus (S. aureus) infection. This study explored the minimum inhibitory concentration (MIC) of different organic acids against S. aureus MRSA85 and found that vanillic acid, suberic acid, itaconic acid, salicylic acid, and other organic acids had significant inhibitory effects on this strain, especially cinnamic acid, which exhibited the best inhibitory effect. The Fractional Inhibitory Concentration Index (FICI) test further revealed the synergistic effect among some compound organic acids, which can significantly enhance the antibacterial efficiency against MRSA85 while reducing the risk of bacterial resistance. Under the low concentrations (1/2 or 1/4 MIC) conditions, the MIC of the compound organic acids against S. aureus remains unchanged, and it can even enhance the sensitivity of antibiotic-resistant S. aureus to Oxacillin. Furthermore, the compound organic acids could effectively promote the recovery of S. aureus-induced arthritis in broiler models, reduce inflammatory responses, and lower down bacterial loads and inflammatory cytokine levels in joints, which indicated that the effects of the Compound 2 is comparable to that of the trimethoprim-sulfamethoxazole group. These results support the potential and application value of organic acids and their compounds, including Compound 1 to 3, as novel antibacterial agents in the treatment of S. aureus infections.

Low-Dose vs Conventional-Dose Trimethoprim-Sulfamethoxazole Treatment for Pneumocystis Pneumonia in Patients Not Infected With HIV: A Multicenter, Retrospective Observational Cohort Study

Trimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment for Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without HIV infection; 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. What is the efficacy and safety of low-dose TMP-SMX for non-HIV PCP compared with conventional-dose TMP-SMX after adjusting for patient background characteristics? In this multicenter retrospective cohort study, we included patients diagnosed with non-HIV PCP and treated with TMP-SMX between June 2006 and March 2021 at three institutions. The patients were classified into low-dose (TMP< 12.5mg/kg/d) and conventional-dose (TMP 12.5-20mg/kg/d) groups. The primary end point was 30-day mortality, and the secondary end points were 180-day mortality, adverse events grade 3 or higher per the Common Terminology Criteria for Adverse Events v5.0, and initial treatment completion rates. Background characteristics were adjusted using the overlap weighting method with propensity scores. Fifty-five patients in the low-dose group and 81 in the conventional-dose group were evaluated. In the overall cohort, the average age was 70.7 years, and the proportion of women was 55.1%. The average dose of TMP-SMX was 8.71mg/kg/d in the low-dose group and 17.78mg/kg/d in the conventional-dose group. There was no significant difference in 30-day mortality (6.7%vs18.4%, respectively; P= .080) or 180-day mortality (14.6%vs26.1%, respectively; P= .141) after adjusting for patient background characteristics. The incidence of adverse events, especially nausea and hyponatremia, was significantly lower in the low-dose group (29.8%vs59.0%, respectively; P= .005). The initial treatment completion rates were 43.3%and 29.6%in the low-dose and conventional-dose groups (P= .158), respectively. Survival was similar between the low-dose and conventional-dose TMP-SMX groups, and low-dose TMP-SMX was associated with reduced adverse events in patients with non-HIV PCP.

No Statistically Apparent Difference in Antifungal Effectiveness Observed Among Trimethoprim/Sulfamethoxazole Plus Clindamycin or Caspofungin, and Trimethoprim/Sulfamethoxazole Monotherapy in HIV-Infected Patients with Moderate to Severe Pneumocystis Pneumonia: Results of an Observational Multicenter Cohort Study.

IntroductionPneumocystis pneumonia is a common opportunistic infection in patients with HIV/AIDS, and is a leading cause of death in this population. Early selection of effective treatment is therefore critical to reduce mortality. We conducted a clinical trial to compare the effectiveness and safety of three different antifungal treatment regimens in HIV-infected patients with moderate to severe PCP.MethodsOur study was a multicenter, observational prospective clinical trial. We recruited 320 HIV-infected patients with moderate to severe PCP, and stratified these subjects into a trimethoprim/sulfamethoxazole (TMP-SMX) monotherapy group, a TMP-SMX plus clindamycin group, and a TMP-SMX plus caspofungin group. Patients were invited to participate in 12 weeks of follow-up. Outcomes included the difference in overall mortality and the proportion of overall positive response to treatment in the three groups at weeks 4 and 12, the difference in treatment duration, and the proportion of adverse events among the three groups during the study period.ResultsThe probability of survival not statistically different among three treatment groups. Mortality in the TMP-SMX monotherapy group (group 1) was 15/115 (13.04%) vs. 20/83 (24.10%) in the TMP-SMX plus clindamycin group (group 2) vs. 24/107 (22.43%) in the TMP-SMX plus caspofungin group (group 3) at week 12 (p = 0.092). The overall positive response rate to treatment in the three groups was 24.14%, 34.94%, and 38.32%, respectively, at week 4, and 33.91%, 38.55%, and 44.86%, respectively, at week 12. No significant difference in the overall positive response rate to treatment at either week 4 or week 12 was noted (p = 0.061, p = 0.246). Rates of changes to therapy were 6.50% (8/123) in group 1, 3.40% (3/87) in group 2, and 2.70% (3/110) in group 3, and did not differ significantly among the three groups (p = 0.376). There were also no significant differences in adverse events among the three treatment groups of patients with moderate to severe PCP.ConclusionsOur results indicate that there are no significant statistical differences among the three studied treatment regimens in terms of antifungal effectiveness in HIV-infected patients with moderate to severe PCP. TMP-SMX monotherapy is a convenient, cheap, and effective therapeutic drug regimen to treat HIV-infected patients with moderate to severe PCP, and is an appropriate treatment strategy in resource-limited settings.Clinical Trial Registrationwww.ClinicalTrials.gov, ID: ChiCTR1900021195. Registered on February 1, 2019.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00586-5.

Comparison of Trimethoprim-Sulfamethoxazole vs. Clindamycin for the Treatment of Children with Musculoskeletal Infections

Background: &#x0D; Musculoskeletal infections ([MSKI]; osteomyelitis, septic arthritis, pyomyositis) are common invasive infections in children. With increasing antibiotic resistance and allergies, treatment options are limited. Trimethoprim-sulfamethoxazole (TMP-SMX) has activity against common MSKI pathogens, yet pediatric MSKI outcomes data are limited. Our aim was to evaluate outcomes of children with MSKI treated with TMP-SMX compared to clindamycin. We hypothesized that outcomes would be similar between groups.&#x0D; Methods: &#x0D; We conducted a retrospective review of children &lt;18 years old, admitted to Riley Hospital for Children from January 2010-June 2021 treated with TMP-SMX or clindamycin for MSKI. Patients were identified by ICD-9/10 codes. Patients were excluded if TMP-SMX or clindamycin was not the main treatment, they had symptoms &gt;30 days, hardware associated infection, or an alternative diagnosis. Treatment success was defined as no evidence of infection at the end therapy. Treatment failure was defined as antibiotic intolerance, or development of recurrent/chronic osteomyelitis. Adverse drug reactions were recorded.&#x0D; Results:&#x0D; One-hundred-sixty-three patients (30 TMP-SMX, 133 clindamycin) met eligibility criteria. The majority were non-Hispanic white males, median age of 1.75 years (IQR, 1-3.75) for the TMP-SMX group, and 7 years (IQR 3-10) for the clindamycin group. Osteomyelitis was the most common infection type in both groups (TMP-SMX 43.3%, clindamycin 54.1%). S. aureus was the most common pathogen in both groups (TMP-SMX 36.7%, clindamycin 48.1%). Of the patients that completed follow-up, 84% successfully completed treatment with TMP-SMX, compared to 86.4% with clindamycin (odds ratio [OR] 0.82; 95% CI 0.25-2.46, p=0.75). Adverse drug reactions occurred in 6.7% of the TMP-SMX group, compared to 10.5% in the clindamycin group (OR 0.61; 95% CI 0.13-2.57, p=0.52).&#x0D; Conclusions:&#x0D; Preliminary results show that TMP-SMX is well tolerated and not associated with higher risk of treatment failure compared to clindamycin in the treatment of pediatric MSKI. Randomized controlled trials to evaluate optimal treatment are needed.

Valproic Acid Inhibits Chronic Toxoplasma Infection and Associated Brain Inflammation in Mice.

Individuals infected with Toxoplasma gondii are prone to psychobehavioral disorders, most notably schizophrenia and bipolar disorder. Valproic acid reportedly inhibits the proliferation of T. gondii tachyzoites in vitro. However, animals treated with the drug neither lived longer during acute infection nor had fewer brain cysts upon chronic infection. In this study, a quantitative real-time PCR (qPCR) method was applied to quantify copy numbers of BAG1 (a bradyzoite-specific protein), REP529 DNA (a repetitive DNA fragment of the parasite), and SAG1 (a highly expressed tachyzoite-specific surface protein) in the brains of chronically infected mice treated with valproic acid. The treatment inhibited the infection and decreased BAG1, SAG1, and REP529 copy numbers in mice brains (P < 0.0001), comparable to the effects of trimethoprim-sulfamethoxazole (TMP-SMZ), the common medication for toxoplasmosis treatment. Moreover, valproic acid decreased brain tumor necrosis factor alpha (TNF-α) expression (P < 0.0001) comparably to TMP-SMZ. Histological examination of mouse brains showed marked reductions in cyst establishment, perivascular infiltration of lymphocytes, and glial nodules to the same levels as those in the TMP-SMZ group. Our results provide direct evidence for the efficacy of valproic acid, a mood-stabilizing and antipsychotic drug, against chronic Toxoplasma infection. These results might help modulate therapeutic regimens for neuropsychiatric patients and aid in the design of more effective anti-Toxoplasma drugs.

Comparative effectiveness of trimethoprim-sulfamethoxazole versus atovaquone for the prophylaxis of pneumocystis pneumonia in patients with connective tissue diseases receiving prolonged high-dose glucocorticoids

We compared the prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) with atovaquone for pneumocystis pneumonia (PCP) in patients with connective tissue diseases (CTDs) receiving high-dose glucocorticoids. Patients with CTDs aged ≥ 18years who were treated with a prolonged course (≥ 4weeks) of glucocorticoids (≥ 20mg/day prednisone) in a Japanese tertiary center between 2013 and 2017 were included. The patients were categorized into two groups: TMP-SMX and atovaquone group. Adjusted cumulative incidence of PCP was compared between the two groups after propensity score weighting for differences in confounding factors. A total of 480 patients with a prolonged high-dose glucocorticoid treatment were identified. Out of 383 patients with TMP-SMX prophylaxis, 102 (26.8%) patients experienced adverse events leading to discontinuation within 4weeks of initiation, while no patient in the atovaquone discontinued the therapy. Two hundred eighty-one patients received TMP-SMX, while 107 received atovaquone for PCP prophylaxis. During a total of 397.0 person-years, 7 PCP cases (2 in the TMP-SMX, 5 in the atovaquone) occurred with a mortality rate of 54.5%. After adjusting for differences in baseline characteristics, the adjusted cumulative incidence of PCP was similar between the two group (HR 0.97, 95% CI 0.19-5.09, p = 0.97). Prophylactic effects for PCP in CTDs patients receiving prolonged high-dose glucocorticoids were similar between TMP-SMX and atovaquone. Atovaquone was well-tolerated with no side effects.

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.

Cotrimoxazole prophylaxis prevents major infective episodes in patients with systemic lupus erythematosus on immunosuppressants: A non-concurrent cohort study.

Prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) prevents pneumocystis jirovecii infection in SLE on immunosuppression. Its role in preventing other major infections in immuno suppressed SLE patients is unknown. A non-concurrent cohort study was conducted on patients of SLE fulfilling SLICC and/or ACR 1997 criteria, who received tapering dose of steroid starting with ≥0.5 mg/kg/day of prednisolone or equivalent dose of deflazacort and mycophenolate mofetil ≥1 g/day (or equivalent dose of mycophenolate sodium) at least for the preceding 1 year. Interviewing patients & documenting relevant data from hospital electronic Medical records (EMR), followed by comparison of Incidence densities of major infections between those on prophylactic Trimethoprim 160 mg + Sulfamethoxazole 800 mg and those not on it, was done by student 't' test. Multivariate logistic regression was performed for independent risk of any major infection between the two groups. Of 228 patients, 162 did not receive TMP-SMX prophylaxis, and 66 had received. The incidence density of major infection was found to be significantly lower in TMP-SMX group (1.25 per 100 person year) as compared to those not on TMP-SMX group (11.201 per 100 person year); P < 0.001 (95% CI 0.027 - 0.449) and odds ratio of 0.03 (CI 0 - 0.24). Cotrimoxazole prophylaxis in SLE patients on immunosuppression prevents major infections.

271. Clinical Outcomes Treating Gram-Negative Bacteremia with Oral Beta-Lactams vs. Trimethoprim-Sulfamethoxazole or Fluoroquinolone Step-Down Therapy

BackgroundRecently, studies about gram-negative bacteremia have shown that shorter courses and early step-down therapy with oral agents have equivalent outcomes compared to longer courses with intravenous therapy. The question remains, however, as to which oral agents may be most appropriate for oral conversion therapy. At Cone Health it has been common practice to de-escalate to oral beta-lactams due to local susceptibility patterns and safety concerns with fluoroquinolones. This study retrospectively evaluated the 30-day clinical outcomes of patients treated with oral beta-lactams as step-down therapy vs. fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX).MethodsIn this IRB approved, retrospective review, 200 patients with gram-negative rod bacteremia were screened. Sixty-seven patients were excluded due to inpatient mortality (17), transfer to another facility (7), hospice care (6), or receipt of intravenous antibiotics only (37). The most common organism isolated was E. coli at 57% (75/133) and a majority of cases had a genitourinary source, 79/133 (59%). The primary endpoints were 30-day readmission and mortality. Secondary endpoints included total length of antibiotic therapy and length of IV therapy.ResultsOf the 133 patients included, 101 (76%) received an oral beta-lactam and 32 (24%) received either a fluoroquinolone or TMP-SMX. In the beta-lactam group 22/101 (21.8%) were re-admitted within 30-days compared to 5/32 (15.6%) in the fluoroquinolone and TMP-SMX group (p=0.412). Each group had one patient re-admitted due to recurrence of bacteremia. The majority of patients in the beta-lactam group were re-admitted for a non-infectious reason (82%). Only 1 (1%) patient in the beta-lactam group died within 30 days of discharge compared to 2 (6%) in the fluoroquinolone group (p=0.165). Average total length of therapy in the beta-lactam group was 12.8 days compared to 14 days in the fluoroquinolone and TMP-SMX group (p=0.065). Average length of IV therapy was 3 days in the beta-lactam group and 4 days in the fluoroquinolone and TMP-SMX group (p=0.99).ConclusionAt our institution, we have not noted any significant difference in 30-day bacteremia recurrence or mortality between those who receive oral beta-lactams or fluoroquinolones/TMP-SMX.Disclosures All Authors: No reported disclosures

Long-term Results of Trimethoprim-Sulfamethoxazole Versus Placebo to Reduce the Risk of Recurrent Toxoplasma gondii Retinochoroiditis

To compare the effects of 1 year of treatment with trimethoprim-sulfamethoxazole (TMP-SMZ) vs placebo in reducing the risk of recurrence of toxoplasmic retinochoroiditis during a 6-year follow-up period. Randomized, double-masked clinical trial. This cohort included 141 subjects recruited in Campinas, Brazil. The inclusion criterion was unilateral active recurrent toxoplasmic retinochoroiditis. All subjects were treated with 1 dose of TMP-SMZ (160mg/800mg) twice daily for 45days, and all lesions healed after this treatment. After this initial treatment, subjects were randomly assigned to group 1 (1 TMP-SMZ dose every other day for 311days) or group 2 (1 identical placebo tablet containing starch with no active ingredients every other day for 311days). Between the second and sixth years of follow-up appointments, none of the subjects received treatment unless a new recurrence episode had occurred. The primary outcomes were recurrent toxoplasmic retinochoroiditis within the first year of follow-up and recurrent toxoplasmic retinochoroiditis in the 6 years of follow-up. The cumulative probability of recurrence 1, 2, 3, 4, 5, and 6 years after the initial infection was, respectively, 13.0% (9/69), 17.4% (12/69), 20.3% (14/69), 23.2% (16/69), 26.1% (18/69), and 27.5% (19/69) in the placebo group and 0%, 0%, 0%, 0%, 0%, and 1.4% (1/72) in the TMP-SMZ group (P < .001; log-rank test). There were 3 cases (3/69; 4.3%) of multiple recurrences in the same individual in the placebo group. No treatment-limiting toxicity or side effects were observed in either group. New recurrences were more frequent among female subjects. TMP-SMZ may be used safely for prophylaxis of recurrent toxoplasmic retinochoroiditis and may provide long-term benefits.

Anidulafungin as an alternative treatment for Pneumocystis jirovecii pneumonia in patients who cannot tolerate trimethoprim/sulfamethoxazole

Evidence supporting the use of an echinocandin alone as an alternative agent for the treatment of Pneumocystis jirovecii pneumonia (PCP) is limited and controversial. This retrospective cohort study was conducted at National Taiwan University Hospital from 1 July 2015 to 31 December 2017. Using multivariable Cox regression analyses, the outcomes of patients receiving trimethoprim/sulfamethoxazole (TMP-SMZ) or anidulafungin single therapy as an alternative treatment for PCP were investigated. A total of 207 patients with PCP were screened and 170 patients were included in the final analysis, among whom 134 (78.8%) received TMP-SMZ and 36 (21.2%) received anidulafungin as alternative anti-PCP treatment. Overall 60-day mortality was 34.1% (58/170), and 60-day mortality did not differ significantly between the anidulafungin group (38.9%; 14/36) and the TMP-SMZ group (32.8%; 44/134) (P=0.554). Age ≥60 years [hazard ratio (HR)=1.840, 95% confidence interval (CI) 1.039-3.259; P=0.036] and HIV infection (HR=0.102, 95% CI 0.013-0.771; P=0.027) independently predicted 60-day mortality. Patients with lower SpO2/FiO2 ratio (HR=0.994, 95% CI 0.990-0.998; P=0.005) showed a higher 60-day mortality. In the Kaplan-Meier survival analysis, anidulafungin as alternative anti-PCP treatment was not correlated with higher mortality (P=0.605). Using TMP-SMZ or anidulafungin as alternative anti-PCP treatment had similar 60-day mortality. These findings suggest that anidulafungin therapy may be an effective and alternative treatment for PCP in patients who cannot tolerate TMP-SMZ.

1977. Comparative Effectiveness of Linezolid vs. Trimethoprim–Sulfamethoxazole for Acute Bacterial Skin and Skin Structure Infections (ABSSSIs) at a Veterans Affairs Hospital

BackgroundLinezolid (LZD) and trimethoprim–sulfamethoxazole (TMP-SMX) are both used in the treatment of acute bacterial skin and skin structure infection (ABSSSI) with differing adverse event profiles to guide usage, but their comparative efficacies in severe ABSSSI remain unclear.MethodsThis retrospective cohort study evaluated patients admitted to the VA St. Louis Health Care System for treatment of an ABSSSI between April 18, 2000 and October 16, 2017 and discharged with a prescription for ≥5 days of LZD or TMP-SMX. The primary outcome was clinical failure, defined as a composite of an Emergency Department visit, clinic visit, inpatient admission, extension of antibiotics, change of antibiotic regimen for any reason, or the presence of an adverse reaction occurring in the 14 days after completion of the outpatient regimen. Adverse reactions evaluated were acute kidney injury, hyperkalemia, neutropenia, thrombocytopenia, and anemia. The secondary outcome evaluated risk factors for clinical failure with multivariate logistic regression analysis. Potential factors to be included in the analysis were drug choice, duration of intravenous antibiotic use while inpatient (<24 hours, ≥24 hours to ≤48 hours, >48 hours), identification of methicillin-resistant Staphylococcus aureus (MRSA) in culture, MRSA nasal colonization, and incision and drainage.ResultsA total of 139 patients were included in the analysis; 51 treated with LZD and 88 treated with TMP-SMX. Length of hospital stay was greater in the LZD group (6.05 days vs. 3.69 days [P = 0.023]), as was antibiotic use during hospitalization (98% [49/50] vs. 86% [77/90]; P = 0.019). The mean day supply of antibiotic dispensed at discharge was 10.18 in the LZD group and 9.64 in the TMP-SMX group (P = 0.48). Twenty-two percent (11/51) of patients treated with LZD and 18% (16/88) of those treated with TMP-SMX (P = 0.878) experienced clinical failure. Only receipt of antibiotics for 24–48 hours during hospitalization met criteria for inclusion in the multivariate analysis, but was not significantly associated with clinical failure (0.367 [95% CI 0.083–1.63]; P = 0.187).ConclusionThere was no difference in the rate of clinical failure between patients treated with LZD or TMP-SMX for severe ABSSSI.Disclosures All authors: No reported disclosures.

Effect of trimethoprim-sulfamethoxazole vs. norfloxacin on fecal E. coli resistance pattern and efficacy in patients receiving prophylaxis for spontaneous bacterial peritonitis

Background: Spontaneous Bacterial Peritonitis (SBP) is an infection of ascitic fluid. It is highly mortal and recurrent condition, so prophylaxis with Norfloxacin (NOR) or Trimethoprim-sulfamethoxazole (TMP-SMX) seems to play an important role in the prevention of further episodes of SBP. Aims of the study were to assess the effect of TMP-SMX/NOR on the sensitivity pattern of fecal E. coli after long term prophylaxis in Spontaneous Bacterial Peritonitis (SBP) and to compare the efficacy of TMP-SMX and NOR in prophylaxis of SBP.Methods: An interventional, prospective, open label, single center study conducted in Maulana Azad medical college, New Delhi, India. 52 patients of SBP or with high risk of SBP were screened and finally 39 patients were recruited. Stool sensitivity testing of fecal E. coli was done and they were divided into TMP-SMX group(n=18) and NOR group(n=21) according to sensitivity. After 45±3 days (7 weeks) their stool sample was re-examined for change sensitivity pattern of E. coli. Efficacy variables like any episode of SBP, fever (FEV) resolution of ascites (ASC), bacteremia (BACT), extraperitoneal infection (EPI), liver transplantation (LT) or death (D) were noted throughout the period of 24 weeks.Results: Resistance developed in 60% vs. 48% in TMP-SMX vs. NOR group(p=0.46) after 45 days of prophylaxis. By the end of 24 weeks, Incidence of SBP (29%vs. 25%, p&gt;0.99), episodes of FEV(P=0.60), EPI(p&gt;0.99), ASC(p&gt;0.99) and death (14% vs. 16%, p&gt;0.99) were almost similar in both the groups (TMP-SMX vs. NOR) respectively.Conclusions: Both TMP-SMX and NOR showed same degree of resistance and found equi-efficacious when administered as long-term prophylactic therapy in SBP. TMP-SMX can be a suitable as well as cost effective alternative to NOR for the prophylaxis of SBP.

Pyelonephritis treatment in the community emergency department: Cephalosporins vs. first-line agents

ObjectiveThe purpose of this study was to assess treatment with a fluoroquinolone or trimethoprim-sulfamethoxazole versus cephalosporins for pyelonephritis in discharged patients from a community hospital setting. MethodsA retrospective chart review was completed for adult female patients who received a prescription for a cephalosporin, fluoroquinolone or trimethoprim-sulfamethoxazole for the treatment of pyelonephritis within the network of a large healthcare system. The primary endpoint evaluated the failure rate of each treatment group. The secondary endpoint evaluated the difference between rates of resistance on culture and sensitivity reports for treatment groups. ResultsA total of 55 patients in the cephalosporin group and 43 patients in the fluoroquinolone and trimethoprim-sulfamethoxazole group were reviewed. The primary endpoint occurred in 0% of the patients in the cephalosporin group and in 23% of the patients in the fluoroquinolone and trimethoprim-sulfamethoxazole group, p < 0.001. Of the 98 urine samples collected, 71 samples were positive for pathogen growth. Upon evaluation of these isolates, 6% were resistant to cephalexin, 1% was resistant to cefdinir, 3% were resistant to ciprofloxacin and 23% were resistant to trimethoprim-sulfamethoxazole. Trimethoprim-sulfamethoxazole showed statistical significance for more bacterial resistance compared to the other agents, p < 0.01. ConclusionFailure of therapy for pyelonephritis occurred more often in the fluoroquinolone and trimethoprim-sulfamethoxazole group than in the cephalosporin group. The findings in this study are most applicable to patients who are treated on an outpatient basis. A prospective, randomized clinical trial is necessary to confirm these results.

Safety of the concomitant use of methotrexate and a prophylactic dose of trimethoprim-sulfamethoxazole.

The objective of this study was to investigate risk factors for cytopenia when a prophylactic dose of trimethoprim-sulfamethoxazole (TMP-SMX) was co-administered with methotrexate (MTX). Patients who received MTX with or without a prophylactic dose of TMP-SMX were included. Patients who received a therapeutic dose of TMP-SMX were excluded. The MTX-alone and MTX with TMP-SMX groups (MTX group and MTX + TMP-SMX group, respectively) were matched in a 4:1 ratio according to age, creatinine level, mean corpuscular volume and MTX dose. Cytopenia was defined as a haemoglobin level decrease by > 2g/dl, platelet count of < 150,000/mm3 or white blood cell count of < 3500/mm3. The Cox proportional hazards model was used to evaluate risk factors for cytopenia in patients administered with MTX. The incidence of cytopenia did not significantly differ between the MTX group and MTX + TMP-SMX group (5.0 vs 5.7%, p > 0.999). According to the Cox proportional hazards model, chronic liver disease (hazard ratio [HR] 5.829, 95% confidence interval [CI] 1.211-28.063, p = 0.028) was associated with an increased risk of cytopenia. However, the concomitant use of a prophylactic dose of TMP-SMX (HR 1.717, 95% CI 0.352-8.371, p = 0.504) was not significantly associated with an increased risk of cytopenia. Compared with the use of MTX alone, the concomitant use of MTX with a prophylactic dose of TMP-SMX was not significantly associated with an increased risk of cytopenia. Thus, a prophylactic dose of TMP-SMX can be safely used with MTX.

A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses

BackgroundUncomplicated skin abscesses are common, yet the appropriate management of the condition in the era of community-associated methicillin-resistant Staphylococcus aureus (MRSA) is unclear.MethodsWe conducted a multicenter, prospective, double-blind trial involving outpatient adults and children. Patients were stratified according to the presence of a surgically drainable abscess, abscess size, the number of sites of skin infection, and the presence of nonpurulent cellulitis. Participants with a skin abscess 5 cm or smaller in diameter were enrolled. After abscess incision and drainage, participants were randomly assigned to receive clindamycin, trimethoprim–sulfamethoxazole (TMP-SMX), or placebo for 10 days. The primary outcome was clinical cure 7 to 10 days after the end of treatment.ResultsWe enrolled 786 participants: 505 (64.2%) were adults and 281 (35.8%) were children. A total of 448 (57.0%) of the participants were male. S. aureus was isolated from 527 participants (67.0%), and MRSA was isolated from 388 (49.4%). Ten days after therapy in the intention-to-treat population, the cure rate among participants in the clindamycin group was similar to that in the TMP-SMX group (221 of 266 participants [83.1%] and 215 of 263 participants [81.7%], respectively; P=0.73), and the cure rate in each active-treatment group was higher than that in the placebo group (177 of 257 participants [68.9%], P<0.001 for both comparisons). The results in the population of patients who could be evaluated were similar. This beneficial effect was restricted to participants with S. aureus infection. Among the participants who were initially cured, new infections at 1 month of follow-up were less common in the clindamycin group (15 of 221, 6.8%) than in the TMP-SMX group (29 of 215 [13.5%], P=0.03) or the placebo group (22 of 177 [12.4%], P=0.06). Adverse events were more frequent with clindamycin (58 of 265 [21.9%]) than with TMP-SMX (29 of 261 [11.1%]) or placebo (32 of 255 [12.5%]); all adverse events resolved without sequelae. One participant who received TMP-SMX had a hypersensitivity reaction.ConclusionsAs compared with incision and drainage alone, clindamycin or TMP-SMX in conjunction with incision and drainage improves short-term outcomes in patients who have a simple abscess. This benefit must be weighed against the known side-effect profile of these antimicrobials. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00730028.)

Effect of Cephalexin Plus Trimethoprim-Sulfamethoxazole vs Cephalexin Alone on Clinical Cure of Uncomplicated Cellulitis

Emergency department visits for skin infections in the United States have increased with the emergence of methicillin-resistant Staphylococcus aureus (MRSA). For cellulitis without purulent drainage, β-hemolytic streptococci are presumed to be the predominant pathogens. It is unknown if antimicrobial regimens possessing in vitro MRSA activity provide improved outcomes compared with treatments lacking MRSA activity. To determine whether cephalexin plus trimethoprim-sulfamethoxazole yields a higher clinical cure rate of uncomplicated cellulitis than cephalexin alone. Multicenter, double-blind, randomized superiority trial in 5 US emergency departments among outpatients older than 12 years with cellulitis and no wound, purulent drainage, or abscess enrolled from April 2009 through June 2012. All participants had soft tissue ultrasound performed at the time of enrollment to exclude abscess. Final follow-up was August 2012. Cephalexin, 500 mg 4 times daily, plus trimethoprim-sulfamethoxazole, 320 mg/1600 mg twice daily, for 7 days (n = 248 participants) or cephalexin plus placebo for 7 days (n = 248 participants). The primary outcome determined a priori in the per-protocol group was clinical cure, defined as absence of these clinical failure criteria at follow-up visits: fever; increase in erythema (>25%), swelling, or tenderness (days 3-4); no decrease in erythema, swelling, or tenderness (days 8-10); and more than minimal erythema, swelling, or tenderness (days 14-21). A clinically significant difference was defined as greater than 10%. Among 500 randomized participants, 496 (99%) were included in the modified intention-to-treat analysis and 411 (82.2%) in the per-protocol analysis (median age, 40 years [range, 15-78 years]; 58.4% male; 10.9% had diabetes). Median length and width of erythema were 13.0 cm and 10.0 cm. In the per-protocol population, clinical cure occurred in 182 (83.5%) of 218 participants in the cephalexin plus trimethoprim-sulfamethoxazole group vs 165 (85.5%) of 193 in the cephalexin group (difference, -2.0%; 95% CI, -9.7% to 5.7%; P = .50). In the modified intention-to-treat population, clinical cure occurred in 189 (76.2%) of 248 participants in the cephalexin plus trimethoprim-sulfamethoxazole group vs 171 (69.0%) of 248 in the cephalexin group (difference, 7.3%; 95% CI, -1.0% to 15.5%; P = .07). Between-group adverse event rates and secondary outcomes through 7 to 9 weeks, including overnight hospitalization, recurrent skin infections, and similar infection in household contacts, did not differ significantly. Among patients with uncomplicated cellulitis, the use of cephalexin plus trimethoprim-sulfamethoxazole compared to cephalexin alone did not result in higher rates of clinical resolution of cellulitis in the per-protocol analysis. However, because imprecision around the findings in the modified intention-to-treat analysis included a clinically important difference favoring cephalexin plus trimethoprim-sulfamethoxazole, further research may be needed. clinicaltrials.gov Identifier: NCT00729937.

A Seven-Day Course of TMP-SMX May Be as Effective as a Seven-Day Course of Ciprofloxacin for the Treatment of Pyelonephritis

BackgroundThe Infectious Diseases Society of America guidelines recommend either 14 days of trimethoprim-sulfamethoxazole (TMP-SMX) or 7 days of ciprofloxacin for the treatment of pyelonephritis. Antibiotic courses of 7 days of TMP-SMX vs 7 days of ciprofloxacin for pyelonephritis have not been previously compared. We evaluated the odds of a subsequent, symptomatic urinary tract infection (UTI) for women with Escherichia coli pyelonephritis receiving a 7-day course of TMP-SMX vs a 7-day course of ciprofloxacin. MethodsWomen ages 16 years and older with E. coli pyelonephritis presenting to 5 health care facilities in the greater Maryland area between 2010 and 2016 receiving either TMP-SMX or ciprofloxacin were included. Patients were excluded if they met any of the following criteria: (a) pregnancy, (b) dialysis dependency, (c) E. coli not susceptible to the treatment prescribed, (d) polymicrobial urine culture, or (e) >48 hours of antibiotic therapy other than TMP-SMX or ciprofloxacin. ResultsOf 272 women meeting eligibility criteria, 81 (30%) and 191 (70%) received 7 days of TMP-SMX and 7 days of ciprofloxacin, respectively. In an adjusted model, the likelihood of a recurrent UTI within 30 days for the TMP-SMX and ciprofloxacin groups was similar (adjusted odds ratio 2.30; 95% confidence interval, 0.72-7.42). ConclusionsOur findings suggest that 7 days of TMP-SMX therapy may result in similar clinical outcomes compared with 7 days of ciprofloxacin for the treatment of pyelonephritis. Considering the frequency of pyelonephritis and risks of antibiotic resistance and associated toxicities, decreasing the duration of antibiotic therapy for pyelonephritis may impact a large number of women.

Weight Gain and Obesity in Infants and Young Children Exposed to Prolonged Antibiotic Prophylaxis

An association between antibiotic use and excessive weight gain or obesity in healthy infants and young children has been reported, but evidence is inconsistent and based on observational studies of growth in relation to incidental antibiotic exposures. To evaluate whether prolonged antibiotic exposure is associated with weight gain in children participating in a clinical trial of antibiotic prophylaxis to prevent recurrent urinary tract infection. Secondary analysis of data from the Randomized Intervention for Children With Vesicoureteral Reflux Study, a 2-year randomized clinical trial that enrolled participants from 2007 to 2011. All 607 children who were randomized to receive antibiotic (n = 302) or placebo (n = 305) were included. Children with urinary tract anomalies, premature birth, or major comorbidities were excluded from participation. Trimethoprim-sulfamethoxazole or placebo taken orally, once daily, for 2 years. Weight gain as measured by change in weight-for-age z score from baseline to the end-of-study visit at 24 months. Secondary outcomes included weight gain at 6, 12, and 18 months and the prevalence of overweight or obesity at 24 months. Participants had a median age of 12 months (range, 2-71 months) and 558 of 607 (91.9%) were female. Anthropometric data were complete at the 24-month visit for 428 children (214 in the trimethoprim-sulfamethoxazole group and 214 in the placebo group). Weight gain in the trimethoprim-sulfamethoxazole group and the placebo group was similar (mean [SD] change in weight-for-age z score: +0.14 [0.83] and +0.18 [0.85], respectively; difference, -0.04 [95% CI, -0.19 to 0.12]; P = .65). There was no significant difference in weight gain at 6, 12, or 18 months or in the prevalence of overweight or obesity at 24 months (24.8% vs 25.7%; P = .82). Subgroup analyses showed no significant interaction between weight gain effect and age, sex, history of breastfeeding, prior antibiotic use, adherence to study medication, or development of urinary tract infection during the study. Based on a secondary analysis of data from a large clinical trial of trimethoprim-sulfamethoxazole prophylaxis, there was no evidence that prolonged exposure to this antibiotic has a concurrent effect on weight gain or the prevalence of overweight or obesity in healthy infants and young children.

Trimethoprim-Sulfamethoxazole Versus Placebo in Reducing the Risk of Toxoplasmic Retinochoroiditis Recurrences: A Three-Year Follow-up

To compare the effects of 1 year of treatment with trimethoprim/sulfamethoxazole (TMP-SMZ) vs a placebo in reducing the risk of toxoplasmic retinochoroiditis recurrences during a 3-year follow-up period. Randomized, double-masked clinical trial. This cohort included 141 volunteers recruited in Campinas, Brazil. Inclusion criterion was unilateral active recurrent toxoplasmic retinochoroiditis. All volunteers were treated with 1 tablet of TMP-SMZ (160 mg/800 mg) twice daily for 45days, and all lesions healed after this treatment. After this initial treatment, the volunteers were randomly assigned to Group 1(1TMP-SMZ tablet every 2days for 311days) or Group 2 (1 identical placebo tablet containing starch with no active ingredients every 2days for 311days). At the second- and third-year follow-up appointments, none of the volunteers received treatment unless a new recurrence episode had occurred. The primary outcomes were recurrent toxoplasmic retinochoroiditis within the first year of follow-up and recurrent toxoplasmic retinochoroiditis within the third year of follow-up. The cumulative probability of recurrence at 1, 2, and 3 years of follow-up were, respectively, 13.0% (9/69), 17.4% (12/69), and 20.3% (14/69) in the placebo group and 0% (0/72) in the TMP-SMZ group (P < .001, log-rank test). There was no case of multiple recurrences in the same individual. No treatment-limiting toxicity or side effects were observed in either group. New recurrences were more frequent among female volunteers. TMP-SMZ may be used safely for prophylaxis of recurrent toxoplasmic retinochoroiditis, with long-term benefits.