Bacteriological Response Research Articles

Impact of Vancomycin trough levels monitoring on uncomplicated methilcillin-resistant Staphylococcus aureus bacteremia in chronic kidney disease on hemodialysis, retrospective cohort

BackgroundCKD patients on hemodialysis (HD) with Staphylococcus aureus (SA) bacteremia present high morbidity, mortality and increased risk of MRSA. Vancomycin is the antibiotic of choice in these cases, it has a narrow therapeutic margin and inadequate dosage generates a risk of toxicity, therefore, the recommendation is to dosage it through serum levels.MethodsThis is a retrospective cohort study in 3 hospitals of third level of complexity in the city of Medellin in which there were differences in the measurement and implementation of vancomycin25 dosage based on trough levels (VL) in patients with chronic kidney disease on hemodialysis (CKD- HD) with uncomplicated bacteremia based infection by methilcillin-resistant Staphyloccocus aureus (MRSA). The primary outcome was the composite of hospital mortality, clinical response (fever, hemodynamic instability and altered consciousness), complications associated with bacteremia, or bacteriological response failure (positive cultures at first week follow-up) at 7 days. The composite variables were analyzed individually as secondary outcomes.ResultsThe main unadjusted outcome (OR 1.3, CI 0.6 - 2.7) and adjusted for age, Charlson index, loading dose, initial dose, dosing frequency and MIC to vancomycin (OR 1.2, CI 0.5 - 2.7). Regarding adjusted secondary outcomes: clinical response (OR 1.4 CI 0.3 - 5.8), death (OR 1.3 CI 0.3 - 4.6) and complications (OR 0.9, CI 0.37 - 2.2).ConclusionsWe conclude that the measurement of trough levels in patients with HD-CKD does not modify the composite outcome. The main limitation is the sample size and type of study, randomized control trials may be required to confirm the results presented.

The Clinical Efficacy of Multidose Oritavancin: A Systematic Review.

Oritavancin (ORI) is a semisynthetic lipoglycopeptide approved as a single 1200 mg dose intravenous infusion for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by Gram-positive organisms in adults. The pharmacokinetic/pharmacodynamic (PK/PD) linear kinetic profile and long terminal half-life (~393 h) of ORI make it therapeutically attractive for the treatment of other Gram-positive infections for which prolonged therapy is needed. Multidose regimens are adopted in real-world clinical practice with promising results, but aggregated efficacy data are still lacking. A comprehensive search on PubMed/Medline, Scopus, Cochrane and Google Scholar databases was performed to include papers published up to the end of January 2023. All articles on ORI multiple doses usage, including case reports, with quantitative data and relevant clinical information were included. Two reviewers independently assessed papers against the inclusion/exclusion criteria and for methodological quality. Differences in opinion were adjudicated by a third party. From 1751 potentially relevant papers identified by this search, a total of 16 studies met the inclusion criteria and were processed further in the final data analysis. We extracted data concerning clinical response, bacteriologic response, mortality and adverse events (AEs). From the 16 included papers, 301 cases of treatment with multidose ORIs were identified. Multidose regimens comprised an initial ORI dose of 1200 mg followed by 1200 mg or 800 mg subsequent doses with a varying total number and frequency of reinfusions. The most often treated infections and isolates were osteomyelitis (148; 54.4%), ABSSSI (35; 12.9%) and cellulitis (14; 5.1%); and MRSA (121), MSSA (66), CoNS (17), E. faecalis (13) and E. faecium (12), respectively. Clinical cure and improvement by multidose ORI regimens were observed in 85% (231/272) and 8% (22/272) patients, respectively. Multidose ORI was safe and well tolerated; the most frequent AEs were infusion-related reactions and hypoglycemia. A multidose ORI regimen may be beneficial in treating other Gram-positive infections besides ABSSSIs, with a good safety profile. Further studies are warranted to ascertain the superiority of one multidose ORI scheme or posology over the other.

English

The 24-h area under the curve concentration (AUC24 h) is associated with better clinical and bacteriological response to vancomycin in patients with methicillin-resistant Staphylococcus aureus who achieve the target AUC24 h between 400 and 700 mg×h/L. Recent consensus recommends maintaining trough concentrations between 15 and 20 mg/mL as a convenient target  to reach an AUC/minimum inhibitory concentration (MIC) ≥ 400. The aim of this study was to determine the correlation between a calculated AUC24 h and a measured trough vancomycin concentration (C0). We conducted a retrospective observational study. Hospitalized patients prescribed vancomycin for a presumed or documented invasive staphylococcal infections were evaluated. A formula based on the relationship between dose, vancomycin clearance and creatinine clearance was used to determine each patient's AUC24 h. 161 patients were included in the study. Median age was 34 years. The mean daily dose of vancomycin was 28 mg/kg/day. The median vancomycin C0 was 12.2 mg/mL, 17.3% were in the therapeutic range. The median AUC was 246.84 mg×h/L, only 8% achieved the target AUC24 h between 400 and 700 mg×h/L. Of these, 3 patients had C0 between 15 and 20 mg/mL and 9 patients had C0> 20 mg/mL. A poor correlation was found between C0 and AUC24 h = 0.37; r2 = 0.14; p<0.0001. In conclusion, vancomycin C0 correlated poorly with AUC24/MIC targets. C0 seems to underestimate AUC24 h. So, a patient specific AUC24/MIC may serve to predict efficacy while C0 can be used as indicators of possible nephrotoxicity and development of resistance. Key words: Vancomycin, area under the curve (AUC), trough concentration, minimum inhibitory concentration, therapeutic drug monitoring.

Efficacy of Five Days Nitrofurantoin Therapy versus Fosfomycin Stat Dose in Clinical Resolution of Uncomplicated Urinary Tract Infections

Objective: To compare the efficacy of 5-days Nitrofurantoin therapy versus Fosfomycin stat dose in clinical resolution of uncomplicated urinary tract infections in females of reproductive age group.
 Study Design: Comparative prospective study.
 Place and Duration of Study: Department of Medicine, Pak Emirates Military Hospital, Rawalpindi Pakistan, from Apr 2019 to Mar 2020.
 Methodology: A total of 498 females of reproductive age (18 years to 40 years) with lower urinary tract infection symptoms(increased urinary hesitancy, frequent micturition, tenderness at suprapubic region) and positive urine dipstick test for nitrates/leukocyte esterase test were incorporated in the study. Patients were randomly assigned to Group-A and Group-B,comprising 249 patients. Group-A was given tablet Nitrofurantoin 100mg every six hourly. Group-B was given Fosfomycin 3gstat dose. Patients were advised to follow up on days 14 and 28 of treatment to observe the clinical resolution of urinary tractinfection symptoms and bacteriologic response.
 Results: Clinical resolution of urinary tract infection on the 28th day of treatment was attained in 172(69.1%) patients of the Nitrofurantoin-Group versus 140(56.2%) patients receiving Fosfomycin (p-value 0.003). Baseline urine cultures were positive in 286(57.4%) patients. Microbiologic resolution was achieved in 109 of 140(77.9%) and 100 of 146(68.4%) (p- value=0.026).
 Conclusion: Among the females of reproductive age, five days of Nitrofurantoin therapy is superior to stat dose Fosfomycin in the clinical and microbiologic resolution of uncomplicated urinary tract infections.

611. Meropenem Dosage Optimization in Critically Ill Patients Based on a Population Pharmacokinetic Approach.

Abstract Background Meropenem (MRP) is commonly used to treat serious infections and displays wide variability in plasma concentrations after administration of the same dose in critically ill patients due to factors that affect MRP volume of distribution (V) and clearance (CL) (e.g. edema, sepsis, kidney failure). These alterations could lead to not achieve the pharmacokinetic/pharmacodinamic (PK/PD) target with the consequent failure of antibacterial therapy. The aim of this study was to describe MRP pharmacokinetic parameters in critically ill patients in order to establish safe and effective initial dosing regimens adapted to patients characteristics. Methods This prospective observational study enrolled 78 critically ill patients receiving MRP based on the clinical, biochemical and microbiological findings. Blood sampling occurred at pre-dose, 1, 3 and 6h post-dose. MRP plasma concentrations were determined by high-performance liquid chromatography. Population pharmacokinetic modelling and Monte Carlo simulations were executed with NONMEM. Several regimen dosages of MRP under different scenarios were simulated in order to achieve high probability of target attainment (PTA > 90%) for PK/PD targets of %t > CMI 50% and 100%. Results In critically-ill Mexican patients, MRP PK were best described by a one compartment model. The final population model was: CL (L/h) = 11.9 ∗ (CLCr/102.23) and V (L) = 25.2. Final model was internally validated proving that it was stable and showed an adequate estimation of variability. Precision and bias fit were assessed through external validation comparing the predictive performance of the base and final models. Different initial dosage regimens were found for CLCr values in which the clinician can choose between a lower dose, a longer dosage interval or a shorter infusion time. However, for patients with augmented renal clearance or PK/PD target 100%t > MIC it was observed that no regimen complied PTA > 90%, suggesting a continuous infusion would be more appropriate. Conclusion This study demonstrates the wide variability in MRP pharmacokinetics and enhances the need to include therapeutic drug monitoring as part of stewardships interventions in critically ill patients to maximize bacteriological and clinical responses. Disclosures All Authors: No reported disclosures.

Bedaquiline resistance probability to guide treatment decision making for rifampicin-resistant tuberculosis: insights from a qualitative study

BackgroundBedaquiline (BDQ) is a core drug for rifampicin-resistant tuberculosis (RR-TB) treatment. Accurate prediction of a BDQ-resistant phenotype from genomic data is not yet possible. A Bayesian method to predict BDQ resistance probability from next-generation sequencing data has been proposed as an alternative.MethodsWe performed a qualitative study to investigate the decision-making of physicians when facing different levels of BDQ resistance probability. Fourteen semi-structured interviews were conducted with physicians experienced in treating RR-TB, sampled purposefully from eight countries with varying income levels and burden of RR-TB. Five simulated patient scenarios were used as a trigger for discussion. Factors influencing the decision of physicians to prescribe BDQ at macro-, meso- and micro levels were explored using thematic analysis.ResultsThe perception and interpretation of BDQ resistance probability values varied widely between physicians. The limited availability of other RR-TB drugs and the high cost of BDQ hindered physicians from altering the BDQ-containing regimen and incorporating BDQ resistance probability in their decision-making. The little experience with BDQ susceptibility testing and whole-genome sequencing results, and the discordance between phenotypic susceptibility and resistance probability were other barriers for physicians to interpret the resistance probability estimates. Especially for BDQ resistance probabilities between 25% and 70%, physicians interpreted the resistance probability value dynamically, and other factors such as clinical and bacteriological treatment response, history of exposure to BDQ, and resistance profile were often considered more important than the BDQ probability value for the decision to continue or stop BDQ. In this grey zone, some physicians opted to continue BDQ but added other drugs to strengthen the regimen.ConclusionsThis study highlights the complexity of physicians' decision-making regarding the use of BDQ in RR-TB regimens for different levels of BDQ resistance probability.. Ensuring sufficient access to BDQ and companion drugs, improving knowledge of the genotype–phenotype association for BDQ resistance, availability of a rapid molecular test, building next-generation sequencing capacity, and developing a clinical decision support system incorporating BDQ resistance probability will all be essential to facilitate the implementation of BDQ resistance probability in personalizing treatment for patients with RR-TB.

Pulmonary Non-tuberculous Mycobacterial Infections in Category II Failures from National Tuberculosis Programme

Pulmonary infections due to non-tuberculous mycobacteria (NTM) are increasingly being reported. These can mimic drug-resitant tubercuolosis. A diagnosis of NTM infections needs a high degree of clinical suspicion and repeated isolation of the organism on culture. NTM infections occur commonly in immunocompromised individuals and in people with lung abnormalities. Currently there are no guidelines on drug combinations and the duration of treatment is not adequately defined. Two cases of pulmonary infection with NTM in immune-competent individuals are described in the present report. Although the bacteriological, radiological and clinical response to treatment was good; early discontinuation of treatment resulted in recurrence and change in drug susceptibility pattern, suggesting the need for prolonged treatment for achieving cure.

Sequencing Mycobacteria and Algorithm-determined Resistant Tuberculosis Treatment (SMARTT): a study protocol for a phase IV pragmatic randomized controlled patient management strategy trial

BackgroundRifampicin-resistant tuberculosis (RR-TB) remains an important global health problem. Ideally, the complete drug-resistance profile guides individualized treatment for all RR-TB patients, but this is only practised in high-income countries. Implementation of whole genome sequencing (WGS) technologies into routine care in low and middle-income countries has not become a reality due to the expected implementation challenges, including translating WGS results into individualized treatment regimen composition.MethodsThis trial is a pragmatic, single-blinded, randomized controlled medical device trial of a WGS-guided automated treatment recommendation strategy for individualized treatment of RR-TB. Subjects are 18 years or older and diagnosed with pulmonary RR-TB in four of the five health districts of the Free State province in South Africa. Participants are randomized in a 1:1 ratio to either the intervention (a WGS-guided automated treatment recommendation strategy for individualized treatment of RR-TB) or control (RR-TB treatment according to the national South African guidelines). The primary effectiveness outcome is the bacteriological response to treatment measured as the rate of change in time to liquid culture positivity during the first 6 months of treatment. Secondary effectiveness outcomes include cure rate, relapse rate (recurrence of RR-TB disease) and TB free survival rate in the first 12 months following RR-TB treatment completion. Additional secondary outcomes of interest include safety, the feasibility of province-wide implementation of the strategy into routine care, and health economic assessment from a patient and health systems perspective.DiscussionThis trial will provide important real-life evidence regarding the feasibility, safety, cost, and effectiveness of a WGS-guided automated treatment recommendation strategy for individualized treatment of RR-TB. Given the pragmatic nature, the trial will assist policymakers in the decision-making regarding the integration of next-generation sequencing technologies into routine RR-TB care in high TB burden settings.Trial registrationClinicalTrials.gov NCT05017324. Registered on August 23, 2021.

Clinical validation of the two-point method for predicting vancomycin AUC based on peak and trough plasma concentrations.

Vancomycin area under the curve/minimum inhibitory concentration (AUC/MIC) has been proposed as a therapeutic drug monitoring (TDM) target to dose vancomycin. It is time-consuming to estimate AUCs using traditional methods. A two-point trough-peak method is more straightforward for calculating the vancomycin AUC. However, the technique and the AUC/MIC target have not been validated in Chinese patients. To compare the clinical outcomes of vancomycin therapy in Chinese older adults (aged > 60years) between the trough-only and the two-point peak-trough AUC TDM approaches. The patients were divided into study and control groups according to TDM approaches. A trough-based TDM was used in the control group (target trough level 15-20mg/L). Stanford University has provided a method to predict vancomycin AUC using peak-valley concentration alone (two-point method). A two-point trough-peak TDM approach was employed in the study group (target AUC/MIC ≥ 400). The effect of vancomycin was evaluated in terms of clinical findings, laboratory values, and bacteriologic responses. The effects of treatment and kidney functions were compared between the two groups. A total of 389 patients met the study inclusion criteria, and 189 were excluded based on the exclusion criteria. Of the 200 patients, 80 received the two-point TDM approach (the study group), and 120 were monitored using the trough-based approach (the control group). The average age was 69.8 ± 7.1years. Staphylococcus aureus (34%) was the most common Gram-positive bacteria. No vancomycin-related nephrotoxicity was observed in either group. The percentages of patients with an excellent response to vancomycin therapy were significantly higher in the study group than in the control group, 90% (72/80) versus 73.3% (88/120),P = 0.0039. The two-point peak-trough method is practical for obtaining vancomycin AUC. The AUC/MIC ≥ 400 target demonstrates treatment effectiveness and safety in older Chinese patients.

Appropriate Use of Glycopeptide Antibiotics and Therapeutic Drug Monitoring for Invasive Infections

Vancomycin and teicoplanin are representative glycopeptide antibiotics with activities against gram-positive cocci. The area under the drug concentration–time curve (AUC)/minimal inhibitory concentration (MIC) has been extensively used as an indicator of the bacteriological response to glycopeptide antibiotics, and the trough concentration has been used as a surrogate marker for the AUC/MIC. However, the guidelines for therapeutic drug monitoring (TDM) are being revised in accordance with increasing pharmacokinetic understanding of glycopeptide antibiotics. This review describes the pharmacokinetic/pharmacodynamic characteristics of glycopeptide antibiotics and discusses their optimal use with appropriate TDM.

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

Periodontitis is an inflammatory disease characterized by the destruction of the periodontium. In the last decade, a new murine model of periodontitis has been widely used to simulate alveolar bone resorption and periodontal soft tissue destruction by ligation. Typically, 3-0 to 9-0 silks are selected for ligation around the molars in mice, and significant bone loss and inflammatory infiltration are observed within a week. The ligature-maintained period can vary according to specific aims. We reviewed the findings on the interaction of systemic diseases with periodontitis, periodontal tissue destruction, the immunological and bacteriological responses, and new treatments. In these studies, the activation of osteoclasts, upregulation of pro-inflammatory factors, and excessive immune response have been considered as major factors in periodontal disruption. Multiple genes identified in periodontal tissues partly reflect the complexity of the pathogenesis of periodontitis. The effects of novel treatment methods on periodontitis have also been evaluated in a ligature-induced periodontitis model in mice. This model cannot completely represent all aspects of periodontitis in humans but is considered an effective method for the exploration of its mechanisms. Through this review, we aimed to provide evidence and enlightenment for future studies planning to use this model.

Effectiveness of Pharmacokinetic/Pharmacodynamic-Guided Meropenem Treatment in Critically Ill Patients: A Comparative Cohort Study.

The proper dosage of antibiotics is a key element in the effective treatment of infection, especially in critically ill patients. This study aimed to evaluate the efficacy of optimized meropenem regimens based on pharmacokinetic/pharmacodynamic criteria in patients admitted to the intensive care unit. This observational, naturalistic, retrospective, unicentric cohort study was performed between May 2011 and December 2017. The clinical and bacteriologic responses of 77 control intensive care unit patients receiving meropenem were compared with those of 77 propensity score-balanced patients who received meropenem dose adjusted by therapeutic drug monitoring. The primary end point of clinical response was a reduction at the end of treatment of at least 80% of the maximum procalcitonin (PCT) value recorded during the meropenem treatment. The primary end point was met by 55 patients (71.4%) in the adjusted group compared with 41 (53.3%) patients in the control group (mean difference 18.1%, P = 0.02). Fifty-one patients (66.2%) in the adjusted group required a meropenem dose adjustment, being necessary in 46 of them (90.2%) to decrease the dose. The reduction of PCT was the greatest in the adjusted group compared with the unadjusted group (93% versus 85%, P = 0.004); a greater percentage of patients reached a PCT level < 0.5 ng/mL (63.6% versus 41.6%, P = 0.006), and there was a trend toward an improved bacteriologic response (relative risk = 1.27; 95% confidence interval: 0.92-1.56). There were no differences in early mortality or safety between groups. Adjustment of meropenem therapy by monitoring is a useful strategy for improving meropenem effectiveness in the treatment of infection in critically ill patients, with no impact on safety.

Failure of target attainment of beta-lactam antibiotics in critically ill patients and associated risk factors: a two-center prospective study (EXPAT)

BackgroundEarly and appropriate antibiotic dosing is associated with improved clinical outcomes in critically ill patients, yet target attainment remains a challenge. Traditional antibiotic dosing is not suitable in critically ill patients, since these patients undergo physiological alterations that strongly affect antibiotic exposure. For beta-lactam antibiotics, the unbound plasma concentrations above at least one to four times the minimal inhibitory concentration (MIC) for 100% of the dosing interval (100%ƒT > 1–4×MIC) have been proposed as pharmacodynamic targets (PDTs) to maximize bacteriological and clinical responses. The objectives of this study are to describe the PDT attainment in critically ill patients and to identify risk factors for target non-attainment.MethodsThis prospective observational study was performed in two ICUs in the Netherlands. We enrolled adult patients treated with the following beta-lactam antibiotics: amoxicillin (with or without clavulanic acid), cefotaxime, ceftazidime, ceftriaxone, cefuroxime, and meropenem. Based on five samples within a dosing interval at day 2 of therapy, the time unbound concentrations above the epidemiological cut-off (ƒT > MICECOFF and ƒT > 4×MICECOFF) were determined. Secondary endpoints were estimated multivariate binomial and binary logistic regression models, for examining the association of PDT attainment with patient characteristics and clinical outcomes.ResultsA total of 147 patients were included, of whom 63.3% achieved PDT of 100%ƒT > MICECOFF and 36.7% achieved 100%ƒT > 4×MICECOFF. Regression analysis identified male gender, estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2, and high body mass index (BMI) as risk factors for target non-attainment. Use of continuous renal replacement therapy (CRRT) and high serum urea significantly increased the probability of target attainment. In addition, we found a significant association between the 100%ƒT > MICECOFF target attainment and ICU length of stay (LOS), but no significant correlation was found for the 30-day survival.ConclusionsTraditional beta-lactam dosing results in low target attainment in the majority of critically ill patients. Male gender, high BMI, and high eGFR were significant risk factors for target non-attainment. These predictors, together with therapeutic drug monitoring, may help ICU clinicians in optimizing beta-lactam dosing in critically ill patients.Trial registrationNetherlands Trial Registry (EXPAT trial), NTR 5632. Registered on 7 December 2015.

4-month moxifloxacin containing regimens in the treatment of patients with sputum-positive pulmonary tuberculosis in South India - a randomised clinical trial.

Shortening tuberculosis (TB) treatment duration is a research priority. We tested the efficacy and safety of 3- and 4-month regimens containing moxifloxacin in a randomised clinical trial in pulmonary TB (PTB) patients in South India. New, sputum-positive, adult, HIV-negative, non-diabetic PTB patients were randomised to 3- or 4-month moxifloxacin regimens [moxifloxacin (M), isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E)] or to a control regimen (2H3 R3 Z3 E3 /4R3 H3 ) [C]. The 4 test regimens were 3R7 H7 Z7 E7 M7 [M3], 2R7 H7 Z7 E7 M7 /2R7 H7 M7 [M4], 2R7 H7 Z7 E7 M7 /2R3 H3 M3 [M4-I] or 2R7 H7 Z7 E7 M7 /2R3 H3 E3 M3 [M4-IE]. Treatment was directly observed. Clinical and bacteriological assessments were done monthly during treatment and for 24months post-treatment. The primary end point was TB recurrence post-treatment. Of 1371 patients, randomised, modified intention-to-treat (ITT) analysis was done in 1329 and per-protocol (PP) analysis in 1223 patients. Regimen M3 was terminated due to high TB recurrence rates. 'Favourable' response at end of treatment was 96-100% in the moxifloxacin regimensand 93% in the control regimen. Among these, the TB recurrence occurred in 4.1% in the M4 regimen and in 4.5% in the control regimen and demonstrated equivalence within a 5% margin (95% CI -3.68, 4.55). Similar findings were observed in modified ITT analysis. The TB recurrence rates in the M4-I and M4-IE regimens did not show equivalence with the control regimen. Sixteen (1.4%) of 1087 patients in the moxifloxacin regimens required treatment modification. The 4-month daily moxifloxacin regimen [M4] was found to be equivalent and as safe as the 6-month thrice-weekly control regimen.

Levels of disability and relapse in Bangladeshi MB leprosy cases, 10 years after treatment with 6m MB-MDT

Introduction: Since 1998 the recommended duration of treatment for multi- bacillary (MB) leprosy cases has been 12 months. Further shortening the duration of multi-drug therapy (MDT) for MB cases has been proposed, but evidence regarding long term outcomes is still needed. Disability outcomes are as important for the affected individual as the bacteriological response. Methods: Newly diagnosed MB leprosy cases were recruited from 2 NGO projects in Bangladesh for treatment with 6m MB-MDT, and followed up for 10 years from diagnosis. Their outcomes were compared with those in a similar annual cohort of MB cases from the same projects who were diagnosed during the previous year, treated with 12m MB-MDT, and followed up in the same way. Results: Over a 10 year period there were no differences in outcomes between the 6m MB-MDT group and the control group who received 12m MB-MDT in regard to WHO disability grade or degree of nerve function impairment (NFI). The proportion of subjects ever needing steroids for reaction/neuritis did not differ between regimens. Mean duration of steroid therapy was longer in the 12m group. Only one relapse was diagnosed in 10 years of follow-up. This occurred at 9 years follow up, from a patient in the 6m treatment group. Conclusion: In 2 cohorts of leprosy affected people who were actively followed up, the level of disability and the rate of relapse at 10 years after diagnosis was not significantly different between those receiving either 6m or 12m MB-MDT.

The use of nitrofurantoin for children with acute cystitis caused by extended-spectrum Β-lactamase–producing Escherichia coli

Acute cystitis in children caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) is on the rise. Treatment of these is usually parenteral treatment. The aim of this study was to investigate the clinical and microbiological efficacy of oral nitrofurantoin treatment in children with lower urinary tract infection (UTI) caused by ESBL-producing E. coli. Fifty children with lower UTI due to ESBL-producing E. coli were prospectively studied. Demographic data, clinical condition, laboratory values, treatment regimens, and complications of the patients were recorded. Urine samples were obtained by transurethral catheterization or clean catch; urine bags were not used for specimen collection for culture. Patients with lower UTI due to ESBL-producing E. coli and found to be susceptible to nitrofurantoin were given oral nitrofurantoin. Patients were re-evaluated 3-4 days after the end of treatment. Renal scintigraphy was performed 1-3 months after the end of treatment. A total of 50 pediatric patients (48 females and 2 males) were enrolled into study. The mean age was 7.5±3.96 years (range, 1-17 years). The duration of nitrofurantoin treatment was 10 days. Bacteriological response was observed in 49 of 50 patients (98%). No patient had symptoms after treatment. No significant side-effect was observed in any of the patients. All patients had normal serum creatinine values. Renal scintigraphic study, which was performed in all patients 1-3 months after completion of treatment, demonstrated the non-scarring in 48 of 50 patients (96%). UTIs due to ESBL-producing E. coli are a serious problem because of the bacteria's multidrug antibiotic resistance pattern. This study suggests that oral nitrofurantoin treatment could be a good alternative for lower UTI caused by ESBL-producing E. coli in pediatric patients.

Impact of Diabetes Mellitus on the Presentation and Response to Treatment of Adults With Pulmonary Tuberculosis in Qatar.

BackgroundPersons with diabetes mellitus (DM) have a 3-fold increased risk of tuberculosis (TB). Atypical radiographic findings and differences in bacteriologic response during anti-TB treatment have been reported in earlier studies; however, the findings have varied. We evaluated the effect of DM on manifestations and response to treatment in adults with pulmonary TB in Qatar.MethodsThe impact of DM on the clinical and radiographic presentations of pulmonary TB and bacteriologic response during anti-TB treatment was evaluated between January 2007 and December 2011, comparing patients with and without DM. This is a retrospective unmatched case-control study conducted at a large national hospital. Cases and controls were randomly selected from patients diagnosed with pulmonary TB over a 5-year period. Sputum culture conversion was assessed after 2 months of anti-TB treatment.ResultsClinical symptoms were similar between patients with and without DM. Patients with DM had a higher initial sputum acid-fast bacillus (AFB) smear grade and were less likely to have cavitary lesions on initial chest radiographs than patients without DM. Of 134 adults with DM and TB, 71 (53%) remained sputum culture positive after 2 months of anti-TB treatment, compared with 36 (27%) patients without DM.ConclusionsDM was associated with atypical radiographic findings and delayed sputum culture conversion at 2 months in adults with pulmonary TB in Qatar. Increased health education of patients with DM about symptoms of TB, low thresholds for evaluation for active TB, and close monitoring of bacteriologic response to treatment among patients with TB and DM are warranted.

Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women

The use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection (UTI). To compare the clinical and microbiologic efficacy of nitrofurantoin and fosfomycin in women with uncomplicated cystitis. Multinational, open-label, analyst-blinded, randomized clinical trial including 513 nonpregnant women aged 18 years and older with symptoms of lower UTI (dysuria, urgency, frequency, or suprapubic tenderness), a positive urine dipstick result (with detection of nitrites or leukocyte esterase), and no known colonization or previous infection with uropathogens resistant to the study antibiotics. Recruitment took place from October 2013 through April 2017 at hospital units and outpatient clinics in Geneva, Switzerland; Lodz, Poland; and Petah-Tiqva, Israel. Participants were randomized in a 1:1 ratio to oral nitrofurantoin, 100 mg 3 times a day for 5 days (n = 255), or a single 3-g dose of oral fosfomycin (n = 258). They returned 14 and 28 days after therapy completion for clinical evaluation and urine culture collection. The primary outcome was clinical response in the 28 days following therapy completion, defined as clinical resolution (complete resolution of symptoms and signs of UTI without prior failure), failure (need for additional or change in antibiotic treatment due to UTI or discontinuation due to lack of efficacy), or indeterminate (persistence of symptoms without objective evidence of infection). Secondary outcomes included bacteriologic response and incidence of adverse events. Among 513 patients who were randomized (median age, 44 years [interquartile range, 31-64]), 475 (93%) completed the trial and 377 (73%) had a confirmed positive baseline culture. Clinical resolution through day 28 was achieved in 171 of 244 patients (70%) receiving nitrofurantoin vs 139 of 241 patients (58%) receiving fosfomycin (difference, 12% [95% CI, 4%-21%]; P = .004). Microbiologic resolution occurred in 129 of 175 (74%) vs 103 of 163 (63%), respectively (difference, 11% [95% CI, 1%-20%]; P = .04). Adverse events were few and primarily gastrointestinal; the most common were nausea and diarrhea (7/248 [3%] and 3/248 [1%] in the nitrofurantoin group vs 5/247 [2%] and 5/247 [1%] in the fosfomycin group, respectively). Among women with uncomplicated UTI, 5-day nitrofurantoin, compared with single-dose fosfomycin, resulted in a significantly greater likelihood of clinical and microbiologic resolution at 28 days after therapy completion. ClinicalTrials.gov Identifier: NCT01966653.

The Relationship Between Vancomycin Trough Concentrations and AUC/MIC Ratios in Pediatric Patients: A Qualitative Systematic Review.

In adults, the area under the concentration-time curve (AUC) divided by the minimum inhibitory concentration (MIC) is associated with better clinical and bacteriological response to vancomycin in patients with methicillin-resistant Staphylococcus aureus who achieve target AUC/MIC≥400. This target is often extrapolated to pediatric patients despite the lack of similar evidence. The impracticalities of calculating the AUC in practice means vancomycin trough concentrations are used to predict the AUC/MIC. This review aimed to determine the relationship between vancomycin trough concentrations and AUC/MIC in pediatric patients. We searched the MEDLINE and Embase databases, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials using the medical subject heading (MeSH) terms vancomycin and AUC and pediatric* or paediatric*. Articles were included if they were published in English and reported a relationship between vancomycin trough concentrations and AUC/MIC. Of 122 articles retrieved, 11 met the inclusion criteria. One trial reported a relationship between vancomycin trough concentrations, AUC/MIC, and clinical outcomes but was likely underpowered. Five studies found troughs 6-10mg/l were sufficient to attain an AUC/MIC>400 in most general hospitalized pediatric patients. One study in patients undergoing cardiothoracic surgery found a trough of 18.4mg/l achieved an AUC/MIC>400. Two oncology studies reported troughs≥15mg/l likely attained an AUC/MIC≥400. In critical care patients:one study found a trough of 9mg/l did not attain the AUC/MIC target; another found 7mg/l corresponded to an AUC/MIC of 400. Potential vancomycin targets varied based on the population studied but, for general hospitalized pediatric patients, troughs of 6-10mg/l are likely sufficient to achieve AUC/MIC≥400. For MIC≥2mg/l, higher troughs are likely necessary to achieve an AUC/MIC≥400. More research is needed to determine the relationships between vancomycin trough concentrations, AUC/MIC, and clinical outcomes.

Treatment of Diabetic Foot Infections: A Prospective Study Highlighting the Efficacy and Safety of Moxifloxacin

Background: Foot infection involving the skin, soft tissues and bony structures, is a common complication of foot ulcers in diabetic individuals and represents a major cause of morbidity and mortality. Systemic antibiotic treatment must be given as early as possible initially on empirical basis and based on the response to empirical therapy and wound culture and sensitivity results, definitive therapy should be decided. This study was conducted to assess the efficacy and safety of moxifloxacin for treating diabetic foot infections in Pakistani population. Methods: After taking ethical approval, an interventional phase IV study was conducted in the department of medicine and diabetic clinic, Liaquat University Hospital, Jamshoro, Hyderabad from March 2017 till August 2017. A total of 75 patients with diabetic foot infection who were sensitive to moxifloxacin on culture and sensitivity were included in the study using non-probability convenient sampling technique. All the demographic and clinical information was collected by using a questionnaire specially designed for the study. After making clinical assessment, all the patients were treated with sequential intravenous/oral moxifloxacin for 14 days. Bacteriologic response was based on the results of cultures of specimens of infected skin or soft tissue or blood. The data were analyzed on SPSS version 20.0. Chi-square test was used with significant level set at 0.05. Results: The study results revealed that the majority of patients with diabetic foot ulcer were males with the age of greater than 45 years. Only 21.3% of them had a comorbidity, either hypertension alone or hypertension with ischemic heart disease, whereas 84% of them reported their foot ulcers to be cured at the end of treatment. Furthermore, only younger age was found to have a significant positive association with healing of foot ulcers. Conclusions: Moxifloxacin is effective in treating diabetic foot infections and 84% of the diabetic patients in the present study reported the healing of foot ulcers as a result of a 2-week moxifloxacin treatment. Further evaluation of the role of moxifloxacin in the treatment of diabetic foot ulcer is recommended. J Endocrinol Metab. 2018;8(2-3):32-36 doi: https://doi.org/10.14740/jem485w