Duration Of Antimicrobial Therapy Research Articles

Prescription Pattern of Antibiotics in Paediatric Patients in a Rural Teaching Hospital of North India

Introduction: Due to complex dosage calculations, requirement and different pharmacokinetics profile of drugs in paediatric population, there is a risk of development of drug resistance due to the excessive and inappropriate use of antibiotics. The aim of this study is to determine the antibiotic prescriptions pattern and analyse the rationale use of antibiotic in paediatric patient. Methods: A prospective observational study was carried out for the period of six months. Data was obtained from the records of paediatric patients between six months to 12 years of age who visited the hospital for febrile illnesses. Appropriateness of the prescriptions was evaluated by considering various parameters like selection of antibiotics (adherence to standard treatment protocols of childhood febrile illnesses), dose, dosage form, route, frequency and duration of antibiotic administration. Quantitative data was analysed in terms of percentage and graphs. Results: One hundred and fifty prescriptions in a successive manner from paediatric department were collected and analysed, out of which 40% were male & 60% were female cases. The mean age of the patients was 5.9 ± 3.3 years. The range of duration of antimicrobial therapy was 3 - 9 days (6.03 ± 3.53 days). Sixty six percent of paediatric patients were on single antibiotic and most of the paediatric patients were receiving parenteral preparation. The antibiotic treatment was given on the basis of definitive diagnosis in 52% and empirical therapy in 46% cases. Antibiotic prescribed were from class cephalosporin (80%) followed by penicillin (18%) and microcline (14%), glycopeptides (2%) and nitroimidazoles (2%). Conclusions: Febrile children received antibiotics on an empirical basis, in accordance with standard treatment protocols. Cephalosporins are the major class of drugs prescribed.

Comparison of Short- versus Long-Course Antimicrobial Therapy of Uncomplicated Bacterial Pneumonia in Dogs: A Double-Blinded, Placebo-Controlled Pilot Study.

Simple SummaryDogs diagnosed with bacterial pneumonia are often treated with long courses of antibiotics (3–6 weeks) and chest X-rays are used to help guide the duration of treatment. This is in stark contrast with humans with the same disease who are often treated for 5–10 days, and chest X-rays are not considered to be useful for monitoring response to treatment. The main goal of this study was to determine whether a shorter course of antibiotics (10 days) would be sufficient to treat dogs with bacterial pneumonia. Eight dogs with pneumonia were randomly assigned to receive 10 or 21 days of antibiotics. They were evaluated at 10, 30 and 60 days after diagnosis. At 10 days, 6/8 dogs had resolution of both clinical signs and evidence of inflammation on bloodwork and 5/8 dogs showed improvement in the chest X-rays. After 60 days, none of the dogs had clinical signs or evidence of inflammation on bloodwork regardless of antibiotic therapy duration. However, 3/8 dogs showed changes in the chest X-rays. This study suggests that a 10-day course of antibiotics may be sufficient to treat dogs with bacterial pneumonia, and chest X-rays may not be a reliable marker to monitor response to therapy.Current treatment for canine bacterial pneumonia relies on protracted courses of antimicrobials (3–6 weeks or more) with recommendations to continue for 1–2 weeks past resolution of all clinical and thoracic radiographic abnormalities. However, in humans, bacterial pneumonia is often treated with 5–10-day courses of antimicrobials, and thoracic radiographs are not considered useful to guide therapeutic duration. The primary study objective was to determine whether a short course of antimicrobials would be sufficient to treat canine bacterial pneumonia. Eight dogs with uncomplicated bacterial pneumonia were enrolled in this randomized, double-blinded, placebo-controlled study comparing clinical and radiographic resolution with differing durations of antimicrobial therapy. Dogs received a course of antimicrobials lasting 10 (A10) or 21 (A21) days. Dogs randomized to the A10 group received placebo for 11 days following antimicrobial therapy. Patients were evaluated at presentation and 10, 30 and 60 days after the initiation of antimicrobials. At 10 days, 6/8 dogs had resolution of both clinical signs and inflammatory leukogram, and 5/8 dogs had improved global radiographic scores. After 60 days, clinical and hematologic resolution of pneumonia was noted in all dogs regardless of antimicrobial therapy duration; however, 3/8 dogs had persistent radiographic lesions. Thoracic radiographs do not appear to be a reliable marker to guide antimicrobial therapy in canine bacterial pneumonia as radiographic lesions may lag or persist despite clinical cure. This pilot study suggests a 10-day course of antimicrobials may be sufficient to treat uncomplicated canine bacterial pneumonia.

Optimization of sepsis therapy based on patient-specific digital precision diagnostics using next generation sequencing (DigiSep-Trial)\u2014study protocol for a randomized, controlled, interventional, open-label, multicenter trial

BackgroundSepsis is triggered by an infection and represents one of the greatest challenges of modern intensive care medicine. With regard to a targeted antimicrobial treatment strategy, the earliest possible pathogen detection is of crucial importance. Until now, culture-based detection methods represent the diagnostic gold standard, although they are characterized by numerous limitations. Culture-independent molecular diagnostic procedures represent a promising alternative. In particular, the plasmatic detection of circulating, cell-free DNA by next-generation sequencing (NGS) has shown to be suitable for identifying disease-causing pathogens in patients with bloodstream infections.MethodsThe DigiSep-Trial is a randomized, controlled, interventional, open-label, multicenter trial characterizing the effect of the combination of NGS-based digital precision diagnostics with standard-of-care microbiological analyses compared to solely standard-of-care microbiological analyses in the clinical picture of sepsis/septic shock. Additional anti-infective expert consultations are provided for both study groups. In 410 patients (n = 205 per arm) with sepsis/septic shock, the study examines whether the so-called DOOR-RADAR (Desirability of Outcome Ranking/Response Adjusted for Duration of Antibiotic Risk) score (representing a combined endpoint including the criteria (1) intensive/intermediate care unit length of stay, (2) consumption of antibiotics, (3) mortality, and (4) acute kidney injury (AKI)) can be improved by an additional NGS-based diagnostic concept. We also aim to investigate the cost-effectiveness of this new diagnostic procedure. It is postulated that intensive/intermediate care unit length of stay, mortality rate, incidence of AKI, the duration of antimicrobial therapy as well as the costs caused by complications and outpatient aftercare can be reduced. Moreover, a significant improvement in patient’s quality of life is expected.DiscussionThe authors´ previous work suggests that NGS-based diagnostics have a higher specificity and sensitivity compared to standard-of-care microbiological analyses for detecting bloodstream infections. In combination with the here presented DigiSep-Trial, this work provides the optimal basis to establish a new NGS-driven concept as part of the national standard based on the best possible evidence.Trial registrationsDRKS-ID DRKS00022782. Registered on August 25, 2020ClinicalTrials.govNCT04571801. Registered October 1, 2020

349 Utilization of an Antibiogram and a Pathway for Urinary Tract Infections in a Pediatric Emergency Department to Improve Empiric Antimicrobial Treatment: A Quality Improvement Project

Escherichia coli is the most common cause of pediatric urinary tract infections (UTI). Antimicrobial resistance including extended spectrum beta-lactamase (ESBL) has increased alarmingly since the early 2000s, leaving antibiotics such as penicillins and cephalosporins ineffective. Overutilization of third generation cephalosporins (3GC) can add selective pressure and serve as a risk factor for development of an ESBL infection. An antibiotic review at our institution demonstrated children with community-acquired UTIs were receiving a 3GC as a part of treatment from the emergency department (ED). A UTI-specific antibiogram demonstrated good susceptibility to first generation cephalosporins (1GC). Our primary objective was to provide education based on our antibiogram and implement a UTI pathway in the ED to decrease the overall use of 3GC while maintaining clinical outcomes. This was a prospective study in a freestanding urban academic pediatric medical system consisting of an ED with an annual census of 60, 000 patients (Site A) as well as a small satellite non-academic campus ED (Site B). Data was collected from July 2019 to June 2020 and included patients 60 days to 18 years of age with a positive urine culture and a diagnosis of UTI who were discharged from the ED, excluding those with concurrent urologic conditions and non-UTI infections. Data was collected pre-implementation (July 2019 - October 2019) and post-implementation (December 2019 - June 2020) of our interventions at Site A. (See Figure 1) Interventions included provider huddles, education, and pathway implementation. Site B acted as a control group where the pathway was available but the education and provider huddles were not implemented. The primary outcome was comparing the frequency that the proposed empiric treatment pathway was followed pre- and post-interventions, and was analyzed using the Binomial Test. The secondary outcome was comparing the antibiotic treatment days, and was analyzed using the Mann-Whitney U Test. 309 pediatric patient encounters (194 from Site A and 115 from Site B) were included; 122 pre- and 187 post-intervention. 286 (93%) were female, and 139 (45%) were Caucasian. Mean age (years) was 6.86 (range 0.2-18). 271 (87%) urine cultures grew E. coli. Of all gram-negative pathogens isolated, 88% were susceptible to 1GC. For Site A, the correct drug based on pathway was improved from 36% to 69.2% post-intervention (p = <0.001) with a median of 81%. Median duration of antimicrobial therapy at Site A pre-intervention was 11 days and post-intervention was 10 days (p = 0.004). Site B showed no change in correct drug or duration. The most common initial antibiotic prescribed at Site A was 3GC (59%) pre-intervention and 1GC (60%) post-intervention. 3GC was most common at Site B both pre- (72%) and post-intervention (55%). Our data demonstrates that a pathway alone will not change practice. Education at different levels (attendings and trainees) and provider huddles along with a pathway improved antimicrobial prescribing patterns in pediatric patients with a community-acquired UTI. Overall, this study is generalizable to other populations and will be expanded to include other clinical settings in an effort to continue improving antimicrobial usage in children.

Short versus prolonged courses of antimicrobial therapy for patients with uncomplicated Pseudomonas aeruginosa bloodstream infection: a retrospective study.

The optimal duration of antimicrobial therapy for uncomplicated Pseudomonas aeruginosa bloodstream infection (BSI) is unknown. We compared the outcomes of short and prolonged courses of antimicrobial therapy in adults with uncomplicated pseudomonal BSI. All patients with uncomplicated P. aeruginosa BSI admitted at a tertiary-care hospital from April 2010 to April 2020 were included. We compared the primary outcome (a composite of the rate of recurrent P. aeruginosa infection and mortality within 30 days after discontinuing antimicrobial therapy) among patients who underwent short (7‒11 days) and prolonged (12‒21 days) courses of antimicrobial therapy using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. We evaluated 1477 patients with P. aeruginosa BSI; of them, 290 met the eligibility criteria who received antimicrobial agents with in vitro activity, including 97 (33%) who underwent short-course therapy [median of 9 (IQR = 8‒11) days] and 193 (67%) who underwent prolonged-course therapy [median of 15 (IQR = 14‒18) days]. We found no significant difference in the risk of recurrence or 30 day mortality between the prolonged-course and short-course groups [n = 30 (16%) versus n = 11 (11%); IPTW-adjusted HR = 0.68, 95% CI = 0.34 - 1.36, P = 0.28]. The prolonged-course therapy did not significantly reduce the risk of the recurrence of P. aeruginosa infection within 180 days compared with short-course therapy [n = 37 (19%) versus n = 12 (12%); IPTW-adjusted HR = 0.57, 95% CI = 0.29 - 1.10, P = 0.09]. Short-course antimicrobial therapy could be as effective as prolonged-course therapy for uncomplicated P. aeruginosa BSI.

La polmonite acquisita in comunità

Community-acquired pneumonia (CAP) is one of the most common serious infections in children. The appropriate duration of antimicrobial therapy is unclear. In current practice antibiotic treatment courses of 10 days are prescribed in mild-moderate CAP, while up to 14-21-day courses in severe and complicated cases. The results of the SAFER (Short-Course Antimicrobial Therapy for Paediatric Respiratory Infections) study found that the “short therapy” appeared to be comparable to standard care for the treatment of previously healthy children with CAP not requiring hospitalization. Clinical practice guidelines should recommend 5 days of amoxicillin for paediatric pneumonia management in accordance with antimicrobial stewardship principles.

How Antibiotics Stewardship Can Be Safely Implemented in Patients with Septic Shock?

In critically ill patients with sepsis and septic shock, the need for prompt and adequate antibiotic therapy is balanced by the risk of excessive antibiotic exposure that leads to emergence of multidrug-resistant pathogens. As such, antibiotic stewardship programs propose a set of operating rules from antibiotic treatment initiation to de-escalation and finally cessation. In this review, we will describe the rationale for early antibiotic treatment in septic patients, how to optimize initial antibiotic treatment, rules for early treatment discontinuation in pathogen-negative sepsis, and optimal duration of antimicrobial therapy.

Open Fractures - What Is the Evidence, and How Can We Improve?

Open fractures can have devastating consequences, including chronic infections and amputations, leaving patients with life-changing disabilities. Prompt and appropriate treatment can spare patients the sequelae of open fractures and the long-term economic burden these injuries often inflict. The British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST-4) guideline outlines the acute management of patients with open fractures and is often considered the gold standard for open fracture management in the UK. In an era of evidence-based medicine, clinicians are continually mindful of the science behind current guidelines and practices. This article aims to critique the evidence underpinning the BOAST-4 guidelines and suggest improvements based on contemporary literature. Antibiotic delivery in the prehospital setting, the type and duration of antimicrobial therapy, timing for the conversion from external to internal fixation, and the differentiation between adult and paediatric open fractures were among the many pertinent topics critiqued, and evidence-based improvements suggested.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Current opinion in management of septic shock due to Gram-negative bacteria.

The COVID-19 pandemic has caused multiple challenges to ICUs, including an increased rate of secondary infections, mostly caused by Gram-negative micro-organisms. Worrying trends of resistance acquisition complicate this picture. We provide a review of the latest evidence to guide management of patients with septic shock because of Gram-negative bacteria. New laboratory techniques to detect pathogens and specific resistance patterns from the initial culture are available. Those may assist decreasing the time to adequate antimicrobial therapy and avoid unnecessary broad-spectrum antibiotic overuse. New antimicrobials, including β-lactam/β-lactamase inhibitor combinations, such as ceftolozane-tazobactam, imipenem-relebactam or meropenem-vaborbactam and cephalosporins, such as cefiderocol targeted to specific pathogens and resistance patterns are available for use in the clinical setting. Optimization of antibiotic dosing and delivery should follow pharmacokinetic and pharmacodynamic principles and wherever available therapeutic drug monitoring. Management of sepsis has brought capillary refill time back to the spotlight along with more reasoned fluid resuscitation and a moderate approach to timing of dialysis initiation. Novel rapid diagnostic tests and antimicrobials specifically targeted to Gram-negative pathogens are available and should be used within the principles of antimicrobial stewardship including de-escalation and short duration of antimicrobial therapy.

Compliance with the 4Ds of antimicrobial stewardship practice in a tertiary care centre.

BackgroundAntimicrobial stewardship describes the practice of promoting the selection of the right drug, dosage, delivery and duration of antimicrobial therapy (the 4Ds) in order to curtail the emergence of resistant organisms. It is important to quantify the inappropriate use of antimicrobials in terms of percentage adherence to each of the 4Ds mentioned.MethodsWe undertook a prospective review of medical records of patients admitted to the medical wards of a tertiary care centre in North India. All patients on antimicrobials were included and their records reviewed for indication, drug, dose, delivery and duration (or by asking the treating physician if not documented). Adherence to the 4Ds was determined by referring to updated literature-based standard treatment guidelines (STGs) for each specific disease.ResultsOf 304 patients, drugs were appropriate and matched STGs in 218 (72%) patients, with adherence to the right dose in 210 (69%), route of delivery in 216 (71%) and duration in 197 (65%). Full adherence to the 4Ds was observed in 196 (64.5%). Maximum adherence was observed in treating skin and soft tissue infections (100%), while minimum adherence was observed in administering medical prophylaxis (40%). WHO Access, Watch and Reserve categories comprised 29%, 63% and 8.5% of all prescribed antibiotics, respectively.ConclusionsThe right drug, dose, delivery and duration of therapy are prescribed in 72%, 69%, 71%, and 65% of patients, respectively. In order to increase the adherence to 100%, bedside stewardship practices in the form of prospective audits and feedback must be improved. There is a need to integrate WHO AWaRe classification of antibiotics into treatment guidelines.

Early antimicrobial stewardship team intervention on appropriateness of antimicrobial therapy in suspected sepsis: a randomized controlled trial.

ObjectivesThere has been concern that the imperative to administer rapid antimicrobials in septic patients may result in inappropriate antimicrobial use. We aimed to determine the impact of early antimicrobial stewardship (AMS) team intervention in patients with Medical Emergency Team (MET) calls for suspected sepsis.MethodsWe performed a randomized controlled trial of non-ICU inpatients who had a MET call for suspected sepsis. Patients were randomized to standard care (management of antimicrobial therapy by the treating team) or early targeted intervention (AMS review 48 h post-MET call). The primary outcome was appropriateness of antimicrobial therapy 72 h post-MET call, as determined by a panel of blinded infectious diseases physicians.ResultsIn total, 90 patients were enrolled; 45 were randomly allocated to the intervention group, and 45 to the control group. More patients in the AMS intervention group were receiving appropriate antimicrobials 72 h following the MET call (67% versus 44%, P = 0.03). In the intervention group, 27 recommendations were made by the AMS team; 74% of recommendations were accepted, including 30% of cases where antimicrobials were discontinued or de-escalated. There were non-significant differences in total duration of antimicrobial therapy (8.7 versus 10.7 days, P = 0.39), sepsis-related ICU-admission rates (13% versus 18%, P = 0.56) and sepsis-related in-hospital mortality (7% versus 9%, P = 0.71) between intervention and control groups, respectively.ConclusionsAMS team intervention resulted in significant improvement in appropriateness of antimicrobial therapy following MET calls due to suspected sepsis. Targeted AMS review should be implemented to support early antimicrobial de-escalation and optimization in patients with suspected sepsis.

Nonalcoholic Fatty Liver Disease-A Novel Risk Factor for Recurrent Clostridioides difficile Infection.

Recurrent Clostridioides difficile infections (rCDI) have a substantial impact on healthcare systems, with limited and often expensive therapeutic options. Nonalcoholic fatty liver disease (NAFLD) affects about 25% of the adult population and is associated with metabolic syndrome, changes in gut microbiome and bile acids biosynthesis, all possibly related with rCDI. The aim of this study was to determine whether NAFLD is a risk factor associated with rCDI. A retrospective cohort study included patients ≥ 60 years hospitalized with CDI. The cohort was divided into two groups: those who were and were not readmitted with CDI within 3 months of discharge. Of the 329 patients included, 107 patients (32.5%) experienced rCDI. Patients with rCDI were older, had higher Charlson Age–Comorbidity Index (CACI) and were more frequently hospitalized within 3 months. Except for chronic kidney disease and NAFLD, which were more frequent in the rCDI group, there were no differences in other comorbidities, antibiotic classes used and duration of antimicrobial therapy. Multivariable Cox regression analysis showed that age >75 years, NAFLD, CACI >6, chronic kidney disease, statins and immobility were associated with rCDI. In conclusion, our study identified NAFLD as a possible new host-related risk factor associated with rCDI.

A Physician-Driven Quality Improvement Stewardship Intervention Using Lean Six Sigma Improves Patient Care for Community-Acquired Pneumonia.

The Infectious Diseases Society of America (IDSA) recommends a minimum of 5 days of antibiotic therapy in stable patients who have community-acquired pneumonia (CAP). However, excessive duration of therapy (DOT) is common. Define, measure, analyze, improve, and control (DMAIC) is a Lean Six Sigma methodology used in quality improvement efforts, including infection control; however, the utility of this approach for antimicrobial stewardship initiatives is unknown. To determine the impact of a prospective physician-driven stewardship intervention on excess antibiotic DOT and clinical outcomes of patients hospitalized with CAP. Our specific aim was to reduce excess DOT and to determine why some providers treat beyond the IDSA minimum DOT. A single-center, quasi-experimental quality improvement study evaluating rates of excess antimicrobial DOT before and after implementing a DMAIC-based antimicrobial stewardship intervention that included education, prospective audit, and feedback from a physician peer, and daily tracking of excess DOT on a Kaizen board. The baseline period included retrospective CAP cases that occurred between October 2018 and February 2019 (control group). The intervention period included CAP cases between October 2019 and February 2020 (intervention group). A total of 123 CAP patients were included (57 control and 66 intervention). Median antibiotic DOT per patient decreased (8 versus 5 days; p < 0.001), and the proportion of patients treated for the IDSA minimum increased (5.3% versus 56%; p < 0.001) after the intervention. No differences in mortality, readmission, length of stay, or incidence of Clostridioides difficile infection were observed between groups. Almost half of the caregivers surveyed were aware that as few as 5 days of antibiotic treatment could be appropriate. A physician-driven antimicrobial quality improvement initiative designed using DMAIC methodology led to reduced DOT and increased compliance with the IDSA treatment guidelines for hospitalized patients with CAP reduced without negatively affecting clinical outcomes.

Clinical features of bacterial meningitis among hospitalised children in Kenya

BackgroundDiagnosing bacterial meningitis is essential to optimise the type and duration of antimicrobial therapy to limit mortality and sequelae. In sub-Saharan Africa, many public hospitals lack laboratory capacity, relying on clinical features to empirically treat or not treat meningitis. We investigated whether clinical features of bacterial meningitis identified prior to the introduction of conjugate vaccines still discriminate meningitis in children aged ≥60 days.MethodsWe conducted a retrospective cohort study to validate seven clinical features identified in 2002 (KCH-2002): bulging fontanel, neck stiffness, cyanosis, seizures outside the febrile convulsion age range, focal seizures, impaired consciousness, or fever without malaria parasitaemia and Integrated Management of Childhood Illness (IMCI) signs: neck stiffness, lethargy, impaired consciousness or seizures, and assessed at admission in discriminating bacterial meningitis after the introduction of conjugate vaccines. Children aged ≥60 days hospitalised between 2012 and 2016 at Kilifi County Hospital were included in this analysis. Meningitis was defined as positive cerebrospinal fluid (CSF) culture, organism observed on CSF microscopy, positive CSF antigen test, leukocytes ≥50/μL, or CSF to blood glucose ratio <0.1.ResultsAmong 12,837 admissions, 98 (0.8%) had meningitis. The presence of KCH-2002 signs had a sensitivity of 86% (95% CI 77–92) and specificity of 38% (95% CI 37–38). Exclusion of ‘fever without malaria parasitaemia’ reduced sensitivity to 58% (95% CI 48–68) and increased specificity to 80% (95% CI 79–80). IMCI signs had a sensitivity of 80% (95% CI 70–87) and specificity of 62% (95% CI 61–63).ConclusionsA lower prevalence of bacterial meningitis and less typical signs than in 2002 meant the lower performance of KCH-2002 signs. Clinicians and policymakers should be aware of the number of lumbar punctures (LPs) or empirical treatments needed for each case of meningitis. Establishing basic capacity for CSF analysis is essential to exclude bacterial meningitis in children with potential signs.

Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection

BackgroundThe management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear.MethodsWe performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points.ResultsA total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events.ConclusionsAmong patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.)

Efficacy and safety of probiotics and prebiotics in liver transplantation: A systematic review and meta-analysis.

Probiotics were used for liver transplantation (LT) patients to reduce postoperative infection, but clinical trials examining the combined use of prebiotics and probiotics are limited. This meta-analysis aimed to compare the safety and efficacy of combined use of prebiotics and probiotics in patients undergoing LT. PubMed, Cochrane, and Embase databases were reviewed for the combined use of prebiotics and probiotics in patients undergoing LT. The weighted mean difference (WMD), risk ratio (RR), and 95% CI were calculated. A total of 6 related studies comprising 345 patients were included. Most prebiotics and probiotics were given for 7.14 days. The overall infection rate (RR = 0.29; 95% CI, 0.14.0.60; P value for heterogeneity [PH ] = .066; test for heterogeneity [I2 ] = 51.7%) and the incidence of urinary tract infection (RR = 0.14; 95% CI, 0.04-0.47, PH = .724; I2 = 0%) were lower in the probiotics group when compared with those in the control group. Furthermore, probiotics significantly reduced the hospital length of stay (WMD = -1.37; 95% CI, -1.92 to 0.82; PH = .506; I2 = 0%) and the duration of antimicrobial therapy (WMD = -4.31; 95% CI, -5.41 to 3.22; PH = .019; I2 = 69.8%) in patients undergoing LT. These findings suggested that the combined use of prebiotics and probiotics (Lactobacillus and Bifidobacterium) was effective in lowering the incidence of bacterial infections and shortening the hospital length of stay and duration of antibiotic therapy in patients undergoing LT, when compared with conventional nutrition.

Impact of Prophylactic Ureaplasma-Directed Antimicrobials in Lung Donors

<h3>Purpose</h3> Hyperammonemia syndrome (HS) is a fatal complication, refractory to medical treatment, which can affect over 5% of lung transplant as well as other solid organ recipients. We recently discovered that a Mollicute, Ureaplasma spp, leads to the development of HS. Subsequently, in a prospective study, we found a high incidence of Ureaplasma in the donor lungs which is associated with serious post-transplant complications. Here, we evaluated the impact of prophylactic Ureaplasma treatment for lung donors. <h3>Methods</h3> A single institution lung transplant study with consecutive patients with lung transplant from 2014 through 2020. We included consecutive patients from January 2014 through August 2020, and total 13 patients were included. Lung donors were treated prophylactically using a dual antimicrobial agent with a fluoroquinolone (levofloxacin 500mg q12h) and azithromycin (500mg IV q24h) after Septembver 2017. <h3>Results</h3> While two patients died of HS prior to the initiation of Ureaplasma prophylaxis, there were no new cases of HS in 92 consecutive patients (6.8% vs 0% respectively, p=0.01) subsequently (Table 1). Additionally, following initiation of Ureaplasma prophylaxis, the incidence of Ureaplasma infection in donor lungs reduced from 27.5% to 9.7% (p=0.01). The median duration of antimicrobial therapy in the donor was 1.7 days. <h3>Conclusion</h3> Given the high rates of Ureaplasma infection approaching 30% in the donor lungs, as well as the morbidity and mortality associated with recipient Ureaplasma infection, we propose that donor lungs be screened prior to implantation. However, when that is not feasible, the short duration of Ureaplasma prophylaxis is a safe and highly effective alternative to completely prevent the fatal hyperammonemia syndrome.

Bovhyaluronidaze azoximer as an antimicrobial alternative in companion animals

Antimicrobial resistance formation in various bacteria is a serious biosafety threat. In this regard, the important issue in medical and veterinary fields is not only the rational use of antibacterial drugs, but also the search for ways to significantly reduce the need for antibiotics. Three studies designed to research into these challenges are described. The results indicated that (1) the bacteriuria presences in 62.4 +/- 4.1% of urine samples obtained from companion animals (the microflora count in urine samples is estimated from ‘++’ to ‘Entire Field-of-View’); (2) 16.3 +/- 4.0% of samples from companion animals showed bacteria with low antibiotics sensitivity, and 8.1 +/- 3.0% of samples contained bacteria resistant to 30 antibiotics included in the susceptibility test; (3) the Bovhyaluronidaze azoximer reduce antimicrobial therapy duration statistically significant (p=0.0089). The studies were conducted at the facilities of St. Petersburg State University of Veterinary Medicine and Bars veterinary clinic chain in St. Petersburg, Russia. A randomized clinical trial of Bovhyaluronidaze azoximer effect on course of disease and treatment duration of acute and chronic prostatitis and urocystitis, including complicated by urolithiasis, was conducted in 54 animals. Animals were randomly assigned to intervention (n=34) and control (n=20) groups. The animals of both groups received the antimicrobial therapy. Interventional group patients additionally received Bovhyaluronidaze azoximer in the form of rectal suppositories. The antimicrobial therapy mean duration in intervention group animals took 14.88 +/- 4.98 days, in control group animals — 18.65 +/- 5.40 days. The study findings imply that bacteriuria is widely prevalent in companion animals and antimicrobial resistance is increasing issue in veterinary medicine. Bovhyaluronidaze azoximer contributes to microcirculation restore and increases the bioavailability of antibacterial drugs at the site of infection. This makes its relevant for use in the complex treatment for septic and inflammatory processes. This allows to reduce the antimicrobial course duration (and completely decline antibiotic therapy in some cases) and prevent the formation of chronic inflammation and infection sites.

Bloodstream Infections Caused by Carbapenem-Resistant Enterobacterales: Risk Factors for Mortality, Antimicrobial Therapy and Treatment Outcomes from a Prospective Multicenter Study.

PurposeCarbapenem-resistant Enterobacterales bloodstream infections (CRE BSIs) have a high mortality. However, an optimal antimicrobial treatment has not been determined. This study was conducted to evaluate the risk factors for mortality and provided potential therapeutic options for treatment of CRE infection.Patients and MethodsWe investigated patients with CRE BSIs from 18 hospitals across nine Chinese provinces from January to December 2019. Data were collected from the medical records according to a pre-established questionnaire. Antimicrobial susceptibility testing and DNA sequencing were performed to investigate the characteristics of isolates.ResultsA total of 208 patients enrolled; the overall 30-day mortality rate was 46.2%. The causative pathogen was carbapenem-resistant Klebsiella pneumoniae (CRKP) (85.6%). Patients infected by ST11-KL64 CRKP had a high sepsis/septic shock incidence rate (p < 0.05). Sepsis/septic shock, short duration of antimicrobial therapy and empirical using tigecycline were independent risk factors for mortality (p < 0.05 for each risks). Appropriate therapy had better survival benefit than inappropriate therapy (p = 0.003). No difference was identified between monotherapy and combination therapy (p = 0.105). Tigecycline as a frequently used antimicrobial had poor therapeutic effect on BSI patients (p < 0.001). Carbapenem-based treatment had a better therapeutic effect on patients infected by isolates with meropenem MIC ≤ 8 mg/L (p = 0.022). The patients who received short duration of antimicrobial therapy had poorer prognosis (p < 0.001) than the patients who received long duration of antimicrobial therapy.ConclusionReducing the mortality of CRE BSIs need to comprehensively consider whether the antimicrobials were used appropriately, together with infection severity and CRE strains.