Antibiotic-related Side Effects Research Articles

Quantification of cefuroxime and flucloxacillin in synovial tissue and bone using ultra-performance convergence chromatography-tandem mass spectrometry

After a revision surgery, approximately 1–2 % of patients will develop a periprosthetic joint infection (PJI). During the revision surgery, the infected prosthesis is removed, a debridement is performed and a new or temporary spacer is placed. Additionally, patients are treated with antibiotics during and after the surgery. Adequate exposure of the administered antibiotic to the pathogen is of crucial importance during the treatment of any infection. Inadequately low concentrations are associated with an increase in antibiotic resistance, antibiotic related side effects, treatment failures and prolonged infections. While high concentrations may lead to serious adverse events and potential lasting damage. Despite the importance of optimal dosing, there is a lack of knowledge with respect to the correlation between the plasma concentrations and target site concentrations of the antibiotics. Two of the commonly administered antimicrobial agents during the arthroplasty exchange are cefuroxime and flucloxacillin. Therefore, an accurate, specific, and sensitive quantification method is required in order to assess pharmacokinetics of cefuroxime and flucloxacillin in synovial tissue and bone. The aim of this study is to develop and validate a quantification method for the measurement of cefuroxime and flucloxacillin in human synovial tissue and bone using the UPC2-MS/MS conform Food and Drug Administration guidelines. The method was found linear for both compounds in both matrices (r2 > 0.990) from 1 µg/g to 20 µg/g, except for cefuroxime in bone, which was validated from 1 µg/g to 15 µg/g. We developed and validated a quantification method for cefuroxime and flucloxacillin in synovial tissue and bone using a simple sample preparation and a short analysis run time of 5.0 min, which has been already successfully applied in a clinical study. To our knowledge, no methods have been described earlier for the simultaneous quantification of cefuroxime and flucloxacillin in synovial tissue and bone.

Is antibiotic prophylaxis generally safe and effective in surgical and nonsurgical scenarios? Evidence from an umbrella review of randomized controlled trials.

The authors aimed to comprehensively evaluate the efficacy and safety of antibiotic prophylaxis through surgical and nonsurgical scenarios and assess the strength of evidence. The authors performed an umbrella review of meta-analyses of randomized controlled trials (RCTs). An evidence map was created to summarize the absolute benefits of antibiotic prophylaxis in each scenario and certainty of evidence. Seventy-five meta-analyses proved eligible with 725 RCTs and 78 clinical scenarios in surgical and medical prophylaxis. Of 119 health outcomes, 67 (56.3%) showed statistically significant benefits, 34 of which were supported by convincing or highly suggestive evidence from RCTs. For surgeries, antibiotic prophylaxis may minimize infection occurrences in most surgeries except Mohs surgery, simple hand surgery, herniorrhaphy surgery, hepatectomy, thyroid surgery, rhinoplasty, stented distal hypospadias repair, midurethral sling placement, endoscopic sinus surgery, and transurethral resection of bladder tumors with only low to very low certainty evidence. For nonsurgery invasive procedures, only low to very low certainty evidence showed benefits of antibiotic prophylaxis for cystoscopy, postoperative urinary catheterization, and urodynamic study. For medical prophylaxis, antibiotic prophylaxis showed greater benefits in nonemergency scenarios, in which patients were mainly with weakened immune systems, or at risk of recurrent chronic infections. Antibiotics prophylaxis may increase antibiotic resistance or other adverse events in most scenarios and reached significance in cystoscopy, afebrile neutropenia following chemotherapy and hematopoietic stem cell transplantation. Antibiotic prophylaxis in surgical and nonsurgical scenarios is generally effective and seems independent of surgical cleanliness and urgency of diseases. Its safety is not well determined due to lack of available data. Nevertheless, the low quality of current evidence limits the external validity of these findings, necessitating clinicians to judiciously assess indications, balancing low infection rates with antibiotic-related side effects.

PLUS-IS-LESS project: Procalcitonin and Lung UltraSonography-based antibiotherapy in patients with Lower rESpiratory tract infection in Swiss Emergency Departments: study protocol for a pragmatic stepped-wedge cluster-randomized trial

BackgroundLower respiratory tract infections (LRTIs) are among the most frequent infections and a significant contributor to inappropriate antibiotic prescription. Currently, no single diagnostic tool can reliably identify bacterial pneumonia. We thus evaluate a multimodal approach based on a clinical score, lung ultrasound (LUS), and the inflammatory biomarker, procalcitonin (PCT) to guide prescription of antibiotics. LUS outperforms chest X-ray in the identification of pneumonia, while PCT is known to be elevated in bacterial and/or severe infections. We propose a trial to test their synergistic potential in reducing antibiotic prescription while preserving patient safety in emergency departments (ED).MethodsThe PLUS-IS-LESS study is a pragmatic, stepped-wedge cluster-randomized, clinical trial conducted in 10 Swiss EDs. It assesses the PLUS algorithm, which combines a clinical prediction score, LUS, PCT, and a clinical severity score to guide antibiotics among adults with LRTIs, compared with usual care. The co-primary endpoints are the proportion of patients prescribed antibiotics and the proportion of patients with clinical failure by day 28. Secondary endpoints include measurement of change in quality of life, length of hospital stay, antibiotic-related side effects, barriers and facilitators to the implementation of the algorithm, cost-effectiveness of the intervention, and identification of patterns of pneumonia in LUS using machine learning.DiscussionThe PLUS algorithm aims to optimize prescription of antibiotics through improved diagnostic performance and maximization of physician adherence, while ensuring safety. It is based on previously validated tests and does therefore not expose participants to unforeseeable risks. Cluster randomization prevents cross-contamination between study groups, as physicians are not exposed to the intervention during or before the control period. The stepped-wedge implementation of the intervention allows effect calculation from both between- and within-cluster comparisons, which enhances statistical power and allows smaller sample size than a parallel cluster design. Moreover, it enables the training of all centers for the intervention, simplifying implementation if the results prove successful.The PLUS algorithm has the potential to improve the identification of LRTIs that would benefit from antibiotics. When scaled, the expected reduction in the proportion of antibiotics prescribed has the potential to not only decrease side effects and costs but also mitigate antibiotic resistance.Trial registrationThis study was registered on July 19, 2022, on the ClinicalTrials.gov registry using reference number: NCT05463406.Trial statusRecruitment started on December 5, 2022, and will be completed on November 3, 2024. Current protocol version is version 3.0, dated April 3, 2023.

Antimicrobial Prophylaxis in Robot-Assisted Laparoscopic Radical Prostatectomy: A Systematic Review.

It remains unclear whether antibiotic prophylaxis (AP) should be recommended or discouraged in robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer (PCa). The development of microbial resistance and side effects are risks of antibiotic use. This systematic review (SR) investigates the evidence base for AP in RALP. A systematic literature search was conducted until 12 January 2023, using Embase, MEDLINE, Cochrane CENTRAL, Cochrane CDSR (via Ovid) and CINAHL for studies reporting the effect of AP on postoperative infectious complications in RALP. Of 436 screened publications, 8 studies comprising 6378 RALP procedures met the inclusion criteria. There was no evidence of a difference in the rate and severity of infective complications within 30 days after RALP surgery between different AP protocols. No studies omitted AP. For patients who received AP, the overall occurrence of postoperative infectious complications varied between 0.6% and 6.6%. The reported urinary tract infection (UTI) rates varied from 0.16% (4/2500) to 8.9% (15/169). Wound infections were reported in 0.46% (4/865) to 1.12% (1/89). Sepsis/bacteraemia and hyperpyrexia were registered in 0.1% (1/1084) and 1.6% (5/317), respectively. Infected lymphoceles (iLC) rates were 0.9% (3 of 317) in a RALP cohort that included 88.6% pelvic lymph node dissections (PLND), and 3% (26 of 865) in a RALP cohort where all patients underwent PLND. Our findings underscore that AP is being administered in RALP procedures without scientifically proven evidence. Prospective studies that apply consistent and uniform criteria for measuring infectious complications and antibiotic-related side effects are needed to ensure the comparability of results and guidance on AP in RALP.

Evaluating the efficacy of single-shot versus prolonged antibiotic prophylaxis in alveolar cleft osteoplasty – A retrospective cohort study

This retrospective cohort study aimed to compare the outcomes of alveolar cleft osteoplasty using single-shot antibiotic prophylaxis versus a prolonged antibiotic regimen. The primary endpoints assessed were the incidence of infection, failure of surgical correction, and antibiotic-related side effects. Patients with orofacial clefts affecting the alveolar ridge who underwent alveolar cleft osteoplasty at a tertiary care center between 2015 and 2021 were included. The prolonged antibiotic group received extended antibiotic treatment, while the single-shot group received preoperative antibiotics only. Among 83 patients (mean age 12.8 years), 51 interventions were performed under prolonged antibiotic prophylaxis (mean duration 5.82 days) whereas in 40 interventions only single-shot prophylaxis was administered. There were no significant differences in infection frequency, surgical correction failure, implant loss, or adverse events between the groups. However, after single-shot antibiotic regimen, patients had significantly shorter hospital stays, being discharged on average one day earlier. The study suggests that single-shot antibiotic prophylaxis does not have drawbacks compared to prolonged antibiotic treatment in alveolar cleft osteoplasty. Considering increasing antibiotic resistance and potential side effects, omitting prolonged antibiotic prophylaxis is recommended for patients undergoing alveolar cleft osteoplasty.

Challenges and opportunities related to penicillin allergy in the Veterans Health Administration: a narrative review.

The presence of a penicillin allergy label in a patient's medical chart is associated with negative clinical and economic outcomes. Given that less than 10% of reported reactions are truly immunoglobulin E-mediated, removal of unverified penicillin allergy labels is a public health priority and an area of ongoing implementation research. The Veterans Health Administration (VHA) is the largest integrated healthcare system in the United States, with almost 9 million veterans currently enrolled. However, studies analyzing the impact of the penicillin allergy label in this population are limited to single facilities and largely focus on short-term outcomes of allergy documentation correction, usage of β-lactams, and avoidance of antibiotic-related side effects. Broader, national VHA studies focusing on health outcomes and costs are lacking. As with non-VHA facilities, penicillin allergy evaluations are limited owing to the absence of formal allergy/immunology services at most VHA facilities. Pharmacy-driven screening and referral for clinic-based penicillin skin testing is a promising and frequently discussed modality in the literature, but its scalability within the VHA is not yet proven. Broader, evidence-based strategies that can be adapted to the available resources of individual VHA facilities, including those without on-site access to allergy providers, are needed.

Antimicrobial Stewardship Interventions in Pediatric Oncology: A Systematic Review.

Antimicrobial stewardship programs represent efficacious measures for reducing antibiotic overuse and improving outcomes in different settings. Specific data on pediatric oncology are lacking. We conducted a systematic review on the PubMed and Trip databases according to the PRISMA guidelines, searching for reports regarding antimicrobial stewardship in pediatric oncology and hematology patients. The aim of the study was to summarize the present literature regarding the implementation of antimicrobial stewardship programs or initiatives in this particular population, and provide insights for future investigations. Nine papers were included in the qualitative analysis: three regarding antifungal interventions, five regarding antibacterial interventions, and one regarding both antifungal and antibacterial stewardship interventions. Variable strategies were reported among the included studies. Different parameters were used to evaluate the impact of these interventions, including days of therapy per 1000-patient-days, infections with resistant strains, safety analysis, and costs. We generally observed a reduction in the prescription of broad-spectrum antibiotics and an improved appropriateness, with reduced antibiotic-related side effects and no difference in infection-related mortality. Antibiotic stewardship programs or interventions are effective in reducing antibiotic consumption and improving outcomes in pediatric oncology hematology settings, although stewardship strategies differ substantially in different institutions. A standardized approach needs to be implemented in future studies in order to better elucidate the impact of stewardship programs in this category of patients.

The Value of Smoothing

<h3>Introduction</h3> Community-acquired pneumonia (CAP) continues to be a major health problem worldwide and is one of the main reasons for prescribing antibiotics. However, the causative agent is often not identified, resulting in antibiotic overtreatment, which is a key driver of antimicrobial resistance and adverse events. We aim to test the hypothesis that comprehensive molecular testing, compared with routine microbiological testing, would be effective in reducing antibiotic use in patients with CAP. <h3>Methods and analysis</h3> We will perform a randomised, controlled, open-label clinical trial with two parallel groups (1:1) at two tertiary hospitals between 2020 and 2022. Non-severely immunosuppressed adults hospitalised for CAP will be considered eligible. Patients will be randomly assigned to receive either the experimental diagnosis (comprehensive molecular testing plus routine microbiological testing) or standard diagnosis (only microbiological routine testing). The primary endpoint will be antibiotic consumption measured as days of antibiotic therapy per 1000 patient-days. Secondary endpoints will be de-escalation to narrower antibiotic treatment, time to switch from intravenous to oral antibiotics, days to reaching an aetiological diagnosis, antibiotic-related side effects, length of stay, days to clinical stability, intensive care unit admission, days of mechanical ventilation, hospital readmission up to 30 days after randomisation and death from any cause by 48 hours and 30 days after randomisation. We will need to include 440 subjects to be able to reject the null hypothesis that both groups have equal days of antibiotic therapy per 1000 patient-days with a probability &gt;0.8. <h3>Ethics and dissemination</h3> Ethical approval has been obtained from the Ethics Committee of Bellvitge Hospital (AC028/19) and from the Spanish Medicines and Medical Devices Agency, and it is valid for all participating centres under existing Spanish legislation. Results will be presented at international meetings and will be made available to patients, their caregivers and funders. <h3>Trial registration number</h3> ClinicalTrials: NCT04158492. EudraCT: 2018-004880-29.

Panax quinquefolius Polysaccharides Ameliorate Antibiotic-Associated Diarrhoea Induced by Lincomycin Hydrochloride in Rats via the MAPK Signaling Pathways.

American ginseng (Panax quinquefolius L.) is an herbal medicine with polysaccharides as its important active ingredient. The purpose of this research was to identify the effects of the polysaccharides of P. quinquefolius (WQP) on rats with antibiotic-associated diarrhoea (AAD) induced by lincomycin hydrochloride. WQP was primarily composed of galacturonic acid, glucose, galactose, and arabinose. The yield, total sugar content, uronic acid content, and protein content were 6.71%, 85.2%, 31.9%, and 2.1%, respectively. WQP reduced the infiltration of inflammatory cells into the ileum and colon, reduced the IL-1β, IL-6, IL-17A, and TNF-α levels, increased the levels of IL-4 and IL-10 in colon tissues, improved the production of acetate and propionate, regulated the gut microbiota diversity and composition, improved the relative richness of Lactobacillus and Bacteroides, and reduced the relative richness of Blautia and Coprococcus. The results indicated that WQP can enhance the recovery of the intestinal structure in rats, reduce inflammatory cytokine levels, improve short-chain fatty acid (SCFA) levels, promote recovery of the gut microbiota and intestinal mucosal barrier, and alleviate antibiotic-related side effects such as diarrhoea and microbiota dysbiosis caused by lincomycin hydrochloride. We found that WQP can protect the intestinal barrier by increasing Occludin and Claudin-1 expression. In addition, WQP inhibited the MAPK inflammatory signaling pathway to improve the inflammatory status. This study provides a foundation for the treatment of natural polysaccharides to reduce antibiotic-related side effects.

Aminoglycoside or Polymyxin Monotherapy for Treating Complicated Urinary Tract Infections Caused by Extensively Drug-Resistant Pseudomonas aeruginosa: A Propensity Score-Adjusted and Matched Cohort Study.

IntroductionExtensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) infections are difficult to treat. We aimed to compare aminoglycosides or polymyxin monotherapy versus other antibiotic regimens (carbapenems, aztreonam, ceftazidime, cefepime, ceftolozane-tazobactam, or ceftazidime-avibactam) in complicated urinary tract infections (cUTI) caused by XDR-PA.MethodsStudy performed at a tertiary-care hospital from 2010 to 2019. All consecutive adult patients with XDR-PA urine cultures and diagnosed with cUTI were retrospectively reviewed. XDR phenotype was defined according to Magiorakos et al. A propensity score was used as a covariate in multivariate analyses and for matching. Primary outcome was early clinical failure and at end of treatment (EOT). Main secondary outcomes were 30- and 90-day mortality, microbiological clearance, and antibiotic-related side effects.ResultsOf the 465 episodes screened, 101 were included, 48% were treated with aminoglycoside or colistin monotherapy. Most XDR-PA were susceptible to colistin (100%) and amikacin (43%). Patients treated with antibiotic regimens other than aminoglycosides or polymyxin monotherapy were more likely to have hematologic malignancy (p < 0.001), higher SOFA score (p = 0.048), and bacteremia (p = 0.003). In multivariate models adjusted by propensity score, aminoglycoside or colistin monotherapy was not associated with worse outcomes. After propensity score matching, 28 episodes in each treatment group were matched. Adjusted ORs (95% CI) for early clinical failure and at EOT with aminoglycosides or polymyxin monotherapy were 0.53 (0.18–1.58) and 1.29 (0.34–4.83), respectively. Aminoglycoside or colistin monotherapy was not associated with higher 30-day (HR 0.93, 95% CI 0.17–5.08) or 90-day mortality (HR 0.68, 95% CI 0.20–2.31), nor with absence of microbiological clearance (OR 0.72, 95% CI 0.33–1.58). No statistically significant differences were found in terms of nephrotoxicity. Clostridioides difficile infection was observed only in the “other antibiotic regimens” group (n = 6, 11.3%).ConclusionsAminoglycosides or polymyxin monotherapy showed good efficacy and safety profile in treating cUTI caused by XDR-PA. These results may be useful for antibiotic stewardship activities.Electronic Supplementary MaterialThe online version of this article (10.1007/s40121-021-00570-z) contains supplementary material, which is available to authorized users.

Efficacy of Lactobacillus reuteri supplementation therapy for Helicobacter pylori eradication: A meta-analysis of randomised controlled trials

AimsTo investigate the effects of Lactobacillus reuteri supplementation on the eradication rate of H. pylori and the treatment-related adverse effects caused by anti-H. pylori therapies. MethodsThe authors conducted independent searches of PubMed, Medline, Embase and Cochrane library from the inception of this study until May 2021 and extracted data from eligible randomised controlled trials published in English that compared Lactobacillus reuteri supplementation to placebo or no treatment during anti-H. pylori therapies. Review Manager 5.3 was used for all statistical analyses. ResultsSix randomized controlled trials involving 378 patients were included in the analysis. An intention-to-treat analysis via a fixed-effects model showed that the pooled relative risk (RR) for the eradication rate was higher for the Lactobacillus reuteri supplementation group than for the control group, but the difference was not significant [RR 1.12, 95% confidence interval (CI): 0.98–1.27, P ​= ​0.09). The incidence of total antibiotic-related side effects was lower in the Lactobacillus reuteri supplementation group than in the control group, with a pooled RR value of 0.55 (95% CI: 0.39–0.77, P ​= ​0.0006), which was determined using a fixed-effects model. Certain adverse events, such as diarrhoea (RR ​= ​0.31, 95% CI: 0.19–0.52, P ​< ​0.00001), abdominal pain (RR ​= ​0.71, 95% CI: 0.55–0.93, P ​= ​0.01) and constipation (RR ​= ​0.45, 95% CI: 0.25–0.83, P ​= ​0.01), were reported at lower rates in the Lactobacillus reuteri supplementation group than in the control group. ConclusionLactobacillus reuteri supplementation during anti-Helicobacter pylori treatment may not be effective for improving H. pylori eradication rates. However, it can minimize the incidence of therapy-related adverse events and alleviate most disease-related symptoms. Our results should be interpreted with caution due to the lack of enough trials included in this analysis.

296. IV-to-PO Antibiotic Step-down Therapy for Treatment of Uncomplicated Streptococcal Bloodstream Infections

BackgroundBeta-lactams are the drug of choice for uncomplicated Streptococcal bloodstream infections (BSIs). However, due to the low bioavailability of oral beta-lactams, it’s unclear whether de-escalation from IV to PO therapy is safe and effective. Our objective was to compare the efficacy and safety of step-down IV-to-PO antibiotic therapy to IV-only treatment of uncomplicated Streptococcal BSIs.MethodsThis was a retrospective study at a level-1, academic medical center in New Mexico of patients ≥ 18 years of age treated for uncomplicated Streptococcal BSI between January 2017 and December 2019. The primary outcome was clinical failure in patients receiving IV-only therapy compared to IV-to-PO step-down therapy. Clinical failure was defined as having at least one of the following: persistent bacteremia, 30-day reinfection at any site or new-onset sepsis, 30-day BSI recurrence, or 30-day all-cause mortality. Secondary outcomes include 30-day all-cause readmission, 30-day antibiotic-related side effects, 30-day C. difficile-associated diarrhea and hospital length of stay (HLOS).ResultsA total of 98 patients were included: 51 in the IV-to-PO group and 47 in the IV-only therapy group. The median age for both groups was 61 years; 65% patients were male, and 72% were Caucasian. BSIs were predominantly associated with respiratory infections (24.5%). Streptococcus pneumoniae (29.6%) was the most common pathogen. Nine patients (19.1%) in the IV-only group and none in the IV-to PO group experienced a clinical failure. 30-day reinfection at any site or new-onset sepsis (88.9%) was the primary cause of clinical failures. Fourteen patients (14.3%) were readmitted due to any cause within 30 days, 6 patients (11.8%) from the IV-to-PO and 8 (17%) from the IV-only group. Patients in the IV-to-PO group had a shorter duration of therapy than patients in the IV-only group (13 vs. 15 days, p=0.001), and decreased HLOS (5 vs. 12 days, p< 0.001). Clinical failure was not statistically different when assessed for co-morbidities, source of infection, Pitt bacteremia score, documented BSI clearance, ICU admission or pathogen.ConclusionIV-to-PO step-down therapy appears to be a safe and effective alternative for treating uncomplicated Streptococcal BSIs in patients who are otherwise clinical stable.DisclosuresKeenan L. Ryan, PharmD, PhC, Theravance (Advisor or Review Panel member)

The effect of cefoperazone sulbactam and piperacillin tazobactam on mortality in Gram-negative nosocomial infections

Cefoperazone-sulbactam (CS) and piperacillin-tazobactam (TZP) are used in the treatment of Gram-negative nosocomial infections (NIs). We aimed to compare the effects of these two antibiotics on mortality and treatment success. Patients treated with CS or TZP empirically for at least three days with suspicion of NI were included in this retrospective study. In total, 308 (154 patients in both treatment arms) patients were analyzed. Treatment success rate in CS and TZP group respectively (50% vs 51.2%, p = 0.18), 28-day mortality rate (46.1% vs 42.8%, p = 0.56) and antibiotic-related side effects (50.6% vs 46.1%, p = 0.42) were similar except prolonged prothrombin time (19.4% vs 6.4%; p = 0.001). According to this study results, CS and TZP have equal effectivity and safety for the empirical treatment of Gram-negative NIs. CS may be an appropriate alternative to TZP for antibiotic cycling or mixing strategy to reduce antibiotic resistance.

Reasons for Litigation in Arthroplasty Infections and Lessons Learned.

Infections complicate a minority of orthopaedic arthroplasties but are the leading cause of malpractice claims. The basis for the claims is unclear. The objective of this study was to identify the main deviations from current recommendations by reviewing patient files recorded by a major French medical liability-specialized insurance company for private practitioners (MACSF [Mutuelle d'Assurance du Corps de Santé Français]) and to analyze legal claims and outcomes of litigation. All claims data for periprosthetic joint infections were analyzed retrospectively from 2010 to 2014. Treatment strategies were compared with therapeutic guidelines published by medical societies. Forty-five claims for periprosthetic joint infection were recorded; 82% of patients were men and the mean patient age was 63 years. Twenty-one patients (47%) had a knee arthroplasty, 21 had a hip arthroplasty, 2 had a shoulder arthroplasty, and 1 had an ankle arthroplasty. Twenty-three infections (51%) occurred within 1 month postoperatively. Staphylococcus aureus was isolated from intraoperative samples in 36% of the cases (including 25% of these with methicillin-resistant strains), and coagulase-negative staphylococci were isolated in 51% (44% methicillin-resistant strains) of the cases. Treatment lasted for a median of 9.5 months (range, 1.5 to 96 months), with a median of 6 months (range, 1.5 to 20 months) of antibiotics and 3 surgical procedures (range, 0 to 7 surgical procedures). A total of 18% of patients had antibiotic-related side effects, 2% of patients died, and 76% of patients had persistent sequelae. An infectious disease specialist's advice was required for 56% of the patients. Discordances with therapeutic guidelines were found in 76% of the patient files, including delay in diagnosis (44%) and inadequate medical treatment (18%) or medico-surgical treatment (13%). Late diagnosis of early postoperative infections appears to be the major cause of inappropriate management and malpractice litigation. Discordance with current guidelines was identified. Early consultation with an infectious disease specialist may help to reduce malpractice claims. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Procalcitonin and antibiotics in moderate-severe acute exacerbation of chronic obstructive pulmonary disease: to use or not to use.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Acute exacerbations of COPD (AECOPD) are major driver for healthcare utilization with each exacerbation begetting the next exacerbation. It is, therefore, important to treat each episode effectively to prevent the next. However, this can be challenging as AECOPD result from complex interactions between host, environment and infective agents. The benefits of starting antibiotics in AECOPD, which are not life-threatening (e.g. not requiring mechanical ventilation) or not complicated by pneumonia remain controversial. The use of procalcitonin to guide antibiotic therapy in AECOPD has gained interest in recent years. The main advantage of this approach is a safe reduction in antibiotic use in a large group of patients, which may potentially translate to several other benefits. These include reduced antibiotic-related side-effects, reduced risk of developing antibiotic-resistant organisms and cost savings. This approach is associated with no increase in mortality or morbidity such as treatment failure, re-admission, admission to ICU. Procalcitonin-guided antibiotic therapy in AECOPD is a promising and safe approach, which may be ready for the prime time.

KNOWLEDGE, ATTITUDE, AND BEHAVIORS TOWARD ANTIBIOTICS OF NON-MEDICAL STUDENTS JOUF UNIVERSITY, SAUDI ARABIA

Objective: The objective of the study was to investigate the knowledge and attitude of non-medical students, Jouf University toward antibiotic.Methods: Data were collected from male and female students using a self-prepared questionnaire then tabulated and analyzed using SPSS program.Results: This study included 1035 students; 573 (55.3%) male and 462 (44.6%) female, aged (21.5±2.2) years. About 533 (51.5%) used antibiotic during the year 2015. 705 (68.12%) of the student display wrong answer regarding the uses of the antibiotic. 53.5% depending on the previous prescription on self-medicated antibiotic (SAM), followed by their experience (14.5%) and pharmacy advice (11.3%). 45.9% did not have any idea about the antibiotic name they used. Majority of the students (62.6%) stop antibiotic once improvement is achieved, whereas (28.1%) complete the course till the end of the last dose. 75.4% of the studied populations saving at least one antibiotic at home while 62.7% sharing antibiotic with others. 35.3% of the studied population did not experienced antibiotic-related side effects, while 19.3% experience nausea. About 57.6% believed that broad spectrum is better than narrow-spectrum antibiotic, 70.4% deny that higher doses enhance recovery, (57.3%) believes that low dose decrease side effect. 51.9% depend on their good medical knowledge for SMA, while 20.3% was to save time, 18.8% dependent on pharmacy expert where only 9% was to save money cost.Conclusion: The majority of the sample had a fair level of knowledge in relation to antibiotics. Initiation of national program and campaigns toward antibiotic uses to raise the public awareness about the hazardous of antibiotic misuse/abuse is essential to decrease the gap between antibiotic use and attitude.

Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis

In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings. Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects. We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0·83 [95% CI 0·70 to 0·99], p=0·037). This mortality benefit was similar across subgroups by setting and type of infection (pinteractions>0·05), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2·4-day reduction in antibiotic exposure (5·7 vs 8·1 days [95% CI -2·71 to -2·15], p<0·0001) and a reduction in antibiotic-related side-effects (16% vs 22%, adjusted OR 0·68 [95% CI 0·57 to 0·82], p<0·0001). Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance. National Institute for Health Research.

Efficacy of Probiotic Supplementation Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Controlled Trials.

BackgroundTraditional Helicobacter pylori (H. pylori) eradication therapies have shown efficacies below 80% in several studies, and their use has been accompanied by antibiotic-related side effects. Some recent studies have reported that supplementing standard therapies with probiotics can improve the efficacy and tolerability of Helicobacter pylori eradication therapy.ObjectiveTo assess the effects of probiotic supplementation on the eradication rates and therapy-related adverse event rates of anti-Helicobacter pylori regimens.MethodsWe searched PubMed, Medline, the Cochrane Central Registry of Controlled Trials and the Chinese Biomedical Database for eligible randomized controlled trials published through July, 2015. Review Manager 5.3 was used for all statistical analyses.ResultsThirteen randomized controlled trials involving a total of 2306 patients were included in our analysis. Intent-to-treat (ITT) analysis performed using a fixed-effects model (test for heterogeneity I2 = 45%) showed that the pooled relative risk (RR) of eradication was significantly higher in the probiotic supplementation group than in the control group [RR 1.15, 95% confidence interval (CI): 1.10–1.20, P<0.00001]. The incidence of total antibiotic-related side effects was lower in the probiotic supplementation group than in the control group, and the pooled RR (studies n = 9) was 0.71 (95% CI: 0.54–0.94, P = 0.02), as determined using a random-effects model (heterogeneity test I2 = 59%). Certain adverse events, such as nausea and vomiting (RR = 0.58, 95% CI 0.35–0.95, P = 0.03), diarrhea (RR = 0.51, 95% CI: 0.31–0.84, P = 0.008) and constipation (RR = 0.47, 95% CI: 0.28–0.80, P = 0.005), were reported at lower rates in the probiotic supplementation group than in the control group. Subgroup analysis showed that eradication rates were significantly improved in both adults (RR = 1.14, 95% CI: 1.09–1.19, P<0.00001) and children (RR = 1.24, 95% CI: 1.05–1.47, P = 0.01) in the probiotic supplementation group and that no regional differences between Europe (RR = 1.17, 95% CI: 1.09–1.24, P<0.00001) and Asia were present (RR = 1.14, 95% CI: 1.06–1.22, P = 0.0002). However, the total adverse event rate was not decreased in the adult group (RR = 0.80, 95% CI: 0.61–1.04, P = 0.1) or the Asian group (RR = 0.68, 95% CI: 0.39–1.18, P = 0.17). Subgroup analyses examining therapy regimens and treatment durations showed that probiotic supplementation increased eradication rates in the triple-therapy (RR = 1.18, 95% CI: 1.12–1.25, P<0.00001), seven-day treatment (RR = 1.21, 95% CI: 1.12–1.31, P<0.00001) and fourteen-day treatment (RR = 1.13, 95% CI: 1.06–1.20, P = 0.0002) groups. The incidence of antibiotic-related side effects was significantly reduced in all groups, with the exception of the quadruple-therapy subgroup (RR = 1.13, 95% CI: 0.60–2.13, P = 0.07) and the fourteen-day therapy subgroup (RR = 0.96, 95% CI 0.61–1.51, P = 0.86). Supplementation with Lactobacillus alone (RR = 1.24, 95% CI: 1.12–1.38, P<0.0001) or multi-strain probiotics (RR = 1.12, 95% CI 1.07–1.18, P<0.00001) was effective at improving H. pylori eradication rates. However, supplementation with Lactobacillus alone did not significantly decrease the overall incidence of side effects (RR = 0.61, 95% CI: 0.11–3.51, P = 0.58). Our study also showed that probiotic supplementation before, during or after H. pylori eradication therapy improved eradication rates, regardless of supplementation duration. Furthermore, probiotic supplementation during H. pylori treatment reduced the incidence of side effects.ConclusionProbiotic supplementation during anti-Helicobacter pylori treatment may be effective for improving H. pylori eradication rates, minimizing the incidence of therapy-related adverse events and alleviating most disease-related clinical symptoms. However, our results should be interpreted with caution because of the presence of heterogeneity across the trials included in this analysis.

Use of Prophylactic Antibiotics to Prevent Abscess Formation Following Hepatic Ablation in Patients with Prior Enterobiliary Manipulation

IntroductionPrior enterobiliary manipulation confers a high risk for liver abscess formation after hepatic ablation. We aimed to determine if prophylactic antibiotics could prevent post-ablation abscess in patients with a history of hepaticojejunostomy. Materials and MethodsThis single-institution retrospective study identified 262 patients who underwent 307 percutaneous liver ablation sessions between January 2010 and August 2014. Twelve (4.6 %) patients with prior hepaticojejunostomy were included in this analysis. Ten (83> %) had received an aggressive prophylactic antibiotic regimen consisting of levofloxacin, metronidazole, neomycin, and erythromycin base. Two (16.6 %) had received other antibiotic regimens. Clinical, laboratory, and imaging findings were used to identify abscess formation and antibiotic-related side effects. ResultsTwelve ablation sessions were performed during the period studied. During a mean follow-up period of 440 days (range, 77–1784 days), post-ablation abscesses had developed in 2 (16.6 %) patients, who both received the alternative antibiotic regimens. None of the 10 patients who received the aggressive prophylactic antibiotic regimen developed liver abscess. One of the 10 patients who received the aggressive prophylactic antibiotic regimen developed grade 2 antibiotic-related diarrhea and arthralgia. ConclusionAn aggressive regimen of prophylactic antibiotics may be effective in preventing liver abscess formation after liver ablation in patients with prior hepaticojejunostomy.

A multidisciplinary intervention to reduce antibiotic duration in lower respiratory tract infections

Prolonged antibiotic courses are common in patients with lower respiratory tract infections (LRTIs) and contribute to antibiotic resistance and side effects. This study describes a multidisciplinary intervention to reduce antibiotic duration in LRTI patients. This was a prospective before-and-after intervention study conducted from November 2011 to December 2012. Antibiotic duration was recorded for 6 months for all LRTI admissions (pneumonia, exacerbation of chronic obstructive pulmonary disease, exacerbation of asthma, and other LRTIs), followed by the introduction of an intervention intended to reduce the duration of antibiotic treatment. The intervention incorporated an antibiotic duration based on the CURB65 score, automatic stop dates and pharmacist feedback to prescribers. Two hundred and eighty-one patients were included in the pre-intervention group and 221 in the post-intervention group. The intervention resulted in a reduction in the duration of antibiotic treatment from 8.3 to 6.8 days (P < 0.001, 18.1% relative reduction). The rate of antibiotic-related adverse effects reduced from 31% to 19% (P = 0.03, 39.3% relative reduction). There was no increase in mortality or length of stay A simple intervention can significantly reduce antibiotic duration and antibiotic-related side effects.