Bridging the gap: opportunities for transitions of care pharmacist review of outpatient parenteral antimicrobial therapy prescriptions prior to hospital discharge.

Purpose: Pharmacist-led initiatives providing optimization of medications during transitions of care (TOC) have shown to have a positive impact on prescribing practices and patient outcomes. This study aims to evaluate the role and impact of TOC pharmacist review of outpatient parenteral antimicrobial therapy (OPAT) prescriptions prior to hospital discharge. Methods: In a retrospective chart review, patients with OPAT prescriptions between November 1, 2022 and January 31, 2023 were evaluated using prescription-specific and intervention-specific data points. Prescription-specific data points included intravenous antimicrobials prescribed, indication, prescribing team, and time from OPAT prescription to TOC pharmacist review. Intervention-specific data points included antimicrobial optimization (dose/frequency, duration, and other), prescription clarification, and laboratory monitoring. Results: Of the 137 OPAT prescriptions evaluated, 67 required intervention by TOC pharmacists (48.9%). The General Infectious Disease Consult team placed 71.5% of OPAT prescriptions and required interventions less frequently (42.9%) compared to the other teams. Antimicrobial optimization interventions accounted for 54.2% of interventions, which were primarily related to medication dose and frequency. Conclusion: The TOC pharmacists can play a key role in the evaluation of OPAT prescriptions at hospital discharge. This intervention demonstrated how TOC pharmacists can effectively collaborate with the OPAT team, which builds on prior evidence of the role and value of pharmacists in the transitional care setting.

Identification of Risk Factors for Intra-Abdominal Candidiasis.

Background: Intra-abdominal candidiasis (IAC) is associated with substantial morbidity and mortality in hospitalized patients. Identifying high-risk populations may facilitate early and selective directed therapy in appropriate patients and avoid unwarranted treatment and any associated adverse effects in those who are low risk. Patients and Methods: This retrospective, case-control study included patients >18 years of age admitted from July 1, 2010 to July 1, 2021 who had a microbiologically confirmed intra-abdominal infection (gastrointestinal culture positive for either a Candida spp. [cases] or bacterial isolate [controls] collected intra-operatively or from a drain placed within 24 hours). Patients receiving peritoneal dialysis treatment or with a peritoneal dialysis catheter in place or treated at an outside hospital were excluded. Multivariable regression was utilized to identify independent risk factors for the development of IAC. Results: Five hundred twenty-three patients were screened, and 250 met inclusion criteria (125 per cohort). Multivariable analysis identified exposure to corticosteroids (odds ratio [OR], 5.79; 95% confidence interval [CI], 2.52-13.32; p < 0.0001), upper gastrointestinal tract surgery (OR, 3.51; 95% CI, 1.25-9.87; p = 0.017), and mechanical ventilation (OR, 3.09; 95% CI 1.5-6.37; p = 0.002) were independently associated with IAC. The area under the receiver operating characteristic (AUROC) and goodness of fit were 0.7813 and p = 0.5024, respectively. Conclusions: Exposure to corticosteroids, upper gastrointestinal tract surgery, and mechanical ventilation are independent risk factors for the development of microbiologically confirmed IAC suggesting these factors may help identify high-risk individuals requiring antifungal therapy.

Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence. Objective: To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength. Evidence Review: This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches. Findings: A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)-only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions. Conclusions and Relevance: In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed.

Ceftolozane/tazobactam heteroresistance in cystic fibrosis-related Pseudomonas aeruginosa infections.

Objectives: Cystic fibrosis (CF) patients are often colonized with Pseudomonas aeruginosa. During treatment, P. aeruginosa can develop subpopulations exhibiting variable in vitro antimicrobial (ABX) susceptibility patterns. Heteroresistance (HR) may underlie reported discrepancies between in vitro susceptibility results and clinical responses to various ABXs. Here, we sought to examine the presence and nature of P. aeruginosa polyclonal HR (PHR) and monoclonal HR (MHR) to ceftolozane/tazobactam in isolates originating from CF pulmonary exacerbations. Methods: This was a single-centre, non-controlled study. Two hundred and forty-six P. aeruginosa isolates from 26 adult CF patients were included. PHR was defined as the presence of different ceftolozane/tazobactam minimum inhibitory concentration (MIC) values among P. aeruginosa isolates originating from a single patient specimen. Population analysis profiles (PAPs) were performed to assess the presence of MHR, defined as ≥4-fold change in the ceftolozane/tazobactam MIC from a single P. aeruginosa colony. Results: Sixteen of 26 patient specimens (62%) contained PHR P. aeruginosa populations. Of these 16 patients, 6 (23%) had specimens in which PHR P. aeruginosa isolates exhibited ceftolozane/tazobactam MICs with categorical differences (i.e. susceptible versus resistant) compared to results reported as part of routine care. One isolate, PSA 1311, demonstrated MHR. Canonical ceftolozane/tazobactam resistance genes were not found in the MHR isolates (MHR PSA 1311 or PHR PSA 6130). Conclusions: Ceftolozane/tazobactam PHR exists among P. aeruginosa isolates in this work, and approximately a quarter of these populations contained isolates with ceftolozane/tazobactam susceptibiilty interpretations different from what was reported clinically, supporting concerns surrounding the utility of traditional susceptibility testing methodology in the setting of CF specimens. Genome sequencing of isolates with acquired MHR to ceftolozane/tazobactam revealed variants of unknown significance. Future work will be centred on determining the significance of these mutations to better understand these data in clinical context.

Probable Encephalopathy and Spasticity in a Multiple Sclerosis Patient Following Carbapenem Administration: A Case Report and Brief Literature Review.

Purpose: The purpose of this case report is to describe spasticity and encephalopathy that developed in a multiple sclerosis patient following carbapenem administration. Summary: A 55-year-old female with multiple sclerosis developed spasticity and encephalopathy within 24 hours of meropenem and ertapenem administration. This was the second time that she had developed encephalopathy following carbapenem administration. The patient gradually recovered over four days following discontinuation of carbapenem therapy. Conclusion: Carbapenem neurotoxicity, a well-documented adverse effect, has been linked to several risk factors, including central nervous system lesions. Despite this, there is little evidence describing the risk of neurotoxicity in patients with multiple sclerosis. It is important to understand the potential adverse effects of carbapenems in specific patient populations to help guide appropriate treatment of infections.

Derivation and Validation of a Clinical Prediction Score to Identify the Isolation of Pseudomonas in Pneumonia.

Given the focus of existing clinical prediction scores on identifying drug-resistant pathogens as a whole, the application to individual pathogens and other institutions may yield weaker performance. This study aimed to develop a locally derived clinical prediction model for Pseudomonas-mediated pneumonia. This retrospective study included patients ≥18 years of age who were admitted to an academic medical center between 1 July 2010 and 31 July 2020 with a CDC National Healthcare Safety Network confirmed pneumonia diagnosis and were receiving antimicrobials during the index encounter, with a positive respiratory culture. Cystic fibrosis patients were excluded. Logistic regression analysis identified risk factors associated with the isolation of Pseudomonas aeruginosa from respiratory cultures within the derivation cohort (n = 186), which were weighted to generate a prediction score that was applied to the derivation and internal validation (n = 95) cohorts. A total of 281 patients met the inclusion criteria. Five predictor variables were identified, namely, tracheostomy status (4 points), chronic obstructive pulmonary disease (5 points), enteral nutrition (9 points), chronic steroid use (11 points), and Pseudomonas aeruginosa isolation from any culture in the prior 6 months (14 points). At a score of >11, the prediction score demonstrated a sensitivity of 52.4% (95% confidence interval [CI], 36.4 to 68.0%) and a specificity of 84.9% (95% CI, 72.4 to 93.35%) in the validation cohort. Score accuracy was 70.5% (95% CI, 60.3 to 79.4%), and the area under the receiver operating characteristic curve (AUROC) was 0.77 (95% CI, 0.68 to 0.87) in the validation cohort. A prediction score for identifying Pseudomonas aeruginosa in pneumonia was derived, which may have the potential to decrease the use of broad-spectrum antibiotics. Validation with larger and external cohorts is necessary. IMPORTANCE In this study, we aimed to develop a locally derived clinical prediction model for Pseudomonas-mediated pneumonia. Utilizing a locally validated prediction score may help direct therapeutic management and be generalizable to other clinical settings and similar populations for the selection of appropriate antimicrobial coverage when data are lacking. Our study highlights a unique patient population, including immunocompromised, structural lung disease, and transplant patients. Five predictor variables were identified, namely, tracheostomy status, chronic obstructive pulmonary disease, enteral nutrition, chronic steroid use, and Pseudomonas aeruginosa isolation from any culture in the prior 6 months. A prediction score for identifying Pseudomonas aeruginosa in pneumonia was derived, which may have the potential to decrease the use of broad-spectrum antibiotics, although validation with larger and external cohorts is necessary.

Ceftaroline versus vancomycin for treatment of acute pulmonary exacerbations of cystic fibrosis in adults.

OBJECTIVES: Vancomycin remains a first-line treatment for methicillin-resistant Staphylococcus aureus (MRSA)-mediated acute pulmonary exacerbations (APEs) in adult cystic fibrosis (CF) patients; however, optimal alternatives remain poorly defined. The aim of this study was to determine the safety and efficacy of ceftaroline for MRSA-mediated APEs of CF in adults. METHODS: We conducted a retrospective, observational cohort study comparing ceftaroline with vancomycin for the treatment of MRSA-mediated APEs in adult CF patients. The primary endpoint was the return to at least 90% of baseline lung function measured by discharge FEV1% predicted in comparison with baseline FEV1% predicted. RESULTS: A total of 55 patients were included in the analysis (22 receiving ceftaroline and 33 receiving vancomycin). Of the patients included in the analysis, 13 patients (59%) in the ceftaroline group and 24 patients (73%) in the vancomycin group met the primary outcome (P = 0.38). FEV1 measurements at baseline, admission and discharge were not different between treatments. Secondary outcomes including 30-day re-admission rate, 30-day mortality, treatment duration and adverse events (neutropenia, Clostridioides difficile infection and acute kidney injury) were similar between groups. CONCLUSION: Our small cohort study supports ceftaroline as an alternative treatment option for MRSA-mediated APE of CF in adults.

Therapeutic Options for Coronavirus Disease 2019 (COVID-19): Where Are We Now?

PURPOSE OF REVIEW: Rapidly evolving treatment paradigms of coronavirus disease 2019 (COVID-19) introduce challenges for clinicians to keep up with the pace of published literature and to critically appraise the voluminous data produced. This review summarizes the clinical evidence from key studies examining the place of therapy of recommended drugs and management strategies for COVID-19. RECENT FINDINGS: The global magnitude and duration of the pandemic have resulted in a flurry of interventional treatment trials evaluating both novel and repurposed drugs targeting various aspects of the viral life cycle. Additionally, clinical observations have documented various stages or phases of COVID-19 and underscored the importance of timing for the efficacy of studied therapies. Since the start of the COVID-19 pandemic, many observational, retrospective, and randomized controlled studies have been conducted to guide management of COVID-19 using drug therapies and other management strategies. Large, randomized, or adaptive platform trials have proven the most informative to guide recommended treatments to-date. Antimicrobial stewardship programs can play a pivotal role in ensuring appropriate use of COVID-19 therapies based on evolving clinical data and limiting unnecessary antibiotics given low rates of co-infection. SUMMARY: Given the rapidly evolving medical literature and treatment paradigms, it is recommended to reference continuously updated, curated guidelines from national and international sources. While the drugs and management strategies mentioned in this review represent the current state of recommendations, many therapies are still under investigation to further define optimal COVID-19 treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11908-021-00769-8.

Bronchoalveolar Lavage Gram Stains for Early Bacterial Identification in Pneumonia: Should They Stay or Should They Go?

OBJECTIVES: The primary endpoint was to determine the sensitivity and specificity of the bronchoalveolar lavage Gram stain in predicting culture results. Secondary endpoints included determining the proportion of Gram stains from bronchoalveolar lavages that accurately identify culture isolates and the duration of antibiotic treatment before bronchoalveolar lavage collection. DESIGN: Retrospective, observational study. SETTING: Four ICUs at a single academic medical center. SUBJECTS: Patients at least 18 years old admitted to an ICU with a diagnosis of pneumonia, collection of a bronchoalveolar lavage sample, and receipt of antibiotics. MEASUREMENTS AND MAIN RESULTS: Two-hundred five isolates were included. Gram stains for Gram-positive and Gram-negative isolates showed high specificity, 97.3% and 100%, respectively, but lower sensitivity at 61.9% and 54.2%, respectively. The positive predictive value and negative predictive value were 77.2% and 95.7% for Gram-positive isolates and 100% and 84.4% for Gram-negative isolates, respectively. Gram stains correctly identified isolates on the bronchoalveolar lavage culture in 61.9% of Gram-positive organisms and in 54.2% of Gram-negative organisms. CONCLUSIONS: Gram stains accurately identified causative organisms in a limited number of patients making the utility of the Gram stain an uncertain modality for predicting causative respiratory pathogens from bronchoalveolar lavage samples.

Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review.

IMPORTANCE: The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. OBSERVATIONS: No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. CONCLUSIONS AND RELEVANCE: The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.

Role of Empiric Anti-Fungal Therapy in the Treatment of Perforated Peptic Ulcer Disease: Review of the Evidence and Future Directions.

Background: Peptic ulcer disease (PUD) affects four million people worldwide. Perforated peptic ulcer (PPU) occurs in less than 15% of cases but is associated with significant morbidity and mortality rates. Administration of antibiotics is standard treatment for gastrointestinal perforations, including PPU. Although fungal growth is common in peritoneal fluid cultures from patients with PPU, current data suggest empiric anti-fungal therapy fails to improve outcomes. To examine the role of anti-fungal agents in the treatment of PPU, the Surgical Infection Society hosted an Update Symposium at its 37th Annual Meeting. Here, we provide a synopsis of the symposium's findings and a brief review of prospective and retrospective reports on the subject. Methods: A search of Pubmed/MEDLINE, EMBASE, and the Cochrane Library was performed between January 1, 2000, and November 1, 2018, comparing outcomes of PPU following empiric anti-fungal treatment versus no anti-fungal therapy. We used the search terms "perforated peptic ulcer," "gastroduodenal ulcer," "anti-fungal," and "perforated" or "perforation." Results: There are no randomized clinical trials comparing outcomes specifically for patients with PPU treated with or without empiric anti-fungal therapy. We identified one randomized multi-center trial evaluating outcomes for patients with intra-abdominal perforations, including PPU, that were treated with or without empiric anti-fungal therapy. We identified one single-center prospective series and three additional retrospective studies comparing outcomes for patients with PPU treated with or without empiric anti-fungal therapy. Conclusion: The current evidence reviewed here does not demonstrate efficacy of anti-fungal agents in improving outcomes in patients with PPU. As such, we caution against the routine use of empiric anti-fungal agents in these patients. Further studies should help identify specific subpopulations of patients who might derive benefit from anti-fungal therapy and help define appropriate treatment regimens and durations that minimize the risk of resistance, adverse events, and cost.

Actinomyces turicensis Necrotizing Soft-Tissue Infection of the Thigh in a Diabetic Male.

Background: Necrotizing soft-tissue infections are a devastating infection that is rarely caused by Actinomyces spp. Case Report: A 45-year-old obese previously healthy male presented to the emergency department with diabetic ketoacidosis. The patient developed systemic signs of infections and right medial thigh pain subsequently diagnosed as a necrotizing soft-tissue infection. Successful treatment included prompt surgical intervention and initiation of broad-spectrum antimicrobial drugs. Conclusion: Actinomyces turicensis may be the pathogen causing certain necrotizing soft-tissue infections. Clinicians should consider the possibility that this organism represents a true pathogen and not colonization/contamination.

Antibiotics versus No Antibiotics for the Treatment of Acute Uncomplicated Diverticulitis: Review of the Evidence and Future Directions.

BACKGROUND: Acute diverticulitis occurs in 25% of individuals with diverticular disease and is associated with significant morbidity and mortality rates. Disease severity is classified as uncomplicated or complicated, with the latter including perforation, fistula, obstruction, or distant abscess. Uncomplicated diverticulitis often improves without surgery or invasive therapies. Administration of antibiotics is a standard of care for treatment of acute uncomplicated diverticulitis. However, recent data suggest antibiotics do not influence outcomes significantly. To address these conflicting approaches, the Surgical Infection Society hosted an Update Symposium at its 37th Annual Meeting examining the role of antibiotics in the treatment of acute uncomplicated diverticulitis. Here, we provide a synopsis of the symposium's findings and a brief review of recent prospective and randomized clinical trials on the topic. METHODS: A search of Embase, MEDLINE, and the Cochrane Library was performed for prospective series and randomized clinical trials published between January 1, 2010, and January 1, 2018, comparing outcomes of antibiotic versus no antibiotic therapy for acute uncomplicated diverticulitis. RESULTS: We identified two single-center prospective series and two randomized clinical trials comparing outcomes for patients with acute uncomplicated diverticulitis treated with antibiotics versus no antibiotics. CONCLUSION: Current evidence does not support administration of antibiotics to improve outcomes in carefully selected healthy patients with acute uncomplicated left-sided diverticulitis. Further studies should help identify specific subpopulations of patients who would derive benefit from antibiotic therapy and help define appropriate antibiotic regimens and treatment durations that minimize cost, adverse effects, and risk of anti-microbial resistance.

Measuring Provider Compliance with an Institution-Based Clinical Pathway for Diverticulitis Using Radiologic Criteria.

BACKGROUND: Diverticulitis remains a common disease encountered in the acute care setting. Management strategies have been developed to guide treatment decisions based on imaging. By using a multi-faceted clinical pathway approach, a standardized method of diagnosing and categorizing disease severity can be performed in order to guide appropriate management. This study evaluated provider compliance with an institutional clinical pathway designed to guide management of diverticulitis. METHODS: An institutional clinical pathway was developed to manage diverticulitis, including radiologic classification, primary service line assignment, interventional strategies, and antimicrobial treatment. To assess provider compliance with the algorithm, we queried the institutional acute diverticulitis database for patients admitted from May 19, 2016 to February 8, 2017, which identified 83 patients. Provider compliance with the pathway was assessed using subgroup analysis of radiologic documentation (modified Neff [mNeff] classification), primary service assignment, and interventions (i.e., interventional radiology [IR] and antimicrobial agents). RESULTS: The cohort represented a diverse group of mNeff classifications, predominantly Stage 0. Surgical interventions occurred in 10.8% of the cohort. Antimicrobial agents were administered to 88.0% and 78.3% of the outpatients and inpatients, respectively. Patients received a total duration of antimicrobial therapy (mean ± standard deviation [SD]) of 10.2 ± 5.1 days. Overall compliance occurred in 10% of the patients. Compliance with radiologic documentation, antimicrobial choice, and antimicrobial duration were 90.4%, 20.5%, and 69.9%, respectively. CONCLUSIONS: Overall compliance with the clinical pathway was poor, except as it related to compliance with radiologic documentation, appropriate assignment to surgical service line, and antimicrobial duration. These results suggest areas for future improvement to augment compliance with the clinical pathway.

Does Isolation of Enterococcus Affect Outcomes in Intra-Abdominal Infections?

BACKGROUND: Enterococci are isolated frequently as pathogens in patients with intra-abdominal infections (IAIs) and may predict poor clinical outcomes. It remains controversial whether enterococci warrant an altered treatment approach with regard to antimicrobial treatment. PATIENTS AND METHODS: The study population was derived from the Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial database. Through post hoc analysis subjects were stratified into two groups based on isolation of Enterococcus. Fifty subjects of the cohort (n = 518) had Enterococcus isolated. Uni-variable and multi-variable analyses were conducted to determine whether isolation of Enterococcus constituted an independent predictor of the pre-defined STOP-IT composite outcome (surgical site infection, recurrent IAI, or death) and the individual components of the composite outcome. RESULTS: From the cohort of 50 subjects, we identified 52 isolates of Enterococcus spp. with a predominance of Enterococcus faecalis (40%) followed by other Enterococcus spp. (37%) and Enterococcus faecium (17%). Baseline demographic characteristics were statistically similar between the two groups. Antibiotic utilization distribution remained balanced between the Enterococcus and no Enterococcus groups with the majority receiving piperacillin-tazobactam (62% and 54%, respectively). The groups had comparable infection characteristics including setting of acquisition (>50% community acquired) and origin of infection (predominantly colon or rectum). Individual and composite clinical outcomes were not different statistically between the Enterococcus and no Enterococcus groups: surgical site infection (10% vs. 7.5%; p = 0.53), recurrent IAI (20% vs. 14.1%; p = 0.26), death (2% vs. 1%; p = 0.40), and composite of all three (30% vs. 20.9%; p = 0.14], respectively. Multi-variable analysis revealed that isolation of Enterococcus did not predict independently the incidence of the composite outcome (odds ratio [OR] 1.53 [95% confidence interval {CI} = 0.78-3.01]; p = 0.22; c-statistic = 0.65; goodness of fit, p = 0.71). CONCLUSIONS: Enterococcus was not a more common pathogen in health-care-associated IAIs and was not an independent risk factor for the composite outcome. The isolation of Enterococcus from IAIs may not warrant an alternative treatment approach but larger studies are needed to validate these findings.

Antibiotics vs. Appendectomy for Acute Uncomplicated Appendicitis in Adults: Review of the Evidence and Future Directions.

BACKGROUND: Acute appendicitis is the most common abdominal surgical emergency in the United States, with a lifetime risk of 7%-8%. The treatment paradigm for complicated appendicitis has evolved over the past decade, and many cases now are managed by broad-spectrum antibiotics. We determined the role of non-operative and operative management in adult patients with uncomplicated appendicitis. METHODS: Several meta-analyses have attempted to clarify the debate. Arguably the most influential is the Appendicitis Acuta (APPAC) Trial. RESULTS: According to the non-inferiority analysis and a pre-specified non-inferiority margin of -24%, the APPAC did not demonstrate non-inferiority of antibiotics vs. appendectomy. Significantly, however, the operations were nearly always open, whereas the majority of appendectomies in the United States are done laparoscopically; and laparoscopic and open appendectomies are not equivalent operations. Treatment with antibiotics is efficacious more than 70% of the time. However, a switch to an antimicrobial-only approach may result in a greater probability of antimicrobial-associated collateral damage, both to the host patient and to antibiotic susceptibility patterns. A surgery-only approach would result in a reduction in antibiotic exposure, a consideration in these days of focus on antimicrobial stewardship. CONCLUSION: Future studies should focus on isolating the characteristics of appendicitis most susceptible to antibiotics, using laparoscopic operations as controls and identifying long-term side effects such as antibiotic resistance or Clostridium difficile colitis.

Age and Its Impact on Outcomes with Intra-Abdominal Infection.

BACKGROUND: Age has been shown to play a significant role in the etiology of complicated intra-abdominal infections (cIAIs), but the correlation between age and outcomes after therapy was not investigated in the Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial. PATIENTS AND METHODS: Data were obtained by post hoc analysis of the STOP-IT trial database. Patients were stratified by age <65 or ≥65 years. Primary outcomes were surgical site infection (SSI), recurrent IAI (recIAI), and death. Multivariable analysis was performed to identify independent predictors of outcomes. RESULTS: There were 398 subjects <65 and 120 ≥ 65 years. Overall baseline characteristics of the two groups were similar. The site of infection was similar between groups except: Colon or rectum (48.3% vs. 29.9%, p = 0.0002) and biliary tree (16.7% vs. 9.1%, p = 0.02), which were more common in the older group, whereas small intestine (6.7% vs. 16.3%, p = 0.008) and appendix (4.2% vs.17.1%, p = 0.0004) were more common in the younger group. Among the primary outcomes, only death was significantly different between the age groups and was more prevalent in the ≥65 years group (4 [3.3%] vs. 1 [0.3%], p = 0.01). Surgical site infection (9.2% vs. 7.3%, p = 0.50), recIAI (15.8% vs. 14.4%, p = 0.69), and a composite outcome (26.7% vs. 20.4%, p = 0.14) were statistically similar between the age groups, and this remained true when controlling for other co-variables. Multivariable analyses did not reveal age as an independent predictor of the composite or individual outcomes. CONCLUSION: Patients with a more advanced age demonstrated variable sources of infection relative to the younger cohort, yet received similar treatments. Patient age was not an independent predictor of the undesired cIAI outcomes. These findings suggest that advanced age itself does not play a significant role in predicting these adverse outcomes for cIAIs and does not necessitate an altered treatment tactic.

Inclusion of Vancomycin as Part of Broad-Spectrum Coverage Does Not Improve Outcomes in Patients with Intra-Abdominal Infections: A Post Hoc Analysis.

BACKGROUND: Management of complicated intra-abdominal infections (cIAIs) includes broad-spectrum antimicrobial coverage and commonly includes vancomycin for the empiric coverage of methicillin-resistant Staphylococcus aureus (MRSA). Ideally, culture-guided de-escalation follows to promote robust antimicrobial stewardship. This study assessed the impact and necessity of vancomycin in cIAI treatment regimens. PATIENTS AND METHODS: A post hoc analysis of the Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial was performed. Patients receiving piperacillin-tazobactam (P/T) and/or a carbapenem were included with categorization based on use of vancomycin. Univariate and multivariable analyses evaluated effects of including vancomycin on individual and the composite of undesirable outcomes (recurrent IAI, surgical site infection [SSI], or death). RESULTS: The study cohort included 344 patients with 110 (32%) patients receiving vancomycin. Isolation of MRSA occurred in only eight (2.3%) patients. Vancomycin use was associated with a similar composite outcome, 29.1%, vs. no vancomycin, 22.2% (p = 0.17). Patients receiving vancomycin had (mean [standard deviation]) higher Acute Physiology and Chronic Health Evaluation II scores (13.1 [6.6] vs. 9.4 [5.7], p < 0.0001), extended length of stay (12.6 [10.2] vs. 8.6 [8.0] d, p < 0.001), and prolonged antibiotic courses (9.1 [8.0] vs. 7.1 [4.9] d, p = 0.02). After risk adjustment in a multivariate model, no significant difference existed for the measured outcomes. CONCLUSIONS: This post hoc analysis reveals that addition of vancomycin occurred in nearly one third of patients and more often in sicker patients. Despite this selection bias, no appreciable differences in undesired outcomes were demonstrated, suggesting limited utility for adding vancomycin to cIAI treatment regimens.