Antibiotic Regimens Research Articles

National variation in prophylactic antibiotic use for elective primary total joint replacement.

Prophylactic antibiotic regimens for elective primary total hip and knee arthroplasty vary widely across hospitals and trusts in the UK. This study aimed to identify antibiotic prophylaxis regimens currently in use for elective primary arthroplasty across the UK, establish variations in antibiotic prophylaxis regimens and their impact on the risk of periprosthetic joint infection (PJI) in the first-year post-index procedure, and evaluate adherence to current international consensus guidance. The guidelines for the primary and alternative recommended prophylactic antibiotic regimens in clean orthopaedic surgery (primary arthroplasty) for 109 hospitals and trusts across the UK were sought by searching each trust and hospital's website (intranet webpages), and by using the MicroGuide app. The mean cost of each antibiotic regimen was calculated using price data from the British National Formulary (BNF). Regimens were then compared to the 2018 Philadelphia Consensus Guidance, to evaluate adherence to international guidance. The primary choice and dosing of the prophylactic antimicrobial regimens varied widely. The two most used regimens were combined teicoplanin and gentamicin, and cefuroxime followed by two or three doses of cefuroxime eight-hourly, recommended by 24 centres (22.02%) each. The alternative choice and dosing of the prophylactic antimicrobial regimen also varied widely across the 83 centres with data available. Prophylaxis regimens across some centres fail to cover the likeliest causes of surgical site infection (SSI). Five centres (4.59%) recommend co-amoxiclav, which confers no Staphylococcus coverage, while 33 centres (30.28%) recommend cefuroxime, which confers no Enterococcus coverage. Limited adherence to 2018 Philadelphia Consensus Guidance was observed, with 67 centres (61.50%) not including a cephalosporin in their guidance. This analysis of guidance on antimicrobial prophylaxis in primary arthroplasty across 109 hospitals and trusts in the UK has identified widespread variation in primary and alternative antimicrobial regimens currently recommended.

Infections After Adoption of Antibiogram-directed Prophylaxis and Intracorporeal Urinary Diversion for Robot-assisted Radical Cystectomy

BackgroundEnhanced recovery after surgery (ERAS) has significantly decreased the morbidity associated with radical cystectomy. However, infectious complications including sepsis, urinary tract (UTIs), wound (WIs), and intra-abdominal (AIs) infections remain common. ObjectiveTo assess whether intracorporeal urinary diversion (ICUD) and antibiogram-directed antimicrobial prophylaxis would decrease infections after robotic-assisted radical cystectomy (RARC). Design, setting, and participantsA retrospective analysis was performed of a prospectively maintained database of patients undergoing RARC between 2014 and 2022 at a tertiary care institution, identifying two groups based on adherence to a prospectively implemented modified ERAS protocol for RARC: modified-ERAS—ICUD and antibiogram-directed ampicillin-sulbactam, gentamicin, and fluconazole prophylaxis were utilized (from January 2019 to present time), and unmodified-ERAS—extracorporeal urinary diversion (UD) and guideline-recommended cephalosporin-based prophylaxis regimen were utilized (from November 2014 to June 2018). Patients receiving other prophylaxis regimens were excluded. InterventionICUD and antibiogram-directed infectious prophylaxis. Outcome measurements and statistical analysisThe primary outcome was UTIs within 30 and 90 d postoperatively. The secondary outcomes were WIs, AIs, and sepsis within 30 and 90 d postoperatively, and Clostridioides difficile infection (CDI) within 90 d postoperatively. Results and limitationsA total of 396 patients were studied (modified-ERAS: 258 [65.2%], unmodified-ERAS: 138 [34.8%]). UD via a neobladder was more common in the modified-ERAS cohort; all other intercohort demographic differences were not statistically different. Comparing cohorts, modified-ERAS had significantly reduced rates of 30-d (7.8% vs 15.9%, p = 0.027) and 90-d UTIs (11.2% vs 25.4%, p = 0.001), and 30-d WIs (1.2% vs. 8.7%, p < 0.001); neither group had a WI after 30 d. Rates of AIs, sepsis, and CDI did not differ between groups. On multivariate regression, the modified-ERAS protocol correlated with a reduced risk of UTIs and WIs (all p < 0.01). The primary limitation is the retrospective study design. ConclusionsUtilization of ICUD and antibiogram-based prophylaxis correlates with significantly decreased UTIs and WIs after RARC. Patient summaryIn this study of infections after robotic radical cystectomy for bladder cancer, we found that intracorporeal (performed entirely inside the body) urinary diversion and an institution-specific antibiogram-directed antibiotic prophylaxis regimen led to fewer urinary tract infections and wound infections at our institution.

Impact of Board Certified Psychiatric Pharmacists on improving urinary tract infection antibiotic appropriateness at an acute psychiatric hospital.

Urinary tract infections (UTIs) are one of the most common indications for antibiotic use; patients with psychiatric disorders have a greater risk for UTI compared with patients without these disorders. However, there is little guidance on how best to manage antibiotic therapy in psychiatric hospitals. This study assessed the impact of a Board Certified Psychiatric Pharmacist (BCPP)-driven guideline on managing UTI treatment in an acute psychiatric hospital. The guideline was developed by the psychiatric pharmacy team and distributed to internists, psychiatrists, and pharmacists. Preintervention data were assessed for patients admitted between November 30, 2019, and February 23, 2020; postintervention data were assessed from February 25, 2020, to April 24, 2020. All patients ages 13 years and older who were admitted and had orders for an antibiotic to treat a UTI were included in this study. Appropriate UTI management was defined as an appropriate agent, dose, route, and frequency per the treatment guideline. Additionally, the following criteria were to be ordered and assessed to be deemed appropriate: urinalysis, urine culture, complete blood count, basic or complete metabolic panel, temperature, and subjective symptoms. Before intervention, 19.0% of antibiotic orders were appropriate; after intervention, 46.7% of antibiotic orders were appropriate (P = .048). The implementation of a BCPP-driven treatment algorithm was associated with a significant increase in appropriate antibiotic regimens for the treatment of UTIs in patients admitted to a psychiatric hospital.

11 Examining antibiotic regimen spectrum and clinical outcomes of pulmonary exacerbation treatment

11 Examining antibiotic regimen spectrum and clinical outcomes of pulmonary exacerbation treatment

Overview of Peptic Ulcer along with its Conventional and Improvement Therapies: A Study of Glycopyrrolate and Management of Peptic Ulcer

Peptic ulcer disease remains a prevalent gastrointestinal disorder globally, posing significant challenges in its management. This comprehensive review provides an overview of peptic ulcer pathology, conventional treatment modalities, and recent advancements in therapeutic approaches. Traditional treatments, among them histamine receptor antagonists, proton pump inhibitors, and antibiotic regimens, have shown efficacy in ulcer healing and symptom alleviation. However, emerging evidence suggests limitations such as drug resistance and adverse effects. In light of these challenges, this article delves into the potential of Glycopyrrolate, a muscarinic receptor antagonist, as a novel therapeutic agent for peptic ulcer management. However, still there may be aggravation of peptic ulcer leading to severe conditions like perforated gastric ulcer, and gastric bleeding where surgery is only beneficial.

In Vivo Emergence of Pandrug-Resistant Acinetobacter baumannii Strain: Comprehensive Resistance Characterization and Compassionate Use of Sulbactam-Durlobactam.

The treatment of patients with infection secondary to carbapenem-resistant Acinetobacter baumannii with emerging cefiderocol resistance remains challenging and unclear. We present a case of in vivo emergence of pandrug-resistant A baumannii that was successfully treated with the compassionate use of investigational sulbactam-durlobactam-based antibiotic regimen. We also performed a longitudinal genomic analysis of the bacterial isolates and showed the development of resistance and genetic mutations over time.

Repurposing of statins for Buruli Ulcer treatment: antimicrobial activity against Mycobacterium ulcerans.

Mycobacterium ulcerans causes Buruli Ulcer, a neglected infectious skin disease that typically progresses from an early non-ulcerative lesion to an ulcer with undermined edges. If not promptly treated, these lesions can lead to severe disfigurement and disability. The standard antibiotic regimen for Buruli Ulcer treatment has been oral rifampicin combined with intramuscular streptomycin administered daily for 8 weeks. However, there has been a recent shift toward replacing streptomycin with oral clarithromycin. Despite the advantages of this antibiotic regimen, it is limited by low compliance, associated side effects, and refractory efficacy for severe ulcerative lesions. Therefore, new drug candidates with a safer pharmacological spectrum and easier mode of administration are needed. Statins are lipid-lowering drugs broadly used for dyslipidemia treatment but have also been reported to have several pleiotropic effects, including antimicrobial activity against fungi, parasites, and bacteria. In the present study, we tested the susceptibility of M. ulcerans to several statins, namely atorvastatin, simvastatin, lovastatin and fluvastatin. Using broth microdilution assays and cultures of M. ulcerans-infected macrophages, we found that atorvastatin, simvastatin and fluvastatin had antimicrobial activity against M. ulcerans. Furthermore, when using the in vitro checkerboard assay, the combinatory additive effect of atorvastatin and fluvastatin with the standard antibiotics used for Buruli Ulcer treatment highlighted the potential of statins as adjuvant drugs. In conclusion, statins hold promise as potential treatment options for Buruli Ulcer. Further studies are necessary to validate their effectiveness and understand the mechanism of action of statins against M. ulcerans.

Regina Elena Institute (R.E.I.) Protocol for Breast Implant Salvage: Preliminary Results

Introductionimplants are the most popular means of restoring the breast mound after mastectomy; the most feared complication is implant infection accounting for 4.8% to 35.4% of cases. Various antibiotic regimens or other surgical revisions to treat implant infections have been reported, but their failure rates are unacceptable. Implant removal is subsequently the most common recourse for managing prosthesis infections. we report preliminary results of infected breast implant salvage using our Regina Elena Institute (REI) protocol. MethodsSince June 2021, a prospective single-centre study has been ongoing for patients burdened by implant infection or exposure. All qualifying participants underwent our REI protocol. They receive a temporary smooth implant and 1 week of implant's pocket irrigation with antibiotic solution along with systemic antibiotic and then a new permanent prosthesis positioning. ResultsTen of whom completed at least 6 months of follow-up and were eligible for this preliminary analysis. Overall, the REI protocol was applied to 13 breasts. No infections relapsed during the 6-month minimum follow-up intervals; and no early capsular contraction was evident, resulting in good cosmetic outcomes for every treated breast. DiscussionThe smooth-surfaced implant's sizer helps maintain tissue expansion, preventing skin retraction; and the slightly smaller diameters used (compared with originals) facilitate antibiotic wash distribution. Combining a targeted systemic antibiotic and a topical agent is the best way to optimise infection resolution. This preliminary analysis has clear limitations. A larger population is warranted to increase the level of evidence. Longer follow-up is also advisable to monitor for delayed infection recurrence.

Nosocomial infections by diverse carbapenemase-producing Aeromonas hydrophila associated with combination of plumbing issues and heat waves

Aquatic opportunistic pathogen Aeromonas hydrophila, known to persist in low-nutrient chlorinated waters, can cause life-threatening infections. Two intensive care units experienced a cluster of Aeromonas infections following outdoor temperature spikes coinciding with recurrent plumbing issues, with fatalities due to severe underlying comorbidities co-occurring with extensively-drug resistant (XDR) Aeromonas. We investigated this cluster using whole genome sequencing to assess genetic relatedness of isolates and identify antimicrobial resistance determinants. Three A. hydrophila were isolated from patients staying in or adjacent to rooms with plumbing issues during or immediately after periods of elevated outdoor temperatures. Sinks and faucets were swabbed for culture. All A. hydrophila clinical isolates exhibited carbapenem resistance but were not genetically related. Diverse resistance determinants corresponding to extensively-drug resistant were found, including co-occurring KPC-3 and VIM-2, OXA-232, and chromosomal CphA-like carbapenemase genes, contributing to major treatment challenges. All 3 patients were treated with multiple antibiotic regimens to overcome various carbapenemase classes and expired due to underlying comorbidities. Environmental culture yielded no Aeromonas. While the investigation revealed no singular source of contamination, it supports a possible link between plumbing issues, elevated outdoor temperatures and incidence of nosocomial Aeromonas infections. The diversity of carbapenemase genes detected in these wastewater-derived Aeromonas warrants heightened infection prevention precautions during periods of plumbing problems especially with heat waves.

A rare case of periprosthetic joint infection of the hip due to Kocuria spp.

BackgroundKocuria spp. are ubiquitous bacteria that have gained recent attention as potential infectious agents. The most common bacteria in PJI are S. aureus und S. epidermidis.Case presentationWe present the case of a 72-year-old woman who received total hip arthroplasty after a traumatic medial femoral neck fracture. Postoperatively, due to the clinical presentation of periprosthetic joint infection (PJI) revision surgery was performed twice. The microbiological tissue samples were positive for Kocuria spp. Initially, this was considered contamination and the patient was treated with various antibiotic regimens as well as prednisolone due to the differential diagnosis of pyoderma gangraenosum. However, a specialized histopathology lab performed further testing which substantiated the suspicion of a rare case of PJI due to Kocuria spp.ConclusionsTo our knowledge, this is the first reported case of a PJI caused by Kocuria spp. Further clinical research is necessary to assess whether Kocuria spp. are an underestimated cause of PJI.

Empirical cefepime+vancomycin versus ceftazidime+vancomycin versus meropenem+vancomycin in the treatment of healthcare-associated meningitis: results of the multicenter Ephesus study

BackgroundHerein, we analyzed the efficacy of main antibiotic therapy regimens in the treatment of healthcare-associated meningitis (HCAM).Materials/methodsThis retrospective cohort study was conducted in 18 tertiary-care academic hospitals Turkey, India, Egypt and Romania. We extracted data and outcomes of all patients with post-neurosurgical meningitis cases fulfilling the study inclusion criteria and treated with empirical therapy between December 2006-September 2018.ResultsTwenty patients in the cefepime + vancomycin-(CV) group, 31 patients in the ceftazidime + vancomycin-(CFV) group, and 119 patients in the meropenem + vancomycin-(MV) group met the inclusion criteria. The MV subgroup had a significantly higher mean Glasgow Coma Score, a higher rate of admission to the intensive care unit within the previous month, and a higher rate of antibiot herapy within the previous month before the meningitis episode (p < 0.05). Microbiological success on Day 3–5, end of treatment (EOT) clinical success (80% vs. 54.8%% vs 57.9%), and overall success (EOT success followed by one-month survival without relapse or reinfection 65% vs. 51.6% vs. 45.3%), EOT all cause mortality (ACM) and day 30 ACM (15% vs. 22.6% vs. 26%) did not differ significantly (p > 0.05) among the three cohorts. No regimen was effective against carbapenem-resistant bacteria, and vancomycin resulted in an EOT clinical success rate of 60.6% in the methicillin-resistant staphylococci or ampicillin-resistant enterococci subgroup (n = 34).ConclusionsOur study showed no significant difference in terms of clinical success and mortality among the three treatment options. All regimens were ineffective against carbapenem-resistant bacteria. Vancomycin was unsuccessful in approximately 40% of cases involving methicillin-resistant staphylococci or ampicillin-resistant enterococci.

Uncovering a Rarely Diagnosed Disease: Severe Leptospirosis with Multiorgan Failure in Slovakia

Leptospirosis is a zoonotic disease caused by bacteria from the genus Leptospira. The infection occurs mainly in developing countries in the tropical zone and countries with lower hygiene standards. The highest incidence is observed especially in environments associated with the presence of rodents, mainly rats, which are a potential source of infection. The clinical manifestations and severity of leptospirosis are highly variable. This case report describes the a 53-year-old patient (male) without comorbidities, who was admitted to an infectious disease department in the east of Slovakia for jaundice, general fatigue, weakness, and fever (health difficulties for approximately 7 days at home). The clinical laboratory picture of the patient was dominated by significant hyperbilirubinemia, acute renal failure, hepatopathy, severe thrombocytopenia, and involvement of the lung parenchyma in the sense of bilateral interstitial pneumonia on chest X-ray. A double combination of antibiotics (ceftriaxone and clarithromycin) were added to the treatment. During hospitalization, a diagnosis of leptospirosis was suspected based on medical history and the results of laboratory tests and was subsequently confirmed serologically. The antibiotic regimen was de-escalated to cephalosporin (ceftriaxone) monotherapy with adequate laboratory and clinical effects (on the 4th day). The patient was discharged after a total of 18 days in good clinical condition.

A prospective randomized clinical trial to assess antibiotic pocket irrigation on tissue expander breast reconstruction.

Bacterial infection is the most common complication following staged post-mastectomy breast reconstruction initiated with a tissue expander (TE). To limit bacterial infection, antibiotic irrigation of the surgical site is commonly performed despite little high-quality data to support this practice. We performed a prospective randomized control trial to compare the impact of saline irrigation alone to a triple antibiotic irrigation regimen (1 g cefazolin, 80 mg gentamicin, and 50,000 units of bacitracin in 500 mL of saline) for breast implant surgery. The microbiome in breasts with cancer (n = 16) was compared to those without (n = 16), as all patients (n = 16) had unilateral cancers but bilateral mastectomies (n = 32). Biologic and prosthetic specimens procured both at the time of mastectomy and during TE removal months later were analyzed for longitudinal comparison. Outcomes included clinical infection, bacterial abundance, and relative microbiome composition. No patient in either group suffered a reconstructive failure or developed an infection. Triple antibiotic irrigation administered at the time of immediate TE reconstruction did not reduce bacterial abundance or impact microbial diversity relative to saline irrigation at the time of planned exchange. Implanted prosthetic material adopted the microbial composition of the surrounding host tissue. In cancer-naïve breasts, relative to saline, antibiotic irrigation increased bacterial abundance on periprosthetic capsules (P = 0.03) and acellular dermal matrices (P = 0.04) and altered the microbiota on both. These data show that, relative to saline only, the use of triple antibiotic irrigation in TE breast reconstruction does impact the bacterial abundance and diversity of certain biomaterials from cancer-naïve breasts. IMPORTANCE The lifetime risk of breast cancer is ~13% in women and is treated with a mastectomy in ~50% of cases. The majority are reconstructed, usually starting with a tissue expander to help restore the volume for a subsequent permanent breast implant or the women's own tissues. The biopsychosocial benefits of breast reconstruction, though, can be tempered by a high complication rate of at least 7% but over 30% in some women. Bacterial infection is the most common complication, and can lead to treatment delays, patient physical and emotional distress and escalating health care cost. To limit this risk, plastic surgeons have tried a variety of strategies to limit bacterial infection including irrigating the pocket created after removing the breast implant with antibiotic solutions, but good-quality data are scarce. Herein, we study the value of antibiotics in pocket irrigation using a robust randomized clinical trial design and molecular microbiology approaches.

RNA-based antibiotic susceptibility testing of tmexCD-toprJ-mediated tigecycline resistance in Klebsiella pneumoniae

The emergence and prevalence of plasmid-encoded RND-type efflux pump TMexCD-TOprJ severely compromise tigecycline treatment, which is recognized as the last resort for multidrug-resistant (MDR) Gram-negative bacterial infections. There is an urgent need for rapid antibiotic susceptibility testing (AST) that can simultaneously identify the genotype and phenotype of tmexCD-toprJ-positive bacteria. Through characterizing transcriptional profiling responses of tmexCD-toprJ-positive and -negative strains after exposure to 2 μg/mL tigecycline, here we identified 12 differentially RNA biomarkers and developed an RNA-based AST (RBAST) to distinguish tmexCD-toprJ-positive and -negative K. pneumoniae. These mRNA biomarkers were successfully validated in tigecycline exposure time variations, concentration shifts, and other tmexCD-toprJ variants. In addition, a group of clinical isolated strains was effectively distinguished using RBAST, with an accuracy of over 94% during 3 h test period. Our work highlights the potential of RNA transcripts as biomarkers for rapid AST, which will contribute to deploying effective antibiotic regimens in clinical practice.

Colon Injuries and Infectious Complications in Concurrent Gunshot-Related Fractures

IntroductionConcurrent colonic injury among patients with gunshot-related fractures presents a potential risk for infectious complications. We hypothesized that colon injuries are associated with more infectious orthopedic complications among gunshot victims with concurrent fractures. Materials and methodsWe reviewed trauma patients arriving at our level 1 trauma center from January 1, 2019 to May 31, 2022 who suffered any gunshot-related fracture and also underwent an exploratory laparotomy. Of these patients, those with colon injuries were compared to those without colon injuries. Baseline characteristics, including antibiotic regimens, were collected in addition to outcomes of length of stay, intensive care unit admission, ventilator requirement, and development of infectious orthopedic complications. ResultsOverall, 56 of the 107 included patients had colon injuries. Age, sex, race/ethnicity, and Injury Severity Score were similar between groups. Of patients with colonic injuries, 16.1% received early, repeat dosing of broad-spectrum antibiotics, while only 3.9% of patients without colonic injuries received this antibiotic dosing (P = 0.04). Interestingly, only patients with colon injuries developed infectious orthopedic complications and none of the patients without colon injuries developed such complications (10.7% versus 0.0%, P = 0.03). All patients with orthopedic infections had infected pelvic fractures. Length of stay was 3 d longer in the colon injury group (P = 0.04). There was no difference in intensive care unit admission, ventilator requirement, or death. ConclusionsConcurrent colon injuries among patients with gunshot-related fractures are associated with higher risk of infectious orthopedic complications, likely from direct spread of fecal contaminant. Early, broad-spectrum antibiotics may be associated with reduced infectious orthopedic complications.

Trimethoprim-Sulfamethoxazole for Pediatric Osteoarticular Infections.

Trimethoprim-sulfamethoxazole (TMP-SMX) is active against most Staphylococcus aureus isolates but is not widely used for treatment of pediatric osteoarticular infections. This was a comparative effectiveness study of hospitalized patients ≤18 years treated with TMP-SMX versus other antibiotic regimens for acute osteoarticular infections between 2016 and 2021 at three hospitals using inverse probability of treatment weighted propensity score analysis. The primary outcome was treatment failure, a composite of unanticipated emergency department (ED) or outpatient visits, hospital readmissions, extension or change of antibiotic therapy due to inadequate clinical response, or death, all within 6 months after completing antibiotics. The secondary outcome was antibiotic-associated adverse events (AEs) within 6 months. The exposed group for the treatment failure analysis included children who received ≥7 days of TMP-SMX and did not experience treatment failure while on another antibiotic. Children receiving at least one dose of TMP-SMX were the exposed group for the AE analysis. 116 patients met eligibility criteria; 26 (22.4%) patients were classified into the TMP-SMX cohort and 90 (77.6%) into the other antibiotics cohort (most commonly clindamycin, vancomycin, and cefazolin). There was no significant difference in treatment failure between TMP-SMX and other antibiotics (43% vs 19%; 95% CI 0.9-10.4). More patients in the TMP-SMX cohort experienced an unplanned ED or outpatient visit (OR 4.8, 95% CI 1.3-17.8). There was no difference in hospital readmission, antibiotic change, or duration extension. Exposure to TMP-SMX was associated with more AEs (41% vs 19%, p=0.012). Treatment with TMP-SMX was not associated with greater clinical failure but was associated with more AEs compared to alternative agents for the treatment of pediatric acute osteoarticular infections.

Antibiotic prophylaxis and surgical site infections in orthognathic surgery – a retrospective analysis

BackgroundThis study was conducted to determine surgical site infection (SSI) rates and potential risk factors as well as to evaluate antibiotic prophylaxis in orthognathic surgery.MethodsThis retrospective observational study included patients who received orthognathic surgery. SSIs and their management were assessed for up to one year post-operatively. The applied antibiotic regime and other possible influencing factors (smoking, age, site of infection, drainage, duration of surgery, displacement distances, craniofacial malformations) were assessed.ResultsIn total 291 patient met the inclusion criteria (56.7% female). The mean age at surgery was 25.5 ± 8.5 years. Fifty-four patients (18.6%) were diagnosed with a craniofacial malformation. Relevant previous surgeries were documented in about one quarter of included patients (n = 75). Ninety-two percent of patients (n = 267) received intraoperative single-dose antibiotic prophylaxis. Surgical site infections occurred in 12.4% (n = 36) of patients. There was a significant association between postoperative infections and type of surgery (P = .037) as well as type of drainage (P = .002). Statistical analyses also revealed a higher prevalence of smokers (P = .036) and previous surgically assisted rapid palatal expansion (SARPE) (P = .018) in the infection group. Furthermore, no significant relationships were observed between postoperative infections and various co-factors (i.e. antibiotic regime, age at surgery, gender, associated craniofacial malformations, surgery duration, displacement distances, mandibular setback vs. advancement).ConclusionLow rates of SSIs occurred following an intraoperative single-dose antibiotic regime. None of the SSIs had a significant effect on the final surgical outcome. Present data do not warrant escalation of the antibiotic regimen. Postoperative smoking and capillary drainage should be avoided.

46 Association of Empiric Antibiotic Selection on Clinical Outcomes in Hospitalized Children with Severe Orbital Infections: A Multicenter Cohort Study

Abstract Background Antibiotic selection in children with periorbital and orbital infections is often empiric and regimens vary widely among institutions in their spectrum and inclusion of anti-anaerobic and anti-staphylococcal agents. Objectives Currently, there are no national clinical guidelines for antibiotic selection and no studies comparing commonly used antibiotic regimens in orbital infections. We aimed to determine the association of initial empiric antibiotic regimens with clinical outcomes in children hospitalized with severe orbital infections. Design/Methods We conducted a multicentre cohort study of children with severe orbital infections admitted to ten hospitals between January 1, 2009, and December 31, 2018. The association between empiric antibiotic regimen in the first 24 hours of hospitalization with length of stay and surgical intervention were assessed with multivariable median regression and multivariate logistic regression, respectively. Results Of 1421 patients, 60.0% were male, and mean age was 6.4 years (SD 4.5). Median length of stay was 86.4 hours (IQR 56.9-137.5) and 180 (12.7%) received surgical intervention. The most frequently (23.6%) administered empiric regimen consisted of a third-generation cephalosporin, anaerobic agent, and staphylococcal agent. After adjustment, broad-spectrum empiric antibiotic regimens with dedicated anti-anaerobic and/or staphylococcal coverage were associated with increased length of stay, ranging from an additional 18.4 hours (95% CI, 6.82, 30.0) to 21.5 hours (95% CI, 11.0, 32.0). Only patients with staphylococcal coverage alone had a statistically significant increased odds of surgical intervention (4.45, 95% CI 1.03, 19.2). Conclusion In children hospitalized with severe orbital infections, broad-spectrum therapy with or without coverage for staphylococci and anaerobes were associated with similar clinical outcomes in a clinical setting with low methicillin-resistant Staphylococcus aureus prevalence. Clinical practice guidelines are needed to standardize antibiotic recommendations.

Assessment of Bacterial Infections and Antibiotic Regimens in Intravenous Drug Users.

Bacterial infections in people who inject drugs (PWID) are a significant cause of hospitalizations and increased morbidity in this group. In this review, we evaluated bacterial trends in the most common infections and appropriate empiric antibiotic coverage. Articles from PubMed and Google Scholar were curated in a Google document with shared access. Discussion and development of the paper were achieved over Zoom meetings.The common infections in PWID were skin and soft tissue infections (SSTIs), infective endocarditis, septic arthritis, osteomyelitis, and bloodstream infections (BSIs). The presence of comorbidities increased susceptibility to bacterial infections. Staphylococcus aureus was the predominant species in all the infections and included methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). The current standard of antibiotic use for Staphylococcus species was found to be sufficient. The gram-negative bacillus Serratia marcescens was prevalent in PWID as a causative agent of septic arthritis, osteomyelitis, and infective endocarditis. Its treatment required a combination of β-lactam and either a fluoroquinolone or an aminoglycoside for a prolonged duration. Streptococci were commonly implicated in SSTIs and BSIs. The appropriate response was seen with β-lactam antibiotics. In PWID, Enterococcus and Pseudomonas were implicated in infective endocarditis of native and prosthetic valves. The former being difficult to treat, a new strategy of using dual β-lactam antibiotics was found to be supported by clinical data. Anti-pseudomonal antibiotics can be avoided in other infections seen in this group, as their prevalence was low. PWID, especially those with comorbidities, have an increased risk of acquiring infections with difficult-to-treat microbes. Therefore, empiric antibiotic treatment should be relevant to the infection, for which bacterial trends and antibiotic susceptibility must be reassessed periodically.

Switching from intravenous vancomycin to oral antibiotics reduces adverse events in a retrospective cohort of outpatients with orthopedic infections.

Vancomycin is frequently used for prolonged courses in treating osteoarticular infections despite a high rate of adverse drug events (ADE). The objective of this study was to evaluate the safety and effectiveness of transitioning to oral therapy compared to continuing parenteral vancomycin in patients with orthopedic infections. We conducted a single-center, retrospective cohort study of patients with orthopedic infections discharged on parenteral vancomycin with a planned duration of at least four weeks. We compared rates of ADE while on vancomycin to rates of ADE after switching to an oral regimen. As a secondary analysis, we compared unplanned hospital readmission within 60 days and treatment failure at one year between patients who were transitioned to oral antibiotics within four weeks of vancomycin initiation and those that were not. Two hundred twenty-eight patients met inclusion criteria. Vancomycin was associated with significantly greater toxicity compared to oral regimens. Fifty-one patients had an adverse event while on vancomycin (5.87 ADE per 1000 patient-days) while 9 patients had an adverse event on oral therapy (1.49 ADE per 1000 patient-days) (Rate difference 4.39 per 1000 patient days, 95% CI: 2.52 to 6.26 events per 1000 patient-days). In proportional hazards analysis, transition to an oral antibiotic regimen was independently associated with a lower rate of ADE (aHR 0.12, 95% CI: 0.02-0.86). Forty-one patients (18%) were transitioned to oral therapy within four weeks; these patients did not have an increased rate of unplanned readmission (12.2% vs 17.1%) or treatment failure (17.1% vs 21.9%). Patients transitioned to oral therapy within 4 weeks of discharge had significantly fewer adverse events and similar incidences of one-year treatment failure compared to patients maintained on parenteral vancomycin. Substituting oral antibiotics for parenteral vancomycin is a potential strategy to minimize vancomycin toxicity during the treatment of orthopedic infections.