"Once more, with feeling": no difference in outcomes between patients discharged on oral versus intravenous antibiotics for orthopedic infections in a propensity score matched cohort at a US medical center.

Objective: To compare outcomes between patients discharged on intravenous (IV) versus oral (PO) antibiotics for the treatment of orthopedic infections, after creation of an IV-to-PO guideline, at a single academic medical center in the United States. Methods: This was a retrospective, propensity score matched, cohort study of adult patients hospitalized for orthopedic infections from September 30, 2020, to April 30, 2022. Patients discharged on PO antibiotics were matched to patients discharged on IV antibiotics. The primary outcome was one-year treatment failure following discharge. Secondary outcomes were incidence of 60-day treatment failure, adverse drug events (ADE), readmissions, infectious disease clinic "no-show" rates, and emergency department (ED) encounters. Results: Ninety PO-treated patients were matched to 90 IV-treated patients. Baseline characteristics were similar in the two groups after matching. There was no significant difference in the proportions of patients on PO versus IV antibiotics experiencing treatment failure at one year (26% vs 31%, P = .47). There were no significant differences for any secondary outcomes: treatment failure within 60 days (13% vs 14%, P = 1.00), ADE (13% vs 11%, P = .82), unplanned readmission (17% vs 21%, P = .57), or ED encounters (9% vs 18%, P = .54). Survival analyses identified no significant differences in time-to-event between PO and IV treatment for any of the outcomes assessed. Conclusions: There were no appreciable differences in outcomes between patients discharged on PO compared to IV regimens. Antimicrobial stewardship interventions to increase prescribing of PO antibiotics for the treatment of orthopedic infections should be encouraged.

Similar Efficacy and Lower Cost Associated With Ceftazidime Compared to Tobramycin Coupled With Vancomycin in Antibiotic Spacers in the Treatment of Periprosthetic Joint Infection.

BACKGROUND: Vancomycin and tobramycin have traditionally been used in antibiotic spacers. In 2020, our institution replaced tobramycin with ceftazidime. We hypothesized that the use of ceftazidime/vancomycin (CV) in antibiotic spacers would not lead to an increase in treatment failure compared to tobramycin/vancomycin (TV). METHODS: From 2014 to 2022, we identified 243 patients who underwent a stage I revision for periprosthetic joint infection. The primary outcome was a recurrent infection requiring antibiotic spacer exchange. We were adequately powered to detect a 10% difference in recurrent infection. Patients who had a prior failed stage I or two-stage revision for infection, acute kidney injury prior to surgery, or end-stage renal disease were excluded. Given no other changes to our spacer constructs, we estimated cost differences attributable to the antibiotic change. Chi-square and t-tests were used to compare the two groups. Multivariable logistic regressions were utilized for the outcomes. RESULTS: The combination of TV was used in 127 patients; CV was used in 116 patients. Within one year of stage I, 9.8% of the TV group had a recurrence of infection versus 7.8% of the CV group (P = .60). By final follow-up, results were similar (12.6 versus 8.6%, respectively, P = .32). Adjusting for potential risk factors did not alter the results. Cost savings for ceftazidime versus tobramycin are estimated to be $68,550 per one hundred patients treated. CONCLUSIONS: Replacing tobramycin with ceftazidime in antibiotic spacers yielded similar periprosthetic joint infection eradication success at a lower cost. While larger studies are warranted to confirm these efficacy and cost-saving results, our data justifies the continued investigation and use of ceftazidime as an alternative to tobramycin in antibiotic spacers.

Genomic Characterization of 2 Cutibacterium acnes Isolates from a Surgical Site Infection Reveals Large Genomic Inversion.

Background: Cutibacterium acnes is a common commensal of human skin but may also present as an opportunistic pathogen in prosthetic joint and wound infections. Unfortunately, few complete genomes of C. acnes are publicly available, and even fewer are of isolates associated with infection. Here we report the isolation, characterization, and complete genomes of 2 C. acnes isolates from a surgical site infection of an elbow. Methods: We used standard microbiological methods for phenotypic characterization and performed whole genome sequencing on 2 C. acnes isolates using a combination of short-read and long-read sequencing. Results: Antibiotic susceptibility testing showed beta-lactamase negative and low minimal inhibitory concentrations to all antibiotics tested, with the exception of metronidazole. We assembled complete genomes of the 2 isolates, which are approximately 2.5 megabases in length. The isolates belong to the single-locus sequence type (SLST) H1 and the multi-locus sequence type (MLST) IB. Both isolates have similar composition of known virulence genes, and we found no evidence of plasmids but did find phage-associated genes. Notably, the 2 genomes are 99.97% identical but contain a large genomic inversion encompassing approximately half of the genome. Conclusions: This is the first characterization of this large-scale genomic inversion in nearly identical isolates from the same wound. This report adds to the limited numbers of publicly available infection-associated complete genomes of C. acnes.

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

INTRODUCTION: 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. METHODS: We conducted a single-center, retrospective cohort study of patients with orthopedic infections discharged on parenteral vancomycin with a planned duration of at least 4 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 1 year between patients who were transitioned to oral antibiotics within 4 weeks of vancomycin initiation and those that were not. RESULTS: Two hundred twenty-eight patients met the 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 4 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%). CONCLUSIONS: Patients transitioned to oral therapy within 4 weeks of discharge had significantly fewer adverse events and similar incidences of 1-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.

Association of Acute Kidney Injury With Antibiotic Loaded Cement Used for Treatment of Periprosthetic Joint Infection.

BACKGROUND: Antibiotic-loaded bone cement (ALBC) is commonly used in the treatment of periprosthetic joint infections (PJIs) to increase the local concentration of antibiotic at the site of infection. Use of ALBC has been associated with rare instances of acute kidney injury (AKI) despite low systemic absorption of the nephrotoxic antibiotics; however, the incidence of AKI is unknown. The purpose of this study was to determine the incidence of and risk factors for AKI associated with ALBC. METHODS: This single-site, retrospective cohort study compared 162 PJI patients who underwent Stage 1 revision to a spacer with ALBC to 115 PJI patients who underwent debridement, antibiotics, and implant retention (DAIR) without the use of ALBC. Both groups received similar systemic antibiotics postoperatively. Descriptive statistics and multivariable logistic regressions were used to analyze risk factors for AKI. RESULTS: There was no statistically significant difference in the rate of AKI: 29 patients (17.9%) in the ALBC group and 17 (14.7%) in DAIR group developed AKI (odds ratio 1.43; 95% CI 0.70 to 2.93). There was a trend toward increased severity of AKI in the ALBC group. Chronic kidney disease, systemic vancomycin, and diuretic use were independent factors associated with the risk of AKI. CONCLUSION: An AKI occurred in 17% of PJI patients receiving either a spacer with ALBC or a DAIR. The use of ALBC was not associated with a significant increased risk of AKI. However, the use of systemic vancomycin and diuretic use were independent predictors of AKI in this patient population.

Patient safety outcomes for continuous infusion vancomycin as outpatient parenteral antimicrobial therapy.

BACKGROUND: Administration of vancomycin as a continuous infusion has been associated with reduced nephrotoxicity. Given limited published experience with continuous infusion vancomycin in outpatient parenteral antimicrobial therapy (OPAT) programs, we reviewed outcomes from our center. METHODS: This was a retrospective, single-center study of adult patients receiving vancomycin OPAT as continuous or intermittent infusion for an intended treatment duration of at least 7 days. The primary outcome was time to nephrotoxicity with continuous versus intermittent infusion vancomycin while on OPAT; additional outcomes included time to any vancomycin-associated adverse event, time to 60-day death or readmission, and time to 60-day emergency department encounter. Proportional hazards modeling was used to identify variables independently associated with outcomes, as well as assess the strength of association of continuous infusion with each outcome. RESULTS: Four-hundred ninety-two patients were included: 118 treated with continuous and 374 with intermittent vancomycin infusion. Continuous infusion was not associated with lower rates of nephrotoxicity compared to intermittent infusion (adjusted hazard ratio (aHR) 0.72, 95% CI: 0.35-1.50). There were no advantages of continuous over intermittent infusion in the rates of any adverse event (aHR 0.93, 95% CI: 0.56-1.53), 60-day death or readmission (aHR 1.04, 95% CI: 0.68-1.61), or 60-day emergency department encounter (aHR 1.17, 95% CI: 0.68-1.99). Vancomycin area under the concentration-time curve (AUC) at discharge was the only modifiable factor identified that was independently associated with patient safety outcomes. CONCLUSION: There was no appreciable benefit of continuous infusion vancomycin on outpatient safety outcomes. AUC-centered dosing approaches warrant further investigation as strategies to improve vancomycin safety in OPAT programs.

A Quality Initiative to Improve Postdischarge Care for Patients on Outpatient Parenteral Antimicrobial Therapy.

Background: Patients discharged from the hospital on outpatient parenteral antimicrobial therapy (OPAT) require close monitoring, including weekly blood tests and an early posthospital follow-up visit. However, because patients often receive OPAT in a separate healthcare system from where they received inpatient care, the OPAT plan often fails, with less than 75% of OPAT patients receiving the recommended laboratory monitoring. We sought to determine whether changing our inpatient OPAT documentation method would improve postdischarge care. Methods: As a quality improvement initiative, we conducted 2 Plan-Do-Study-Act interventions on our OPAT documentation. Our first intervention was to create a standardized OPAT Progress Note, and our second was to turn that note into a SmartForm (Epic) with discrete fields for the key information. We examined the effects of these changes on the rate of completion of recommended laboratory monitoring, attendance at outpatient follow-up visits, and 30-day readmission rates. Results: Changing our documentation to a standardized Progress Note and then to a SmartForm with discrete fields led to an increase in the proportion of patients with a serum creatinine checked within 10 days of discharge (from 63% to 71% to 73%) and who attended an infectious disease clinic visit within 3 weeks of discharge (from 21% to 36% to 47%). However, the rate of readmissions for OPAT-related problems did not change, nor did a composite outcome of 30-day mortality/unplanned readmission. Conclusions: Changes in how and where care plans are documented in the inpatient medical record can have significant effects on patient care outcomes after discharge.

Extended Oral Antibiotics Increase Bacterial Resistance in Patients Who Fail 2-Stage Exchange for Periprosthetic Joint Infection.

BACKGROUND: Although studies have demonstrated reductions in recurrent periprosthetic joint infection (PJI) with the administration of prolonged oral antibiotics at second-stage reimplantation, the potential for increasing bacterial resistance has not been studied. The purpose of this study was to determine if oral antibiotics at second-stage reimplantation increased the rate of antibiotic resistance in subsequent infections. METHODS: We retrospectively reviewed patients who underwent 2-stage exchange for chronic PJI from 2014 to 2019. We compared those who had received prolonged oral antibiotics at the time of stage 2 reimplantation with those who did not. The primary outcome was the presence of resistant organisms in any subsequent infection. The secondary outcome was the overall rate of recurrent PJI in the 2 groups. Multivariable analyses controlling for demographics and comorbid conditions were used. RESULTS: Of the 211 patients who underwent 2-stage exchange for PJI, 158 patients received prolonged oral antibiotics. The mean follow-up was 2.2 years. Recurrent PJI was diagnosed in 24 of 158 (15%) patients who received oral antibiotics compared with 11 of 53 (21%) patients who did not receive antibiotics (P = .35). PJI with resistant organisms was identified in 16 of 24 (67%) patients who received antibiotics compared with 0 of 11 (0%) patients who did not receive antibiotics (P = .0001). CONCLUSIONS: Prolonged oral antibiotics following 2-stage exchange increase drug resistance to that antibiotic in subsequent PJI. We recommend further research in the area to refine antimicrobial protocols as we consider the risks and benefits of prolonged antibiotic treatment.

Using Engineered Bacteria to Characterize Infection Dynamics and Antibiotic Effects In Vivo.

Synthetic biology has focused on engineering microbes to synthesize useful products or to serve as living diagnostics and therapeutics. Here we utilize a host-derived Escherichia coli strain engineered with a genetic toggle switch as a research tool to examine in vivo replicative states in a mouse model of chronic infection, and to compare in vivo and in vitro bacterial behavior. In contrast to the effect of antibiotics in vitro, we find that the fraction of actively dividing bacteria remains relatively high throughout the course of a chronic infection in vivo and increases in response to antibiotics. Moreover, the presence of non-dividing bacteria in vivo does not necessarily lead to an antibiotic-tolerant infection, in contrast to expectations from in vitro experiments. These results demonstrate the utility of engineered bacteria for querying pathogen behavior in vivo, and the importance of validating in vitro studies of antibiotic effects with in vivo models.

Effective multilevel teaching techniques on attending rounds: a pilot survey and systematic review of the literature.

BACKGROUND: While numerous authors acknowledge the challenge of teaching simultaneously to medical students, interns, and residents, few offer specific advice on how to meet that challenge, and none have studied which techniques are most effective. AIMS: The purpose of this study was to determine whether multilevel teaching is challenging for attendings, whether trainees feel that teaching on rounds is appropriate to their level, and to define multilevel teaching techniques. METHODS: We surveyed attendings and trainees on the internal medicine services at two academic medical centers. RESULTS: Attendings were divided about whether teaching to multiple levels posed a challenge. Trainees reported that the teaching they received was usually appropriate to their level of training. The most effective techniques for multilevel teaching were Broadening (asking "what if" questions), Targeting (directing questions at specific team members), and Novelty (teaching newly published information), while the least effective were techniques that taught advanced material unfamiliar to most or all of the team. A systematic literature review yielded no studies that focused on multilevel teaching techniques. CONCLUSIONS: This article is the first to define and evaluate specific techniques for multilevel instruction in a medical setting and identifies certain techniques as more effective at engaging multiple levels of learners simultaneously.

Characteristics of Plasmodium falciparum dhfr haplotypes that confer pyrimethamine resistance, Kilifi, Kenya, 1987--2006.

Resistance to the antimalarial drug sulfadoxine-pyrimethamine (SP) emerged in Plasmodium falciparum from Asia in the 1960s and subsequently spread to Africa. It is not known whether alleles that confer SP resistance also arose independently in Africa. We defined the coding region and microsatellite haplotypes of dhfr alleles in P. falciparum collected in Kilifi, Kenya, during 1987--2006, which spans the period when SP was first introduced. Isolates that carried a double-mutant or triple-mutant dhfr allele were detected at a low frequency, even during 1987--1988. Each of 2 double mutants carried a unique haplotype, and both were related to wild-type haplotypes from the same population. The number of isolates that carried a triple-mutant dhfr allele increased rapidly after introduction of SP and shared the haplotype of the triple mutant derived form Asia. We observed no triple-mutant alleles with haplotypes related to those of the Africa-derived wild-type and double-mutant alleles.

Plasmodium falciparum: a novel method for analyzing haplotypes in mixed infections.

Studying the population genetics of Plasmodium falciparum is necessary for understanding the spread of drug resistance. However, these studies are hampered by the inability to determine haplotypes from patient samples that contain multiple parasite populations. Therefore, we have developed a method for separating for genetic analysis the individual strains in a mixed infection. We amplified a 6 kb region of chromosome 4, including the dihydrofolate reductase gene and upstream microsatellite markers. This PCR product was inserted by recombination into a gapped yeast shuttle plasmid containing both selectable and counter-selectable markers. Because each plasmid contains only one insert and each yeast colony contains only one plasmid, the individual strains are now separate. We analyzed mixtures of 3D7, K1, and Dd2 DNA and correctly identified a haplotype in each case.

Prevalence, correlates, and trajectory of television viewing among infants and toddlers.

OBJECTIVES: Recognizing the negative effects of television on children, the American Academy of Pediatrics (AAP) recommends that children 2 years and older watch <2 hours of television per day and that children younger than 2 years watch no television. However, relatively little is known about the amount of television viewed by infants and toddlers. The objective of this study was to describe the prevalence and correlates of television viewing that exceeds the AAP guidelines for 0- to 35-month-olds and to examine the trajectory of a child's viewing over time. METHODS: Data from the National Longitudinal Survey of Youth, 1990 to 1998, were used to analyze reported television viewing at 0 to 35 months of age and to follow the trajectory of a child's viewing from infancy through age 6. Logistic regression models were used to determine risk factors associated with greater television viewing at 0 to 35 months and the association of early viewing habits with school-age viewing. RESULTS: Seventeen percent of 0- to 11-month-olds, 48% of 12- to 23-month-olds, and 41% of 24- to 35-month-olds were reported to watch more television than the AAP recommends. Compared with college graduates, less-educated women were more likely to report that their children watched more television than recommended. Children who watched >2 hours per day at age 2 were more likely to watch >2 hours per day at age 6 (odds ratio: 2.7; 95% confidence interval: 1.8-3.9), controlling for maternal education, race, marital status and employment, household income, and birth order. CONCLUSIONS: A substantial number of children begin watching television at an earlier age and in greater amounts than the AAP recommends. Furthermore, these early viewing patterns persist into childhood. Preventive intervention research on television viewing should consider targeting infants and toddlers and their families.