"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.

Extrapulmonary, Chronic Septic Arthritis From Mycobacterium tuberculosis in the Ankle and Subtalar Joints.

In the United States, rates of Mycobacterium tuberculosis infection have been declining for decades. Osteoarticular tuberculosis of the ankle is rarely observed. We present the case of a 65-year-old man who immigrated to the United States from India 24 years before the onset of symptoms. The patient initially reported atraumatic swelling and pain of the left ankle and foot and was treated for venous insufficiency. Later, the patient was referred to a nonsurgical orthopaedic clinic for additional workup and was found to have elevated inflammatory markers. MRI showed septic arthritis and osteomyelitis of the talus, distal tibia, and calcaneus. Joint aspiration revealed elevated white blood cell counts with predominately PMNs. The patient was then referred to an orthopaedic foot and ankle surgeon and underwent extensive irrigation and débridement. The patient was discharged on empiric antibiotics. Culture results from the original joint aspirate returned 14 days after surgery as positive for acid-fast bacillus, later identified as M tuberculosis by sequencing. Empiric antibiotics were discontinued, and the patient was started on appropriate antituberculotic therapy. This case report illustrates the challenge in the diagnosis of skeletal tuberculosis and the importance of including this condition on the differential for patients with atypical foot and ankle presentations.

How We Approach Suppressive Antibiotic Therapy Following Debridement, Antibiotics, and Implant Retention for Prosthetic Joint Infection.

The optimal treatment of prosthetic joint infection (PJI) remains uncertain. Patients undergoing debridement, antibiotics, and implant retention (DAIR) receive extended antimicrobial treatment, and some experts leave patients at perceived highest risk of relapse on suppressive antibiotic therapy (SAT). In this narrative review, we synthesize the literature concerning the role of SAT to prevent treatment failure following DAIR, attempting to answer 3 key questions: (1) What factors identify patients at highest risk for treatment failure after DAIR (ie, patients with the greatest potential to benefit from SAT), (2) Does SAT reduce the rate of treatment failure after DAIR, and (3) What are the rates of treatment failure and adverse events necessitating treatment discontinuation in patients receiving SAT? We conclude by proposing risk-benefit stratification criteria to guide use of SAT after DAIR for PJI, informed by the limited available literature.

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.

Mycetomalike Skin Infection Due to Gordonia bronchialis in an Immunocompetent Patient.

Gordonia bronchialis is a partially acid-fast, gram-positive rod that has been found in a variety of nosocomial infections, most frequently sternal wound infection following coronary artery bypass surgery. We report a case of a mycetomalike infection due to G bronchialis in an immunocompetent patient with complete resolution after 3 months of oral antibiotics.

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.

The intersection of fracture healing and infection: Orthopaedics research society workshop 2021.

Infection is a common cause of impaired fracture healing. In the clinical setting, definitive fracture treatment and infection are often treated separately and sequentially, by different clinical specialties. The ability to treat infection while promoting fracture healing will greatly reduce the cost, number of procedures, and patient morbidity associated with infected fractures. In order to develop new therapies, scientists and engineers must understand the clinical need, current standards of care, pathologic effects of infection on fractures, available preclinical models, and novel technologies. One of the main causes of poor fracture healing is infection; unfortunately, bone regeneration and infection research are typically approached independently and viewed as two separate disciplines. Here, we aim to bring these two groups together in an educational workshop to promote research into the basic and translational science that will address the clinical challenge of delayed fracture healing due to infection. Statement of clinical significance: Infection and nonunion are each feared outcomes in fracture care, and infection is a significant driver of nonunion. The impact of nonunions on patie[Q2]nt well-being is substantial. Outcome data suggests a long bone nonunion is as impactful on health-related quality of life measures as a diagnosis of type 1 diabetes and fracture-related infection has been shown to significantly l[Q3]ower a patient's quality of life for over 4 years.  Although they frequently are associated with one another, the treatment approaches for infections and nonunions are not always complimentary and cannot be performed simultaneously without accepting tradeoffs. Furthermore, different clinical specialties are often required to address the problem, the orthopedic surgeon treating the fracture and an infectious disease specialist addressing the sources of infection. A sequential approach that optimizes treatment parameters requires more time, more surgeries, and thus confers increased morbidity to the patient. The ability to solve fracture healing and infection clearance simultaneously in a contaminated defect would benefit both the patient and the health care system.

Validation of a Community-Acquired Pneumonia Score To Improve Empiric Antibiotic Selection at an Academic Medical Center.

The 2019 American Thoracic Society and the Infectious Diseases Society of America community-acquired pneumonia (CAP) guidelines recommend that drug-resistant pathogens (DRP) be empirically covered if locally validated risk factors are present. This retrospective case-control validation study evaluated the performance of the drug resistance in pneumonia (DRIP) clinical prediction score. Two hundred seventeen adult patients with ICD-10 (https://www.who.int/classifications/classification-of-diseases) pneumonia diagnosis, positive confirmed microbiologic data, and clinical signs and symptoms were included. A DRIP score of ≥4 was used to assess model performance. Logistic regression was used to select for significant predictors and create a modified DRIP score, which was evaluated to define clinical application. The DRIP score predicted pneumonia due to a DRP with a sensitivity of 67% and specificity of 73%. The area under the receiver operating characteristic (AUROC) curve was 0.76 (95% confidence interval [CI], 0.69 to 0.82). From regression analysis, prior infection with a DRP and antibiotics in the last 60 days, yielding scores of 2 points and 1 point, respectively, remained local risk factors in predicting drug-resistant pneumonia. Sensitivity (47%) and specificity (94%) were maximized at a threshold of ≥2 in the modified DRIP model. Therefore, prior infection with a DRP remained the only clinically relevant predictor for drug-resistant pneumonia. The original DRIP score demonstrated a decreased performance in our patient population and behaved similarly to other clinical prediction models. Empiric CAP therapy without anti-methicillin-resistant Staphylococcus aureus and antipseudomonal coverage should be considered for noncritically ill patients without a drug resistant pathogen infection in the past year. Our data support the necessity of local validation to authenticate clinical risk predictors for drug-resistant pneumonia.

Clinical Experience With a Coordinated Multidisciplinary Approach to Treating Prosthetic Joint Infection.

The successful treatment of prosthetic joint infection (PJI) is difficult, requiring coordination across multiple specialties. In 2017, we formed a collaboration between our infectious disease clinicians and our orthopaedic arthroplasty surgeons in an effort to optimize care, accommodate patients, and expedite clinical decision-making in the treatment of PJI. The model consisted of combined infectious disease and arthroplasty clinics, standardized lab results, and planned staged revision procedures. We named this the arthroplasty infection service. Our early experience with a defined multidisciplinary approach to PJI was positive. Although the impact of the arthroplasty infection service on PJI outcomes is yet to be determined, we believe this is a step forward in the management of this complex patient population. With an increasing burden of PJI in the United States, this model could be emulated at many institutions that regularly treat these challenging cases.

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.

The role of procalcitonin in respiratory infections.

Accurate diagnosis, risk stratification, and decisions about the need for and optimal duration of antibiotic therapy are cornerstones of the management of patients with respiratory infections. A growing body of evidence supports the use of procalcitonin, a marker of bacterial infection, in addition to conventional clinical parameters to improve diagnostic and prognostic assessment in patients with suspicion of respiratory infections. In addition, several randomized controlled trials indicate that procalcitonin may be used for clinical decision making about initiation and optimal duration of antibiotic therapy. For patients with respiratory infections, procalcitonin-guided antibiotic therapy resulted in less antibiotic use without any apparent adverse patient outcome. For other infections outcome studies are currently lacking. This review summarizes the results of recent investigations of procalcitonin in respiratory infections to provide physicians an overview of the utility and limitations of procalcitonin when used for bedside decision making.