Impact of Mandatory Infectious Disease Specialist Approval on Hospital-Onset Clostridioides difficile Infection Rates and Testing Appropriateness.

BACKGROUND: Inappropriate Clostridioides difficile testing is common in the hospital setting, leading to potential overdiagnosis of infection when single-step nucleic acid amplification testing is used. The potential role of infectious diseases (ID) specialists in enforcing appropriate C. difficile testing is unclear. METHODS: At a single 697-bed academic hospital, we performed a retrospective study from 1 March 2012 to 31 December 2019 comparing hospital-onset C. difficile infection (HO-CDI) rates during 3 consecutive time periods: baseline 1 (37 months, no decision support), baseline 2 (32 months, computer decision support), and intervention period (25 months, mandatory ID specialist approval for all C. difficile testing on hospital day 4 or later). We used a discontinuous growth model to assess the impact of the intervention on HO-CDI rates. RESULTS: During the study period, we evaluated C. difficile infections across 331 180 admission and 1 172 015 patient-days. During the intervention period, a median of 1 HO-CDI test approval request per day (range, 0-6 alerts/day) was observed; adherence by providers with obtaining approval was 85%. The HO-CDI rate was 10.2, 10.4, and 4.3 events per 10 000 patient-days for each consecutive time period, respectively. In adjusted analysis, the HO-CDI rate did not differ significantly between the 2 baseline periods (P = .14) but did differ between the baseline 2 period and intervention period (P < .001). CONCLUSIONS: An ID-led C. difficile testing approval process was feasible and was associated with a >50% decrease in HO-CDI rates, due to enforcement of appropriate testing.

Prevalence of a Cefazolin Inoculum Effect Associated with blaZ Gene Types among Methicillin-Susceptible Staphylococcus aureus Isolates from Four Major Medical Centers in Chicago.

The efficacy of cefazolin with high-inoculum methicillin-susceptible Staphylococcus aureus (MSSA) infections remains in question due to therapeutic failure inferred as being due to an inoculum effect (InE). This study investigated the local prevalence of a cefazolin InE (CInE) and its association with staphylococcal blaZ gene types among MSSA isolates in the Chicago area. Four medical centers in Chicago, IL, contributed MSSA isolates. Cefazolin MICs (C-MIC) were determined at 24 h by the broth microdilution method using a standard inoculum (SI; 5 × 105 CFU/ml) and a high inoculum (HI; 5 × 107 CFU/ml). The CInE was defined as (i) a ≥4-fold increase in C-MIC between SI and HI and/or (ii) a pronounced CInE, i.e., a nonsusceptible C-MIC of ≥16 µg/ml at HI. PCR was used to amplify the blaZ gene, followed by agarose gel electrophoresis and sequencing to determine the gene type. Approximately 269 MSSA isolates were included. All but one isolate were susceptible to cefazolin at SI, and 97% remained susceptible at HI. A total of 196 isolates (73%) were blaZ positive, with the blaZ types led by gene type C (40%). CInE was seen in 45 blaZ-positive isolates (23%), with 44 (22%) presenting a ≥4-fold increase in C-MIC (SI to HI) and 5 (3%) a pronounced CInE. Four of the five met both definitions of CInE, two of which expressed the type A gene. The prevalence of a pronounced CInE associated with the type A blaZ gene from MSSA isolates in Chicago is low. Our predilection for cefazolin use, even early in the management of hospitalized MSSA infections, is tenable.

The Mark Coventry, MD, Award: Oral Antibiotics Reduce Reinfection After Two-Stage Exchange: A Multicenter, Randomized Controlled Trial.

BACKGROUND: Many patients develop recurrent periprosthetic joint infection after two-stage exchange arthroplasty of the hip or knee. One potential but insufficiently tested strategy to decrease the risk of persistent or recurrent infection is to administer additional antibiotics after the second-stage reimplantation. QUESTIONS/PURPOSES: (1) Does a 3-month course of oral antibiotics decrease the risk of failure secondary to infection after a two-stage exchange? (2) Are there any complications related to the administration of oral antibiotics after a two-stage exchange? (3) In those patients who develop a reinfection, is the infecting organism different from the initial infection? METHODS: Patients at seven centers randomized to receive 3 months of oral antibiotics or no further antibiotic treatment after operative cultures after the second-stage reimplantation were negative. Adult patients undergoing two-stage hip or knee revision arthroplasty for a periprosthetic infection who met Musculoskeletal Infection Society (MSIS) criteria for infection at the first stage were included. Oral antibiotic therapy was tailored to the original infecting organism(s) in consultation with an infectious disease specialist. MSIS criteria as used by the treating surgeon defined failure. Surveillance of patients for complications, including reinfection, occurred at 3 weeks, 6 weeks, 3 months, 12 months, and 24 months. If an organism demonstrated the same antibiotic sensitivities as the original organism, it was considered the same organism; no DNA subtyping was performed. Analysis was performed as intent to treat with all randomized patients included in the groups to which they were randomized. A log-rank survival curve was used to analyze the primary outcome of reinfection. At planned interim analysis (enrollment is ongoing), 59 patients were successfully randomized to the antibiotic group and 48 patients to the control group. Fifty-seven patients had an infection after TKA and 50 after a THA. There was no minimum followup for inclusion in this analysis. The mean followup was 14 months in the antibiotic group and 10 months in the control group. RESULTS: Patients treated with oral antibiotics failed secondary to infection less frequently than those not treated with antibiotics (5% [three of 59] versus 19% [nine of 48]; hazard ratio, 4.37; 95% confidence interval, 1.297-19.748; p = 0.016). Three patients had an adverse reaction to the oral antibiotics severe enough to cause them to stop taking the antibiotics early, and four patients who were randomized to that group did not take the antibiotics as directed. With the numbers available, there were no differences between the study groups in terms of the likelihood that an infection after treatment would be with a new organism (eight of nine in the control group versus one of three in the treatment group, p = 0.087). CONCLUSIONS: This multicenter randomized trial suggests that at short-term followup, the addition of 3 months of oral antibiotics appeared to improve infection-free survival. As a planned interim analysis, however, these results may change as the study reaches closure and the safety profile may yet prove risky. Further followup of this cohort of patients will be necessary to determine whether these preliminary results are durable over time. LEVEL OF EVIDENCE: Level I, therapeutic study.

Empirical therapy in Methicillin-resistant Staphylococcus Aureus infections: An Up-To-Date approach.

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be an important pathogen worldwide, with high prevalence of infection in both community and hospital settings. Timely and appropriate choice of empirical therapy in the setting of MRSA infection is imperative due to the high rate of associated morbidity and mortality with MRSA infections. Initial choices should be made based on the site and severity of the infection, most notably moderate skin and soft tissue infections which may be treated with oral antibiotics (trimethoprim-sulfamethoxazole, clindamycin, doxycycline/minocycline, linezolid) in the outpatient setting, versus choice of parenteral therapy in the inpatient setting of more invasive or severe disease. Though the current recommendations continue to strongly rely on vancomycin as a standard empiric choice in the setting of severe/invasive infections, alternative therapies exist with studies supporting their non-inferiority. This includes the use of linezolid in pneumonia and severe skin and skin structure infections (SSSI) and daptomycin for MRSA bacteremia, endocarditis, SSSIs and bone/joint infections. Additionally, concerns continue to arise in regards to vancomycin, such as increasing isolate MICs, and relatively high rates of clinical failures with vancomycin. Thus, the growing interest in vanomycin alternatives, such as ceftaroline, ceftobribole, dalbavancin, oritavancin, and tedizolid, and their potential role in treating MRSA infections.

Chicago Ebola Response Network (CERN): A Citywide Cross-hospital Collaborative for Infectious Disease Preparedness.

The 2014-2015 Ebola virus disease (EVD) epidemic and international public health emergency has been referred to as a "black swan" event, or an event that is unlikely, hard to predict, and highly impactful once it occurs. The Chicago Ebola Response Network (CERN) was formed in response to EVD and is capable of receiving and managing new cases of EVD, while also laying the foundation for a public health network that can anticipate, manage, and prevent the next black swan public health event. By sharing expertise, risk, and resources among 4 major academic centers, Chicago created a sustainable network to respond to the latest in a series of public health emergencies. In this respect, CERN is a roadmap for how a region can prepare to respond to public health emergencies, thereby preventing negative impacts through planning and implementation.

Treatment outcomes with cefazolin versus oxacillin for deep-seated methicillin-susceptible Staphylococcus aureus bloodstream infections.

Clinical preference for a semisynthetic penicillin (oxacillin or nafcillin) over cefazolin for deep-seated methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI) perseveres despite limited data to support this approach. A retrospective cohort study of patients treated for MSSA BSI with either oxacillin or cefazolin was performed across two medical centers in Chicago, IL. The outcome measures included documented in-hospital treatment failure, all-cause in-hospital mortality, duration of MSSA BSI, and incidence of documented adverse events. Of 161 patients with MSSA BSI, 103 (64%) received cefazolin, and 58 (36%) received oxacillin. The identified sources of BSI were central line (37.9%), osteoarticular (18%), and skin and soft tissue (17.4%). Patients with endocarditis (29/52 [44.2%]) and other deep-seated infections (23/52 [55.8%]) were classified under the subset of deep-seated infections (52/161 [32.3%]). Multivariate models found deep-seated infection (adjusted odds ratio [aOR], 4.52; 95% confidence interval [CI], 1.23 to 16.6; P = 0.023), metastatic disease (aOR, 4.21; 95% CI, 1.13 to 15.7; P = 0.033), and intensive care unit (ICU) onset of infection (aOR, 4.80; 95% CI, 1.26 to 18.4; P = 0.022) to be independent risk factors for in-hospital treatment failure. Treatment group was not an independent predictor of failure (aOR, 3.76; 95% CI, 0.98 to 14.4; P = 0.053). The rates of treatment failure were similar among cefazolin-treated (5/32 [15.6%]) and oxacillin-treated (4/20 [20.0%]) patients (P = 0.72) in the subset of deep-seated infections. Mortality was observed in 1 (1%) and 3 (5.2%) cases of cefazolin- and oxacillin-treated patients, respectively (P = 0.13). Cefazolin was not associated with higher rates of treatment failure and appears to be an effective alternative to oxacillin for treatment of deep-seated MSSA BSI.

Multicenter study of high-dose daptomycin for treatment of enterococcal infections.

Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggest that daptomycin at >6 mg/kg of body weight/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (>6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two hundred forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by Enterococcus faecalis in 49 (20%) and Enterococcus spp. in 21 (9%); overall, 204 (83%) isolates were VRE. Enterococcal infections included bacteremia (173, 71%) and intra-abdominal (35, 14%) and bone and joint (25, 10%) infections. The median dosage and duration of HD-daptomycin were 8.2 mg/kg/day (interquartile range [IQR], 7.7 to 9.7) and 10 days (IQR, 6 to 15), respectively. The overall clinical success rate was 89% (193/218), and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR, 2 to 5). The 30-day all-cause mortality rate was 27%, and 5 (2%) patients developed daptomycin-nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult-to-treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections.

A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis.

OBJECTIVES: Despite significant medical advances, infective endocarditis (IE) remains an infection associated with high morbidity and mortality. The objective was to assess the safety and efficacy of high-dose daptomycin, defined as ≥ 8 mg/kg/day, in patients with confirmed or suspected staphylococcal and/or enterococcal IE. METHODS: This was a multicentre, retrospective observational study (2005-11). Adult patients, not undergoing haemodialysis, with blood cultures positive for staphylococci or enterococci and a definitive or possible diagnosis of IE, who received daptomycin ≥ 8 mg/kg/day (based on total body weight) for ≥ 72 h were included. RESULTS: Seventy patients met the inclusion criteria and comprised 33 (47.1%) with right-sided IE (RIE), 35 (50%) with left-sided IE (LIE) and 2 with both RIE and LIE. Several patients had concomitant sites of infection, with bone/joint infection being most prevalent (12.9%). Sixty-five patients received daptomycin as salvage therapy. Pathogens were isolated from 64 patients, with methicillin-resistant Staphylococcus aureus as the most common organism (84.4%), followed by vancomycin-resistant Enterococcus faecium (7.8%). The median (IQR) daptomycin dose was 9.8 mg/kg/day (8.2-10.0 mg/kg/day), and was similar in RIE and LIE patients (9.8 and 9.3 mg/kg/day, respectively). A total of 24 (34.3%) received combination therapy. For those patients with pathogens isolated (n = 64), the organism was eradicated in 57 (89.1%) patients. Among 64 clinically evaluable patients, 55 (85.9%) achieved clinical success. No patients required discontinuation of high-dose daptomycin due to creatine phosphokinase elevations. CONCLUSIONS: Patients with both RIE and LIE had successful outcomes with high-dose daptomycin therapy. Additional clinical trials evaluating high daptomycin dosages in patients with IE are warranted.

Should draining wounds and sinuses associated with hip and knee arthroplasties be cultured?

We assessed the utility of culturing draining wounds or sinuses in evaluating periprosthetic joint infection (PJI). Fifty-five patients with a draining wound or sinus after total joint arthroplasty (28 knees, 27 hips) who had not received antibiotics for at least two weeks were prospectively studied. Superficial wound cultures were compared to intra-articular cultures to determine accuracy in isolating infecting organism(s). The superficial cultures were concordant with deep cultures in 26 of 55 cases (47.3%) and were more likely to generate polymicrobial results (27.3% vs. 10.9%; P=0.023). In 23 cases (41.8%), the superficial cultures would have led to a change in antibiotic regimen. Superficial cultures yielded bacterial growth in 8 of the 10 cases (80%) when deep cultures and further work-up suggested the absence of deep infection. Given the potential to misguide diagnosis and treatment, we recommend against obtainment of superficial cultures in patients with a draining wound or sinus following hip or knee arthroplasty.

Recurrent Failures After 2-Stage Exchanges are Secondary to New Organisms Not Previously Covered by Antibiotics.

Background: Prior studies have shown that the majority of re-infections following two-stage revisions are due to organisms different from the initial organisms identified. It remains unknown whether these new organisms were susceptible to the antibiotics given (indicating the patient likely developed another infection following successful treatment) or not susceptible (indicating these organisms may have been initially present, but were not identified, and thus, inadequately treated). The purpose of this study was to determine if bacteria identified at time of re-infection following two-stage revisions were susceptible to the antibiotics administered during treatment of the index infection, in order to understand if these are new infections or from organisms that were present but not initially identified. Methods: Thirty failures (19 knees and 11 hips) following two-stage revisions from four institutions were identified. Cultures and antibiotic sensitivities were used to determine whether the re-infectious organisms were new and if they were susceptible to the antibiotics initially given. Results: Twenty-five (83.3%) re-infections were due to new organisms. Of these re-infections from new organisms, 16 (64.0%) were susceptible to the antibiotics previously administered, suggesting they were new infections rather than persistent infections from organisms that were not detected during initial treatment. No statistically significant differences in demographics or time to revision were observed when comparing by organism type (new vs. repeat) or by antibiotic susceptibility. Conclusions: Failures following two-stage revisions are frequently due to organisms different than those identified prior to two-stage revision and are likely new infections rather than persistent infections from undetected organisms.

Diagnosis of periprosthetic joint infections of the hip and knee.

No preferred test for diagnosis of periprosthetic joint infection exists, and the algorithm for the workup of patients suspected of infection remains unclear. The work group evaluated the available literature to determine the role of each diagnostic modality and devise a practical algorithm that allows physicians to reach diagnosis of periprosthetic joint infection. Ten of the 15 recommendations have strong or moderate evidence in support. These include matters involving erythrocyte sedimentation rate and C-reactive protein level testing, knee and hip aspiration, and stopping the use of antibiotics prior to obtaining intra-articular cultures. The group recommends against the use of intraoperative Gram stain but does recommend the use of frozen sections of peri-implant tissues in reoperation patients in whom infection has not been established, as well as multiple cultures in reoperation patients being assessed for infection. The group recommends against initiating antibiotic treatment in patients with suspected infection until after joint cultures have been obtained, but recommends that prophylactic preoperative antibiotics not be withheld in patients at lower probability for infection.

2020 Mark Coventry Award: Microorganism-directed oral antibiotics reduce the rate of failure due to further infection after two-stage revision hip or knee arthroplasty for chronic infection: a multicentre randomized controlled trial at a minimum of two years.

AIMS: The aim of this study was to determine if a three-month course of microorganism-directed oral antibiotics reduces the rate of failure due to further infection following two-stage revision for chronic prosthetic joint infection (PJI) of the hip and knee. METHODS: A total of 185 patients undergoing a two-stage revision in seven different centres were prospectively enrolled. Of these patients, 93 were randomized to receive microorganism-directed oral antibiotics for three months following reimplantation; 88 were randomized to receive no antibiotics, and four were withdrawn before randomization. Of the 181 randomized patients, 28 were lost to follow-up, six died before two years follow-up, and five with culture negative infections were excluded. The remaining 142 patients were followed for a mean of 3.3 years (2.0 to 7.6) with failure due to a further infection as the primary endpoint. Patients who were treated with antibiotics were also assessed for their adherence to the medication regime and for side effects to antibiotics. RESULTS: Nine of 72 patients (12.5%) who received antibiotics failed due to further infection compared with 20 of 70 patients (28.6%) who did not receive antibiotics (p = 0.012). Five patients (6.9%) in the treatment group experienced adverse effects related to the administered antibiotics severe enough to warrant discontinuation. CONCLUSION: This multicentre randomized controlled trial showed that a three-month course of microorganism-directed, oral antibiotics significantly reduced the rate of failure due to further infection following a two-stage revision of total hip or knee arthroplasty for chronic PJI. Cite this article: Bone Joint J 2020;102-B(6 Supple A):3-9.

Health care-associated pneumonia (HCAP): a critical appraisal to improve identification, management, and outcomes--proceedings of the HCAP Summit.

Increasingly, patients are receiving treatment at facilities other than hospitals, including long-term-health care facilities, assisted-living environments, rehabilitation facilities, and dialysis centers. As with hospital environments, nonhospital settings present their own unique risks of pneumonia. Traditionally, pneumonia in these facilities has been categorized as community-acquired pneumonia (CAP). However, the new designation for pneumonias acquired in these settings is health care-associated pneumonia (HCAP), which covers pneumonias acquired in health care environments outside of the traditional hospital setting and excludes hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and CAP. Although HCAP is currently treated with the same protocols as CAP, recent evidence indicates that HCAP differs from CAP with respect to pathogens and prognosis and, in fact, more closely resembles HAP and VAP. The HCAP Summit convened national infectious disease opinion leaders for the purpose of analyzing current literature, clinical trial data, diagnostic considerations, therapeutic options, and treatment guidelines related to HCAP. After an in-depth analysis of these areas, the infectious disease investigators participating in the summit were surveyed with regard to 10 clinical practice statements. The results were then compared with results of the same survey as completed by 744 Infectious Diseases Society of America members. The similarities and differences between those survey results are the basis of this publication.

University HealthSystem Consortium quality performance benchmarking study of the insertion and care of central venous catheters.

We report data from an observational benchmarking study of adherence to recommended practices for insertion and maintenance of central venous catheters at a heterogeneous group of academic medical centers. These centers demonstrated a need for significant improvement in implementation and documentation of quality performance measures for the prevention of catheter-related bloodstream infections.