Central line-associated Rhizobium radiobacter bloodstream infection in two allogeneic hematopoietic cell transplant recipients.

INTRODUCTION: Rhizobium radiobacter is a gram-negative, opportunistic phytopathogen that rarely causes human infections. We report two cases of Rhizobium radiobacter central line-associated bloodstream infection (CLABSI) in allogeneic hematopoietic cell transplantation (alloHCT) recipients. We review previous reports and common microbiological characteristics associated with this organism. CASE REPORTS: Two adult males developed R. radiobacter CLABSIs at day +81 and day +77 post-alloHCT. Patient one was asymptomatic on presentation while patient two was febrile. One patient had a polymicrobial infection, which has not been previously described. The presence of high-level ceftazidime resistance in both patients suggests third-generation cephalosporin resistance may be more common than previously recognized. MANAGEMENT AND OUTCOME: For both patients, microbiologic clearance was achieved through peripherally inserted central catheter removal and initiation of intravenous cefepime. Antibiotic therapy was narrowed to oral levofloxacin for a total 14-day course from the time of first negative blood culture. There has been no subsequent recurrence of R. radiobacter infection at 12 and 5 months of follow-up for patients one and two, respectively. DISCUSSION: These two cases add to the scant literature characterizing R. radiobacter infection following alloHCT. Immunosuppressive agents for graft-versus-host disease prophylaxis may have predisposed these patients to R. radiobacter infection. Our reports, and previously reported cases, suggest R. radiobacter exhibits low virulence, mild symptom burden, and does not confer a high mortality risk. In the alloHCT setting, further accumulation of cases is needed to aid in understanding clinical features and characteristics of R. radiobacter infection.

Alternative pneumocystis prophylaxis in solid organ transplant recipients at two large transplant centers.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice for Pneumocystis jirovecii pneumonia (PJP) prophylaxis and has activity against other opportunistic infections (OIs) after solid organ transplant (SOT). We aimed to describe the incidence, reasons for and outcomes of use of alternative prophylactic agents (APAs) across SOT programs in our high volume centers. METHODS: Solid organ transplant recipients (SOTRs) at our centers from 1/2015-12/2016 were identified. Pharmacy records identified APA (pentamidine, atovaquone, or dapsone) use within 1 year. Records were reviewed for allergies, laboratory values at APA initiation, diagnostic tests for TMP-SMX-preventable OIs, and APA side effects. RESULTS: An APA was initiated in 105/1173 (8.9%) SOTRs. Of these, 51 (48.6%) were because of sulfonamide allergy recorded pre-SOT, mostly rash/hives (58.8%). The remaining 54 (51.4%) had TMP-SMX discontinued post-SOT, mostly for neutropenia (48%) and renal effects (34%). Differences occurred across programs, with kidney transplant never stopping TMP-SMX for renal issues. Of those changed to APAs post-transplant, 19 (35%) were later successfully re-challenged with TMP-SMX. With thresholds in mind, 67 (64%) received an APA unnecessarily, accounting for up to $100 000/y excess cost. Potential TMP-SMX-preventable OIs occurred in 7 (5 Nocardia; 2 PJP). APA side effects occurred in 14/105 (13.3%). CONCLUSIONS: Use of APAs for PJP prophylaxis after SOT is less than previously reported but often unwarranted. Such decisions require scrutiny to avoid TMP-SMX-preventable OIs, cost and important APA side effects. Use of reasonable thresholds for cessation of TMP-SMX and data-driven approaches to re-challenge would substantially reduce APA use.

Clinical and Microbiological Outcomes in Obese Patients Receiving Colistin for Carbapenem-Resistant Gram-Negative Bloodstream Infection.

Carbapenem-resistant infections are associated with poor outcomes, and treatment options are limited. Colistin is one of few antibiotics which retain in vitro activity against carbapenem-resistant pathogens. However, despite the availability of international consensus guidelines for the dosing of polymyxins, there are limited data on the effects of dosing on clinical outcomes among obese patients with carbapenem-resistant Gram-negative bacteremia. This retrospective study evaluated whether obesity was associated with day 7 global cure rates among patients with carbapenem-resistant Gram-negative bacteremia who were treated with an ideal body weight (IBW)-based colistin dosing regimen. Secondary outcomes included microbiological cure, clinical cure, length of hospital stay, in-hospital mortality, and day 7 acute kidney injury. After screening to identify 167 patients, 77 (46.1%) and 90 (53.9%) were classified as obese and nonobese, respectively. Patient characteristics were well balanced at baseline, except that obese patients were more often female and received a higher daily dose per IBW (3.7 versus 2.9 mg/kg/day, P = 0.03). Global cure rates were similar between groups (44.2% for obese versus 55.6% for nonobese, P = 0.14). After adjusting for baseline differences, obesity was not a significant predictor of global cure (adjusted odds ratio [AOR], 0.59; 95% confidence interval [CI], 0.31 to 1.11; P = 0.10). Obesity was associated with a lower likelihood of microbiological clearance (72.7% versus 91.1%, P = 0.02). No other secondary outcome differences were observed, though each outcome was numerically worse among obese patients. Obesity was not associated with differences in global cure rates. However, the difference in microbiological clearance warrants further investigation.

Meropenem-Vaborbactam as Salvage Therapy for Ceftazidime-Avibactam-Resistant Klebsiella pneumoniae Bacteremia and Abscess in a Liver Transplant Recipient.

We report a case of a 24-year-old liver transplant recipient who developed hepatic artery thrombosis and graft failure, which was complicated by subphrenic abscess and persistent Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bacteremia. Ceftazidime-avibactam treatment led to emergence of resistance, and alternative combination therapy failed due to persistent infection and toxicity. The infection resolved after initiation of meropenem-vaborbactam, which created a bridge to retransplantation. Treatment-emergent ceftazidime-avibactam resistance is increasingly recognized, suggesting a role for meropenem-vaborbactam.

Impact of asymptomatic bacteriuria incidence and management post-kidney transplantation.

OBJECTIVE: Urinary tract infections (UTIs) are the most commonly occurring infectious complication following kidney transplantation. Questions remain regarding whether asymptomatic bacteriuria (ASB) should be treated. The aim was to evaluate the incidence and management of ASB in kidney transplant recipients at a large academic medical center. METHODS: All subjects receiving an isolated kidney transplant between September 2012 and October 2016, and with at least one ASB episode were included. Demographics, symptomatology, and urine culture data were collected on subjects with bacteriuria in the first year post-transplant. Cultures were classified by symptoms, ASB treatment trends were analyzed, and ASB-to-UTI progression was compared between ASB treatment and non-treatment. RESULTS: A total of 527 subjects were transplanted with 64 developing at least one ASB episode. The incidence of ASB was 12.1% and treated 74.6% of the time. Neither lack of ASB treatment (P = 0.463) nor ASB within the first month post-transplant (P = 0.303) were associated with ASB-to-UTI progression. CONCLUSION: Despite high ASB treatment rate, this was not found to be protective against ASB-to-UTI progression. ASB within the first month post-transplant also did not correlate with increased progression risk. These results suggest minimization of ASB treatment in kidney transplant recipients remains an important antimicrobial stewardship target.

Penicillin allergy skin testing as an antibiotic stewardship intervention reduces alternative antibiotic exposures in hematopoietic stem cell transplant recipients.

BACKGROUND: Antibiotic allergy de-labeling using penicillin allergy skin testing (PAST) can reduce the use and cost of alternative, non-ß-lactam antibiotics in general inpatient populations. This strategy's role in hematopoietic stem cell transplant (HSCT) recipients is unclear. METHODS: This study aimed to determine the effect of a pre-transplant PAST protocol on antibiotic use, days of therapy (DOT), and cost in an immunocompromised population at a single center from 7/1/2010-2/1/2019. Patients who received chimeric antigen receptor (CAR) T-cell therapy and those who underwent transplantation in the outpatient setting were excluded. RESULTS: Of 1560 patients who underwent inpatient HSCT during the study period, 208 reported ß-lactam allergy (136/844 [16%] pre- and 72/716 [10%] post-implementation; P < .001). PAST was performed on 7% and 54% of HSCT recipients pre- and post-implementation, respectively. Only two positive PAST were noted. There were no adverse reactions to PAST. There were no significant differences in the disease and transplant characteristics between the two groups. Days of therapy and cost of alternative antibiotics significantly decreased post-implementation (mean 788 vs 627 days, P = .01; mean $24 425 vs $17 518, P = .009). CONCLUSION: Penicillin allergy skin testing adjudicates reported ß-lactam allergy in HSCT recipients, lowering use, DOT, and cost of alternative antibiotics and promoting effective formulary agents to treat immunocompromised HSCT recipients.

Real-world use-Isavuconazole at a large academic medical center.

BACKGROUND: Isavuconazole use in the real-world setting has not been extensively described. Subgroups of patients with particular prognostic significance, such as previous triazole prophylaxis or treatment and the important subgroup treated empirically for invasive fungal infection, have beforehand been excluded from trials. OBJECTIVES: We aimed to determine treatment response and safety in these patients at a large US transplant and cancer centre. PATIENTS/METHODS: We conducted a retrospective cohort study of all adult inpatients administered ≥3 doses of isavuconazole between June 2015 and October 2017. RESULTS: Ninety-one adults were identified. Six (7%) received primary prophylaxis, 10 (11%) treatment then secondary prophylaxis and 75 (82%) treatment only. Overall treatment response was 62%. Six-week mortality was 24%. Sixty-three per cent of 32 patients treated with isavuconaozle following prophylaxis with another antifungal agent exhibited a treatment response. Among 49 patients switched from treatment with another agent, 53% had a treatment response. Thirty-four patients received isavuconazole empirically, and 65% demonstrated a treatment response. Individuals given isavuconazole prophylaxis developed no breakthrough invasive fungal infections. One patient discontinued isavuconazole due to hepatotoxicity. CONCLUSIONS: Real-world isavuconazole use appears safe and is associated with treatment responses in varied patients including critically important subgroups previously unreported.

A pharmacist-driven antimicrobial stewardship intervention targeting cytomegalovirus viremia in ambulatory solid organ transplant recipients.

BACKGROUND: There is a growing need for robust antimicrobial stewardship interventions in both ambulatory and solid organ transplant (SOT) populations. METHODS: A retrospective quasi-experiment was conducted to evaluate the impact of a pharmacist-driven antimicrobial stewardship intervention targeting cytomegalovirus (CMV) viremia in ambulatory SOT recipients. The intervention consisted of (a) real-time CMV DNA surveillance and result notification conducted by the pharmacist and (b) recommendations for the optimization of drug therapy provided at the time of result notification. The intervention period was compared to a pre-intervention period of usual care. Of 431 adult SOT recipients who had an initial quantifiable CMV viral load in the ambulatory setting, 185 received antiviral induction therapy and were included for analysis. RESULTS: Significantly fewer patients in the intervention period reached a CMV viral load >10 000 IU/mL immediately prior to treatment (10.6% vs 27.3%; P = 0.004), and a significantly greater proportion of patients in the intervention period achieved CMV eradication at 21 days (84.5% vs 71.7%; P = 0.038). Additional differences favoring the intervention period were antiviral initiation within 5 days of the first quantifiable CMV DNA (62.4% vs 55.0%; P = 0.02) and time-to-CMV eradication (25.5 vs 28.9 days; P = 0.003). Although not significant, there were also numerical reductions in CMV-related hospital admissions (11.9% vs 19.0%; P = 0.188) and CMV disease (5.9% vs 12.0%; P = 0.151) during the intervention period, as well as fewer episodes of CMV resistance at 1-year (2.3% vs 4.0%; P = 0.689). CONCLUSION: Together, these findings suggest a potential role for pharmacist involvement in CMV surveillance and treatment optimization in ambulatory SOT recipients.

Outpatient use of ceftaroline fosamil versus vancomycin for osteoarticular infection: a matched cohort study.

OBJECTIVES: There are few convenient intravenous options for long-term outpatient treatment of osteoarticular infection (OAI) and limited effectiveness and safety data exist for this off-label use of ceftaroline. The objective of this study was to describe the long-term effectiveness and safety of ceftaroline for the treatment of OAI. METHODS: This was a matched retrospective cohort study of patients receiving ceftaroline- or vancomycin-based therapy for OAI in the outpatient setting. Patients were matched according to infection subtype, anatomical site and microbiology. The primary endpoint was 180 day infection-related readmission (IRR). Secondary endpoints included all-cause readmission, time-to-IRR and adverse event incidence. RESULTS: The final matched cohort consisted of 50 ceftaroline-treated patients and 50 vancomycin-treated patients. The IRR incidence was 22% for ceftaroline patients and 30% for vancomycin patients; OR = 0.66 (95% CI = 0.27-1.62; P = 0.362). There was no significant difference between groups in all-cause readmission or time-to-IRR. Attributable adverse event incidences were 24% and 18% for ceftaroline and vancomycin, respectively. Rash (10%) and nausea (6%) were the most common ceftaroline adverse events, while acute kidney injury (6%) and rash (4%) were the most common vancomycin adverse events. CONCLUSIONS: Attributable readmission and adverse events were common among patients treated with outpatient intravenous antimicrobials for OAI. This study found no appreciable difference in effectiveness or tolerability between ceftaroline- or vancomycin-treated patients. Although further research will be important to delineate the role of ceftaroline in the management of OAI, data derived from this study may aid clinicians in determining therapy when limited options exist.

The Penn Medicine COVID-19 Therapeutics Committee-Reflections on a Model for Rapid Evidence Review and Dynamic Practice Recommendations During a Public Health Emergency.

The Penn Medicine COVID-19 Therapeutics Committee-an interspecialty, clinician-pharmacist, and specialist-front line primary care collaboration-has served as a forum for rapid evidence review and the production of dynamic practice recommendations during the 3-year coronavirus disease 2019 public health emergency. We describe the process by which the committee went about its work and how it navigated specific challenging scenarios. Our target audiences are clinicians, hospital leaders, public health officials, and researchers invested in preparedness for inevitable future threats. Our objectives are to discuss the logistics and challenges of forming an effective committee, undertaking a rapid evidence review process, aligning evidence-based guidelines with operational realities, and iteratively revising recommendations in response to changing pandemic data. We specifically discuss the arc of evidence for corticosteroids; the noble beginnings and dangerous misinformation end of hydroxychloroquine and ivermectin; monoclonal antibodies and emerging viral variants; and patient screening and safety processes for tocilizumab, baricitinib, and nirmatrelvir-ritonavir.

The Implementation and Effect of Weekend Pharmacy-Driven Antimicrobial Stewardship Services at a Large Academic Medical Center.

BACKGROUND: In September 2018, pharmacy antimicrobial stewardship (AMS) services were expanded to include weekends at this academic medical center. Activities performed by AMS pharmacists on the weekends include blood culture rapid diagnostic (RDT) review, antiretroviral therapy (ART) review, prospective audit and feedback (PAF) utilizing clinical decision support, vancomycin dosing, and operational support. The purpose of this study was to assess the operational and clinical impact of these expanded AMS services. METHODS: This single-center, quasi-experimental study included data from weekends before (9/2017-11/2017) and after (9/2018-11/2018) implementation. The descriptive primary outcome was the number of activities completed for each AMS activity type in the post-implementation group only. Secondary outcomes were time to AMS opportunity resolution, time to escalation or de-escalation following PAF or RDT alert, time to resolution of miscellaneous AMS related opportunities, length of stay (LOS), and antimicrobial use outcomes. RESULTS: During the post-implementation period 1258 activities were completed, averaging 97/weekend. Inclusion criteria for time to resolution outcomes were met by 72 patients pre-implementation and 59 patients post. The median (IQR) time to AMS opportunity resolution decreased from 18.5 hours pre-intervention (7.7-35.7) to 8.5 hours post-intervention (IQR 1.8-14.0), p < 0.01. Time to escalation was 11.6 hours compared to 1.7 hours (p = 0.1), de-escalation 16.7 hours compared to 10.8 hours (p = 0.03), and miscellaneous opportunity 40.8 hours compared to 13.2 hours (p = 0.01). No differences were observed in LOS or antimicrobial use outcomes. CONCLUSION: Presence of pharmacist-driven weekend AMS services significantly reduced time to resolution of AMS opportunities. These data support the value of weekend AMS services.

Evaluation of a hospital-wide vancomycin-dosing nomogram in patients with continuous-flow left ventricular assist devices.

INTRODUCTION: Hemodynamic derangements due to heart failure are associated with alterations in pharmacokinetics. Although use of mechanical circulatory support mitigates such derangements, little evidence is available regarding pharmacokinetics in patients with LVADs. A previous pharmacokinetic analysis of vancomycin among patients with LVADs observed a reduced volume of distribution and clearance compared with estimates based on population kinetics. METHODS: A total of 28 adult patients with LVADs hospitalized between January 2014 and May 2018 who received vancomycin through a pharmacist dosing consult were included. Internal medicine patients without heart failure receiving vancomycin were enrolled in a 2:1 fashion to make a control group. Exclusion criteria were unstable renal function, ESRD, acute decompensation, cardiac surgery within the preceding 5 days, or weight >110 kg. RESULTS: No difference was observed in the proportion achieving goal trough (64% of LVAD patients vs 71% control patients, p = 0.50). However, mean trough was significantly higher among LVAD patients (23.4 mg/L vs 17.7 mg/L, p = 0.017). Furthermore, there was a significant difference in the distribution of trough levels (p = 0.025) with LVAD patients being more likely to attain levels >25 mg/L (32% vs 14%) and less likely to have troughs <10 mg/L (4% vs 14%). A numerically greater number of LVAD patients experienced nephrotoxicity but this did not reach statistical significance (32% vs 18%, p = 0.14). CONCLUSION: The use of vancomycin in LVAD patients may result in higher trough levels when compared to internal medicine patients. Increased monitoring or conservative dosing may be warranted to improve safety and efficacy.

Real-world, Multicenter Experience With Meropenem-Vaborbactam for Gram-Negative Bacterial Infections Including Carbapenem-Resistant Enterobacterales and Pseudomonas aeruginosa.

BACKGROUND: We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of gram-negative infections (GNIs), primarily including carbapenem-resistant Enterobacterales (CRE). METHODS: This is a real-world, multicenter, retrospective cohort within the United States between 2017 and 2020. Adult patients who received MEV for ≥72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCOs) and was examined by multivariable logistic regression analysis (MLR). RESULTS: Overall, 126 patients were evaluated from 13 medical centers in 10 states. The most common infection sources were respiratory tract (38.1%) and intra-abdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in 4 patients: nephrotoxicity (n = 2), hepatoxicity (n = 1), and rash (n = 1). CART-BP between early and delayed treatment was 48 hours (P = .04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (adusted odds ratio, 0.277; 95% CI, 0.081-0.941). CONCLUSIONS: Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNIs, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCOs.

Itraconazole vs. posaconazole for antifungal prophylaxis in patients with acute myeloid leukemia undergoing intensive chemotherapy: A retrospective study.

OBJECTIVE: The objective of this study was to compare itraconazole with posaconazole for antifungal prophylaxis in acute myeloid leukemia (AML) patients undergoing intensive chemotherapy. METHODS: Adult patients with AML received either itraconazole or posaconazole for antifungal prophylaxis while undergoing intensive chemotherapy. The primary endpoint was incidence of prophylaxis failure (change in antifungal agent due to suspected invasive fungal infection [IFI], drug intolerance, drug interaction, or adverse event). RESULTS: From February 2016 to January 2018, 90 patients were included in the itraconazole group and 45 patients in the posaconazole group. Prophylaxis failure occurred in 88% of itraconazole recipients compared with 33% of posaconazole recipients (P<0.001). The primary reason for prophylaxis failure with itraconazole was suspected IFI (58%) whereas for posaconazole, failure predominantly related to drug interaction (60%). An antifungal regimen was continued upon discharge in 47% of itraconazole recipients compared with 9% of posaconazole recipients (P<0.001). The use of breakthrough IFI diagnostic tests was not significantly different in the two groups. A larger proportion of drug concentrations were collected in the posaconazole group. CONCLUSIONS: In AML patients undergoing intensive chemotherapy, posaconazole was associated with significantly lower rates of prophylaxis failure and less need for continued antifungal therapy on discharge compared with itraconazole.

Real-world Multicenter Analysis of Clinical Outcomes and Safety of Meropenem-Vaborbactam in Patients Treated for Serious Gram-Negative Bacterial Infections.

Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV.

Recommended foscarnet dose is not associated with improved outcomes in cytomegalovirus salvage therapy.

BACKGROUND: Cytomegalovirus (CMV) infection causes significant morbidity and mortality in transplant recipients. Ganciclovir and valganciclovir have proven efficacy but are limited by resistance and toxicity, whereas foscarnet typically retains activity when CMV has become resistant to other antivirals. Foscarnet dosing used in practice may be discordant with what is recommended in product labeling, as the result of an unconventional dosing nomogram or prescriber preference; however, it is unknown how discordant foscarnet dosing affects outcomes. OBJECTIVE: Our purpose was to characterize the relationship between initial foscarnet dosing intensity (relative to product labeling) and key effectiveness and safety endpoints. STUDY DESIGN: This single-center, retrospective study included immunosuppressed adults with CMV viremia who received foscarnet between January 2012-July 2017. Subjects were divided into low dose (LD) and non-low dose (NLD) groups, according to foscarnet dose intensity. The primary endpoint was time-to-CMV eradication. Secondary endpoints included time-to-CMV clearance, acute kidney injury, hematologic toxicity, and mortality. RESULTS: Of 87 subjects, 38 met inclusion. Primary immunosuppression reasons were solid organ (63%) or hematopoietic cell transplant (29%). Seventeen and 21 subjects were in the LD and NLD groups, respectively. Median time-to-CMV eradication was 17 days (LD group) versus 13 days (NLD group), p = 0.823. Median time-to-CMV clearance was also non-significant (p = 0.505). There was no association between initial foscarnet dosing intensity and acute kidney injury, hematologic toxicity, or mortality (24% in both groups). CONCLUSIONS: These findings suggest outcomes may be sensitive to other factors and underscore the need for further studies to improve understanding of foscarnet dosing in immunosuppressed patients.

Evaluation of an electronic antimicrobial time-out on antimicrobial utilization at a large health system.

We evaluated the impact of an electronic health record based 72-hour antimicrobial time-out (ATO) on antimicrobial utilization. We observed that 6 hours after the ATO, 21% of empiric antimicrobials were discontinued or de-escalated. There was a significant reduction in the duration of antimicrobial therapy but no impact on overall antimicrobial usage metrics.

Implementation of a Stewardship Initiative on Respiratory Viral PCR-based Antibiotic Deescalation.

OBJECTIVE: Respiratory viral polymerase chain reaction (RV PCR) tests assist in rapidly identifying viral pathogens and differentiating viral versus bacterial causes of pneumonia. Studies evaluating the use of RV PCR tests on antibiotic use in adults have demonstrated mixed results. We implemented an antimicrobial stewardship (ASP) intervention for patients with a positive RV PCR test result who were receiving broad-spectrum antibiotics and aimed to assess the impact on antibiotic usage. METHODS: Retrospective quasi-experimental study of adult hospitalized patients comparing time to antibiotic deescalation, duration of antibiotic therapy, and antiviral use preintervention (January-March 2016) and postintervention (January-March 2017). RESULTS: Of 172 ASP alerts reviewed, 55 (32%) were considered actionable. Of these, 47% of interventions were accepted. No significant difference was observed in median time to antibiotic deescalation (pre: 2.7 days vs post: 2.3 days, p=0.88). Time to discontinuation of antimicrobial therapy pre- and postintervention was reduced from 4 to 1.9 days (p=0.057) for piperacillin-tazobactam, from 2.7 to 1.8 days (p=0.75) for ceftriaxone, and from 3.6 to 2 days (p=0.4) for levofloxacin, respectively. Time to initiation of oseltamivir for influenza was significantly shorter in the postintervention group (pre: 11.3 hrs vs post: 3.6 hrs, p=0.02). CONCLUSION: A third of patients receiving broad-spectrum antibiotics with a positive RV PCR had an opportunity for antimicrobial optimization, although this did not translate into a significant impact on the time to antibiotic deescalation or overall antibiotic use. Combination of RV PCR results with biomarkers to rule out bacterial coinfections and chest radiographic findings may help enhance the likelihood of accepted antibiotic deescalation recommendations and represents an area of future research.

Trowels and Tribulations: Review of Antimicrobial-Impregnated Bone Cements in Prosthetic Joint Surgery.

Antimicrobial-impregnated bone cement (AIBC) is a staple of contemporary orthopedic surgery and has been used to either treat or prevent prosthetic joint infection. Applied intraoperatively during primary arthroplasty or prosthetic joint exchange, this drug-delivery vehicle has become a popular means of maximizing drug concentrations within a joint space while minimizing systemic exposure. Antimicrobial characteristics conducive to cement loading include availability of a crystalline powder formulation, molecular characteristics, minimal impact on cement integrity, and other variables promoting drug elution. Antimicrobials most commonly incorporated into cements are vancomycin and aminoglycosides, usually in combination due to synergistic antibacterial activity and enhanced cement elution. Other classes include the ß-lactams, lipopeptides, oxazolidinones, and antifungals. With the exception of several commercially available AIBCs, most products are compounded extemporaneously without a formal safety or efficacy assessment. Few randomized controlled trials have been conducted to assess the benefit or optimal use of these cement preparations, and variable methodology renders cross-study comparison challenging. Given the lack of standardization and multidisciplinary oversight often seen with practical AIBC use, additional data are needed. This review presents information intended to guide AIBC preparation, selection, dosing, and safe use. In addition, opportunities for best practice development, antimicrobial stewardship, and future research are discussed.