Use of single agent Cefotetan for Gustilo-Anderson type III open fracture prophylaxis.

INTRODUCTION: The prophylactic intravenous antibiotic regimen for Gustilo-Anderson Type III open fractures traditionally consists of cefazolin with an aminoglycoside plus penicillin for gross contamination. Cefotetan, a second-generation cephalosporin, offers a wide spectrum of activity against both aerobes and anaerobes as well as against Gram-positive and Gram-negative bacteria. Cefotetan has not been previously established within orthopedic surgery as a prophylactic intravenous agent. PATIENTS AND METHODS: Cefotetan monotherapeutic prophylaxis versus any other antibiotic regimen (standard/literature-supported and otherwise) was studied for patient encounters between September 2010 and December 2019 within a single Level 1 regional trauma center. Patient comorbidities, preoperative fracture characteristics, and in-hospital/operative metrics (including length of stay [LOS], number of antibiotic doses, and antibiotic costs [US$]) were included for analysis. Postoperative outcomes up to 1 year included rates of surgical site infection (SSI), deep infection necessitating return to the operating room (OR), non-union, prescribed outpatient antibiotics, hospital readmissions, and related returns to the emergency department (ED). Sensitivity analyses were also conducted to include standard/literature-supported antibiotic regimens as a nested random factor within the non-cefotetan cohort. RESULTS: The nested variable accounting for standard/literature-supported antibiotic regimens had no significant effect in any model for any outcome (for each, P ≥ 0.302). Thus, 1-year data for 138 Type III open fractures were included, accounting for only the binary effect of cefotetan (n = 42) versus non-cefotetan cohorts. The cohorts did not differ significantly at baseline. The cefotetan cohort received fewer in-house dose/day antibiotics (P < 0.001), was less likely to receive outpatient antibiotics in the following year (P = 0.023), had decreased return to the OR (35.7% versus 54.2%, P = 0.045), and demonstrated non-union rates of 16.7% versus 28.1% (P = 0.151). When adjusted for length of stay (LOS), the dose/day total costs for antibiotics were $8.71/day more expensive for the cefotetan cohort (P = 0.002). Type III open fractures incurred overall rates of SSI reaching 16.7% in the cefotetan cohort and 14.7% for non-cefotetan (P = 0.773). Deep infections necessitating return to the OR were 9.5% and 11.6%, respectively (P = 0.719). CONCLUSION: Cefotetan alone may provide superior antibiotic stewardship with similar infectious sequalae compared to more traditional antibiotic prophylaxis regimens for Gustilo-Anderson Type III open long bone fractures. LEVEL OF EVIDENCE: Level III Retrospective Cohort Study.

A retrospective cohort study assessing acute kidney injury and renal recovery among septic patients empirically treated with vancomycin piperacillin-tazobactam versus vancomycin cefepime.

Vancomycin plus piperacillin-tazobactam (VPT) is a commonly used antimicrobial regimen for septic patients. VPT is more nephrotoxic than other regimens such as vancomycin plus cefepime (VC) when given over several days. This risk of nephrotoxicity is less clear when VPT is given for initial empiric therapy in sepsis and de-escalated quickly based on evolving clinical information. The objective of this study was to assess nephrotoxicity among septic patients empirically treated with either VPT or VC at initial clinical presentation. We conducted a retrospective study of septic patients who received VPT or VC within 12 h of presentation to the emergency department. The primary outcomes were acute kidney injury (AKI) and renal recovery 72 h after presentation. For the total of 418 patients, 306 received VPT and 112 received VC. Rates of AKI at 72 h were 15.2% for VPT patients and 11.0% for VC patients [p = 0.44]. Among patients with AKI at presentation, 16.3% of VPT patients had AKI at 72 h compared to 8.9% of VC patients [p = 0.19]. Among those without AKI at presentation, 14.2% VPT patients and 16.7% VC patients had AKI at 72 h [p = 0.71]. Renal recovery rates for patients with AKI at presentation were 42.3% for VPT patients versus 40.3% for VC patients [p = 0.78]. In-hospital renal replacement therapy occurred in 6.2% VPT patients and 0.9% VC patients [p = 0.024]. Therefore, initial empiric therapy with VPT in sepsis may not confer increased risk of AKI when de-escalated appropriately.

Treatment of Community-Acquired Pneumonia in Immunocompromised Adults: A Consensus Statement Regarding Initial Strategies.

BACKGROUND: Community-acquired pneumonia (CAP) guidelines have improved the treatment and outcomes of patients with CAP, primarily by standardization of initial empirical therapy. But current society-published guidelines exclude immunocompromised patients. RESEARCH QUESTION: There is no consensus regarding the initial treatment of immunocompromised patients with suspected CAP. STUDY DESIGN AND METHODS: This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the treatment of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus. RESULTS: The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiologic workup, general principles of empirical therapy, and empirical therapy for specific pathogens. INTERPRETATION: This document offers general suggestions for the initial treatment of the immunocompromised patient who arrives at the hospital with pneumonia.

Early Infectious Diseases Specialty Intervention Is Associated With Shorter Hospital Stays and Lower Readmission Rates: A Retrospective Cohort Study.

Background: Intervention by infectious diseases (ID) physicians improves outcomes for inpatients in Medicare, but patients with other insurance types could fare differently. We assessed whether ID involvement leads to better outcomes among privately insured patients under age 65 years hospitalized with common infections. Methods: We performed a retrospective analysis of administrative claims data from community hospital and postdischarge ambulatory care. Patients were privately insured individuals less than 65 years old with an acute-care stay in 2014 for selected infections, classed as having early (by day 3) or late (after day 3) ID intervention, or none. Key outcomes were mortality, cost, length of the index stay, readmission rate, mortality, and total cost of care over the first 30 days after discharge. Results: Patients managed with early ID involvement had shorter length of stay, lower spending, and lower mortality in the index stay than those patients managed without ID involvement. Relative to late, early ID involvement was associated with shorter length of stay and lower cost. Individuals with early ID intervention during hospitalization had fewer readmissions and lower healthcare payments after discharge. Relative to late, those with early ID intervention experienced lower readmission, lower spending, and lower mortality. Conclusions: Among privately insured patients less than 65 years old, treated in a hospital, early intervention with an ID physician was associated with lower mortality rate and shorter length of stay. Patients who received early ID intervention during their hospital stay were less likely to be readmitted after discharge and had lower total healthcare spending.

Essential Resources and Strategies for Antibiotic Stewardship Programs in the Acute Care Setting.

Background: Antibiotic stewardship programs improve clinical outcomes and patient safety and help combat antibiotic resistance. Specific guidance on resources needed to structure stewardship programs is lacking. This manuscript describes results of a survey of US stewardship programs and resultant recommendations regarding potential staffing structures in the acute care setting. Methods: A cross-sectional survey of members of 3 infectious diseases subspecialty societies actively involved in antibiotic stewardship was conducted. Survey responses were analyzed with descriptive statistics. Logistic regression models were used to investigate the relationship between stewardship program staffing levels and self-reported effectiveness and to determine which strategies mediate effectiveness. Results: Two-hundred forty-four respondents from a variety of acute care settings completed the survey. Prior authorization for select antibiotics, antibiotic reviews with prospective audit and feedback, and guideline development were common strategies. Eighty-five percent of surveyed programs demonstrated effectiveness in at least 1 outcome in the prior 2 years. Each 0.50 increase in pharmacist and physician full-time equivalent (FTE) support predicted a 1.48-fold increase in the odds of demonstrating effectiveness. The effect was mediated by the ability to perform prospective audit and feedback. Most programs noted significant barriers to success. Conclusions: Based on our survey's results, we propose an FTE-to-bed ratio that can be used as a starting point to guide discussions regarding necessary resources for antibiotic stewardship programs with executive leadership. Prospective audit and feedback should be the cornerstone of stewardship programs, and both physician leadership and pharmacists with expertise in stewardship are crucial for success.

DISC: Describing Infections of the Spine treated with Ceftaroline.

OBJECTIVES: Infections of the spine lead to considerable morbidity and a high cost to the global healthcare system. Currently, evidence for using ceftaroline, an advanced-generation cephalosporin active against methicillin-resistant Staphylococcus aureus (MRSA), in spine infections is limited. METHODS: Describing Infections of the Spine treated with Ceftaroline (DISC) is a multicentre, retrospective, cohort study that evaluated ceftaroline for treating spine infections. Patients were included if they were aged ≥18 years, diagnosed with a spine infection and treated with ceftaroline for ≥28 days. A control group was identified with the same inclusion criteria as the study population except they were treated with a comparator antibiotic for ≥28 days. RESULTS: Thirty-seven patients were included each in the ceftaroline and control groups. MRSA was the most commonly identified pathogen. With no differences between groups in age, sex, race or co-morbidities (with the exception of chronic kidney disease), treatment with ceftaroline led to similar clinical success compared with the control group. Multivariate regression analysis did not show a significant difference between the two groups in terms of clinical success after controlling for other covariates (adjusted odds ratio=1.49; P=0.711). More patients who received ceftaroline were discharged to an extended-care or rehabilitation facility than home compared with controls (81% vs. 54%, respectively; P=0.024). Side effects and toxicities were rare, including one case of eosinophilic pneumonia in the ceftaroline group. CONCLUSIONS: Ceftaroline appears to be a safe and effective therapy for infections of the spine, including from MRSA.

Tedizolid: The First Once-Daily Oxazolidinone Class Antibiotic.

Tedizolid phosphate is the second commercially available oxazolidinone antibiotic, although the first one in class that is dosed once daily. It is a prodrug that is rapidly converted to the active compound tedizolid. Tedizolid has activity against a wide range of gram-positive pathogens, including methicillin-resistant Staphylococcus aureus. It is approved to treat acute bacterial skin and skin structure infections (ABSSSIs). In 2 randomized controlled phase 3 trials, 6 days of tedizolid (200 mg once daily) has been proven to be noninferior to 10 days of linezolid (600 mg twice daily). These 2 ABSSSI studies have positioned tedizolid among the growing armamentarium of newer, novel, anti-gram-positive agents. Tedizolid appears to differ from linezolid in the incidence of gastrointestinal and hematologic side effects and appears to lack drug interactions with selective serotonin reuptake inhibitors. Conditions other than ABSSSI are currently being evaluated in clinical studies.

Histoplasmosis complicating tumor necrosis factor-α blocker therapy: a retrospective analysis of 98 cases.

BACKGROUND: Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. METHODS: We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. RESULTS: The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. CONCLUSIONS: In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.

Dosing strategy to allow continued therapy with daptomycin after asymptomatic increases in creatine kinase levels.

PURPOSE: A case series in which a novel dosing strategy for managing mild, asymptomatic creatine kinase (CK) increases associated with daptomycin therapy is presented. SUMMARY: Eight patients received a mean daptomycin dosage of 7.75 mg/kg/day for a median duration of 42 days. Seven of the eight patients were being treated for a bone and joint infection, and all but one had methicillin-resistant Staphylococcus aureus. All patients had asymptomatic increases in CK concentrations during daptomycin therapy (peak range, 400-1200 IU/L). A single daptomycin dose was withheld from each patient, and therapy was resumed 24 hours later, most often at the same dosage. The elevated CK values in these patients resolved, and all patients were able to complete daptomycin therapy without further increases in CK elevations. These findings indicate that withholding one dose of daptomycin during treatment may allow patients with asymptomatic, elevated CK concentrations to continue therapy with CK level normalization. Although the mechanism of daptomycin-mediated muscle injury is not fully understood, a reduction in daptomycin exposure via a one-dose cessation of therapy may allow for physiological restoration of sarcolemma membrane integrity that may be disrupted by daptomycin in individuals exhibiting CK elevation. CONCLUSION: A single daptomycin dose was withheld from eight patients with asymptomatic increases in serum CK concentrations, then daptomycin therapy was resumed 24 hours later, most often at the previous dosage. The CK concentrations returned to normal, and all patients were able to complete daptomycin therapy without further increases in CK concentrations.

Histoplasmosis after solid organ transplant.

BACKGROUND: To improve our understanding of risk factors, management, diagnosis, and outcomes associated with histoplasmosis after solid organ transplant (SOT), we report a large series of histoplasmosis occurring after SOT. METHODS: All cases of histoplasmosis in SOT recipients diagnosed between 1 January 2003 and 31 December 2010 at 24 institutions were identified. Demographic, clinical, and laboratory data were collected. RESULTS: One hundred fifty-two cases were identified: kidney (51%), liver (16%), kidney/pancreas (14%), heart (9%), lung (5%), pancreas (2%), and other (2%). The median time from transplant to diagnosis was 27 months, but 34% were diagnosed in the first year after transplant. Twenty-eight percent of patients had severe disease (requiring intensive care unit admission); 81% had disseminated disease. Urine Histoplasma antigen detection was the most sensitive diagnostic method, positive in 132 of 142 patients (93%). An amphotericin formulation was administered initially to 73% of patients for a median duration of 2 weeks; step-down therapy with an azole was continued for a median duration of 12 months. Ten percent of patients died due to histoplasmosis with 72% of deaths occurring in the first month after diagnosis; older age and severe disease were risk factors for death from histoplasmosis. Relapse occurred in 6% of patients. CONCLUSIONS: Although late cases occur, the first year after SOT is the period of highest risk for histoplasmosis. In patients who survive the first month after diagnosis, treatment with an amphotericin formulation followed by an azole for 12 months is usually successful, with only rare relapse.

Ceftaroline-induced eosinophilic pneumonia.

We present a case of eosinophilic pneumonia due to ceftaroline used for the treatment of methicillin-resistant Staphylococcus aureus bacteremia associated with a postoperative spinal infection. Our patient developed shortness of breath and hypoxemia on the fifth week of ceftaroline therapy. Chest imaging disclosed diffuse bilateral infiltrates. Laboratory abnormalities included peripheral eosinophilia and eosinophilic predominant bronchoalveolar lavage fluid. The combination of ceftaroline discontinuation plus initiation of steroid treatment resulted in complete resolution of signs, symptoms, and radiologic abnormalities. We speculate about possible mechanisms underlying this adverse event and diagnostic criteria for drug-induced eosinophilic pneumonia.

Mobile infectious disease references: from the bedside to the beach.

Point-of-care access to current medical information is easily available to the practitioner through the use of smartphones, iPads, and other personal digital assistants. There are numerous mobile applications (apps) that provide easy-to-use and often well-referenced medical guidance for the infectious diseases practitioner. We reviewed 6 commonly utilized mobile apps available for handheld devices: the Emergency Medicine Residents' Association's (EMRA's) Antibiotic Guide, Epocrates Deluxe, Johns Hopkins Antibiotic Guide, Sanford Guide, the Medscape mobile app, and the Infectious Diseases Compendium. We evaluated several basic infectious diseases topics (including but not limited to endocarditis, vancomycin, and Acinetobacter infection) and attempted to objectively score them for metrics that would help the provider determine which mobile app would be most useful for his or her practice. The Johns Hopkins Antibiotic Guide and the Sanford Guide had the highest cumulative scores, whereas EMRA scored the lowest. We found that no single app will meet all of the needs of an infectious diseases physician. Each app delivers content in a unique way and would meet divergent needs for all practitioners, from the experienced clinician to the trainee. The ability to rapidly access trusted medical knowledge at the point of care can help all healthcare providers better treat their patients' infections.

Staphylococcus aureus pyomyositis compared with non-Staphylococcus aureus pyomyositis.

OBJECTIVES: Pyomyositis is an acute bacterial infection of skeletal muscle not arising from contiguous infection. It is often hematogenous in origin and typically associated with abscess formation. Our objective was to determine if there were any differences in the clinical presentation of disease between Staphylococcus aureus (SA) and non-Staphylococcus aureus pyomyositis. We also sought to determine if methicillin-resistant SA (MRSA) occurred more frequently during the final years of the study period. METHODS: A retrospective chart review study at three institutions in two cities. RESULTS: Sixty cases of pyomyositis were identified between 1990 and 2010. Twenty-nine patients were infected with SA while 31 had other bacterial etiologies or were culture negative. Those with a traumatic event prior to the onset of infection were more likely to have a SA infection while SA infected patients were younger. Our first documented case of MRSA occurred in 2005, but the frequency of MRSA infection remained static over the following five years. CONCLUSIONS: Pyomyositis is an emerging infection that is underappreciated by many physicians. While MRSA has emerged as the foremost cause of SA infections in a majority of clinical conditions, in this series most patients still had methicillin-sensitive SA as their cause of pyomyositis. In light of the severity of pyomyositis and the potential for bacteremia (either as a source or complication of the infection), empiric SA therapy should be initiated in all patients until the culture results are available.

Staphylococcus aureus bacteremia (SAB) with associated S. aureus bacteriuria (SABU) as a predictor of complications and mortality.

BACKGROUND AND OBJECTIVES: Staphylococcus aureus (SA) bacteremia (SAB) is associated with a high rate of complications, most of which are related to hematogenous seeding into deep tissues or prosthetic material. SA bacteriuria (SABU) has been described in association with SAB, but has not been evaluated as a predictor for complicated bacteremia, which was the objective of our study. METHODS (DESIGN, SETTING, AND PATIENTS): We conducted a retrospective study of patients admitted to the hospital with SAB. The 118 patients included in the study were divided in 2 cohorts: a group with SABU and a group without SA in the urine. We followed the 2 cohorts for an average of 8 months and evaluated the differences in complications and mortality. RESULTS: SABU was found in 28 of 118 patients with SAB. Eighteen patients (64%) in this group had complications from the bacteremia, while in the group without SABU only 33% (30/90 patients) had complications (P = 0.004). The SABU group also had more deaths (32% vs. 14%; P = 0.036). CONCLUSIONS: In this population of hospitalized patients with SAB, the presence of SABU was associated with an increased risk of early complications, including septic shock, and with higher mortality. A routine urine culture in search of SABU may be a helpful tool for detection of those patients with SAB who are at increased risk of complications and death.

Chronic ulceration from Mycobacterium marinum infection and the diagnostic value of T-cell interferon-gamma release assays.

This case report describes the differential diagnosis of cutaneous ulcerations and the utility of the interferon-gamma release assays as a tool to aid in the diagnosis. These new assays can be used to identify mycobacterial infections (specifically Mycobacterium marinum) as the etiologic agents.

Daptomycin for methicillin-resistant Staphylococcus aureus infections of the spine.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection is increasingly common. Treatment with vancomycin-based therapy is often unsuccessful. Daptomycin is a relatively new lipopeptide antibiotic with potent activity against MRSA. PURPOSE: To describe the successful management of MRSA infection involving the spine. STUDY DESIGN: Two case reports of MRSA infection, one involving epidural and lumbar subdural abscesses, the other with osteomyelitis and discitis. METHODS: Two cases are described, one with lumbar epidural and subdural abscesses and the other with osteomyelitis and discitis of the spine. Switching from vancomycin to daptomycin plus rifampin-based therapy resulted in patient improvement that allowed discharge from the hospital. RESULTS: Both patients recovered fully from their infection. CONCLUSIONS: Daptomycin is a safe and effective option for the treatment of MRSA infection involving the spine.

Surfing the web: practicing medicine in a technological age: using smartphones in clinical practice.

Mobile technology has the potential to revolutionize how physicians practice medicine. From having access to the latest medical research at the point of care to being able to communicate at a moment's notice with physicians and colleagues around the world, we are practicing medicine in a technological age. During recent years, many physicians have been simultaneously using a pager, cellular telephone, and personal digital assistant (PDA) to keep in communication with the hospital and to access medical information or calendar functions. Many physicians have begun replacing multiple devices with a "smartphone," which functions as a cellular telephone, pager, and PDA. The goal of this article is to provide an overview of the currently available platforms that make up the smartphone devices and the available medical software. Each platform has its unique advantages and disadvantages, and available software will vary by device and is in constant flux.