Risk factors for readmission in patients discharged with outpatient parenteral antimicrobial therapy: a retrospective cohort study.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) is a practical and effective way of delivering antimicrobial therapy, but may be associated with significant risk for hospital readmission. This study aimed to elucidate risk factors related to 30-day readmissions in patients who were discharged with OPAT at Mount Sinai Beth Israel (MSBI). METHODS: This IRB approved retrospective cohort study included patients who were at least 18 years or older, admitted to MSBI from August 2015 to March 2016, and discharged to receive OPAT. Patients with intravenous antibiotics prescribed for chronic suppression or planned readmission within 30 days were excluded. The main outcome was readmission to the hospital within 30 days from previous hospital discharge. Univariate and logistic regression analyses were performed to determine predictors of 30-day readmission. RESULTS: There were a total of 200 patients included in the analysis; the median age was 60 years, 65.5% were male, and the median Charlson score was 2. A total of 155 (78%) patients received a peripherally inserted central catheter (PICC); the remainder was discharged with a midline. The most common medications prescribed for OPAT included cephalosporins (41%), vancomycin (31%), carbapenems (23%), and penicillins (16%). A total of 42 patients (21%) were readmitted within 30 days after previous discharge. Discharge to a skilled nursing facility or subacute rehabilitation center was found to be an independent predictor of readmission on logistic regression analyses (p <  0.05). CONCLUSION: Readmissions are common in patients discharged with OPAT. Recognizing predictors of readmission may help determine strategies to optimize care.

Combination Therapy With Vancomycin and Ceftaroline for Refractory Methicillin-resistant Staphylococcus aureus Bacteremia: A Case Series.

PURPOSE: Although vancomycin has been the mainstay of therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections, its effectiveness has been challenged. Combination therapy may be used for patients with persistent MRSA bacteremia refractory to initial therapy. Studies have reported in vitro synergy between vancomycin and ceftaroline; however, clinical experience with this therapy is limited. Here, we report our experience with 5 cases of vancomycin-refractory MRSA bacteremia treated with the combination of vancomycin and ceftaroline. METHODS: Between January 2014 and August 2016, 5 patients were identified who received vancomycin and ceftaroline combination therapy due to persistent bacteremia or deterioration of their clinical status on vancomycin alone (despite a vancomycin MIC within the susceptible range). FINDINGS: Five patients presented with MRSA bacteremia secondary to endocarditis (n = 2), epidural abscess (n = 2), or left iliopsoas abscess (n = 1). Four of the 5 patients experienced microbiologic cure, and 1 patient transitioned to palliative care. IMPLICATIONS: This case series serves to describe additional clinical experience with vancomycin and ceftaroline combination therapy. This combination may be considered when vancomycin monotherapy does not lead to microbiological and/or clinical improvement in patients with metastatic MRSA bacteremia. Additional studies are warranted to further define its role in salvage therapy for persistent MRSA bacteremia.

A Survey of Pharmacists in Academia on the Current Practice of Estimation of Kidney Function for Antimicrobial Dosing in Adults.

PURPOSE: To determine the methods used by pharmacists in academia to estimate kidney function for antimicrobial dosing. METHODS: Stratified by region, a random sample of Accreditation Council for Pharmacy Education recognized Colleges of Pharmacy was selected for a total of 40 programs. Identified college Web sites were reviewed for eligible participants using the predefined inclusion/exclusion criteria. This was used to create a sampling frame from which 30% and 20% of faculty were randomly chosen and invited to participate via e-mail and mail-administered surveys, respectively. RESULTS: Of the responders, 86% (31 of 36) who routinely estimate kidney function utilized the Cockcroft-Gault (CG) equation. In obese patients, 75% utilized the CG equation with or without adjustments. In patients ≥65 years, 42% adjusted serum creatinine to 1 mg/dL and 25% did not make any modifications. The majority of the responders accounted for patients with quadripalegia or bed-bound patients when estimating kidney function. In scenario examples, 51% (18 of 35) dosed an elderly female and 51% (18 of 35) a morbidly obese female as creatinine clearance ≥50 mL/min; however, 49% (17 of 35) did not. CONCLUSION: The majority of responders utilized the CG equation for estimating kidney function with or without adjustments. Although a number of consistencies were noted, discrepancies existed, especially with elderly and obese patients.

Fluoroquinolone- and ceftriaxone-based therapy of community-acquired pneumonia in hospitalized patients: the risk of subsequent isolation of multidrug-resistant organisms.

A retrospective cohort study was performed on 175 adult patients treated for community-acquired pneumonia with moxifloxacin or ceftriaxone/azithromycin in a nonintensive care unit. Both cohorts were very similar with regard to a wide range of characteristics including age, severity of disease, comorbidities, length of stay, and mortality. Multidrug-resistant organisms were subsequently isolated from 6 (15%) moxifloxacin-treated patients and 5 (4%) ceftriaxone/azithromycin-treated patients within 90 days after beginning of therapy (P = .026 on logistic regression analysis).

Nested case-control study of the emergence of tigecycline resistance in multidrug-resistant Klebsiella pneumoniae.

We performed a nested case-control study (ratio of 1:4) on the emergence of tigecycline-resistant multidrug-resistant Klebsiella pneumoniae (TR-MDRKP) isolates among patients who initially presented with a tigecycline-susceptible MDRKP isolate. Out of 260 patients, 24 (9%) had a subsequent clinical culture positive for a TR-MDRKP isolate within the 90-day follow-up period. On logistic regression analyses, receipt of tigecycline (adjusted odds ratio [OR], 5.06; 95% confidence interval [CI], 1.80 to 14.23; P = 0.002) was the only independent predictor of subsequent isolation of a TR strain.

Methicillin-susceptible Staphylococcus aureus nasal colonization and the risk of subsequent methicillin-resistant Staphylococcus aureus infections among hospitalized patients.

Few data exist on the risk of methicillin-resistant Staphylococcus aureus (MRSA) infections among known methicillin-susceptible S. aureus (MSSA) carriers. In a cohort of 2991 hospitalized MSSA carriers, 22 (22%) of 98 S. aureus infections that occurred within a subsequent 6-month period were caused by MRSA. Recent fluoroquinolone use was an independent predictor of MRSA infections (P < .001).

Impact of results of methicillin-resistant Staphylococcus aureus surveillance culture of nasal specimens on subsequent antibiotic prescribing patterns.

We studied the potential impact of results of methicillin-resistant Staphylococcus aureus (MRSA) surveillance culture of nasal specimens on physicians' vancomycin-prescribing habits. We compared 116 case patients who had positive results with 116 matched control subjects who had negative results. On multivariate analyses, a positive MRSA carrier status remained strongly predictive of vancomycin use within the subsequent 12 weeks.

Minocycline modulates neuroinflammation independently of its antimicrobial activity in staphylococcus aureus-induced brain abscess.

Minocycline exerts beneficial immune modulatory effects in several noninfectious neurodegenerative disease models; however, its potential to influence the host immune response during central nervous system bacterial infections, such as brain abscess, has not yet been investigated. Using a minocycline-resistant strain of Staphylococcus aureus to dissect the antibiotic's bacteriostatic versus immune modulatory effects in a mouse experimental brain abscess model, we found that minocycline significantly reduced mortality rates within the first 24 hours following bacterial exposure. This protection was associated with a transient decrease in the expression of several proinflammatory mediators, including interleukin-1beta and CCL2 (MCP-1). Minocycline was also capable of protecting the brain parenchyma from necrotic damage as evident by significantly smaller abscesses in minocycline-treated mice. In addition, minocycline exerted anti-inflammatory effects when administered as late as 3 days following S. aureus infection, which correlated with a significant decrease in brain abscess size. Finally, minocycline was capable of partially attenuating S. aureus-dependent microglial and astrocyte activation. Therefore, minocycline may afford additional therapeutic benefits extending beyond its antimicrobial activity for the treatment of central nervous system infectious diseases typified by a pathogenic inflammatory component through its ability to balance beneficial versus detrimental inflammation.

Tetracyclines as an oral treatment option for patients with community onset skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus.

Few data exist on the clinical utility of the expanded-spectrum tetracyclines doxycycline and minocycline for the treatment of community-associated methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTI). We performed a retrospective cohort study of 276 patients who presented with 282 episodes of MRSA SSTI to the emergency room or outpatient clinic at two tertiary medical centers between October 2002 and February 2007. The median percentage of patients infected with MRSA strains that were susceptible to tetracycline was 95%. Time zero was defined as the time of the first incision and drainage procedure or, if none was performed, the time of the first positive wound culture. The median patient age was 48 years. Abscesses constituted the majority of clinical presentations (75%), followed by furuncles or carbuncles (13%) and cellulitis originating from a purulent focus of infection (12%). A total of 225 patients (80%) underwent incision and drainage. Doxycycline or minocycline was administered in 90 episodes (32%); the other 192 SSTI were treated with beta-lactams. Treatment failure, defined as the need for a second incision and drainage procedure and/or admission to the hospital within at least 2 days after time zero, was diagnosed in 28 episodes (10%) at a median of 3 days after time zero. On logistic regression analysis, receipt of a beta-lactam agent was the only clinical characteristic associated with treatment failure (adjusted odds ratio, 3.94; 95% confidence interval, 1.28 to 12.15; P = 0.02). The expanded-spectrum tetracyclines appear to be a reasonable oral treatment option for patients with community onset MRSA SSTI in areas where MRSA strains are susceptible to the tetracyclines.

Community-onset methicillin-resistant Staphylococcus aureus skin and soft-tissue infections: impact of antimicrobial therapy on outcome.

BACKGROUND: Conflicting data exist on the role of antimicrobial therapy for the treatment of uncomplicated community-onset methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infections (SSTIs). METHODS: We performed a retrospective cohort study of 492 adult patients with 531 independent episodes of community-onset MRSA SSTIs, which consisted of abscesses, furuncles/carbuncles, and cellulitis, at 2 tertiary care medical centers. The purpose of the study was to determine the impact of active antimicrobial therapy (i.e., the use of an agent to which the organism is susceptible) and other potential risk factors on the outcome for patients with uncomplicated community-onset MRSA SSTIs. Treatment failure was the primary outcome of interest and was defined as worsening signs of infection associated with microbiological and/or therapeutic indicators of an unsuccessful outcome. Bivariate analyses and logistic regression analyses were preformed to determine predictors of treatment failure. RESULTS: An incision and drainage procedure was performed for the majority of patients. Treatment failure occurred in 45 (8%) of 531 episodes of community-onset MRSA SSTI. Therapy was successful for 296 (95%) of 312 patients who received an active antibiotic, compared with 190 (87%) of 219 of those who did not (P=.001 in bivariate analysis). Use of an inactive antimicrobial agent was an independent predictor of treatment failure on logistic regression analysis (adjusted odds ratio, 2.80; 95% confidence interval, 1.26-6.22; P=.01). CONCLUSIONS: Our findings suggest that certain patients with SSTIs that are likely caused by MRSA would benefit from treatment with an antimicrobial agent with activity against this organism.

Use of long-acting tetracyclines for methicillin-resistant Staphylococcus aureus infections: case series and review of the literature.

BACKGROUND: Few data exist on the efficacy of the long-acting tetracyclines doxycycline and minocycline against methicillin-resistant Staphylococcus aureus (MRSA) infection. METHODS: The medical records of 24 patients with serious tetracycline-susceptible MRSA infections who were treated with doxycycline or minocycline were reviewed. A review of the literature on the use of these antibiotics for treatment of both methicillin-susceptible and methicillin-resistant S. aureus infection was also performed. RESULTS: Complicated skin and skin-structure infections were most common (67%). Clinical cure was achieved in 20 (83%) of 24 patients in our case series. Both drugs were well-tolerated. The review of the literature on a total of 85 patients with S. aureus infection revealed similar results. CONCLUSIONS: Long-acting tetracyclines may be a reasonable treatment alternative for patients with certain types of MRSA infection.

High-level penicillin-nonsusceptible Streptococcus pneumoniae bacteremia: identification of a low-risk subgroup.

High-level penicillin resistance has been associated with treatment failure in patients with Streptococcus pneumoniae infections. To identify a subgroup of patients at low risk for high-level penicillin-nonsusceptible S. pneumoniae bacteremia, a cross-sectional study of 303 patients was performed. For the total study population, penicillin resistance was observed in 98 (32%) of 303 patients; high-level resistance was seen in 33 (11%). A predictive model was created by using 3 baseline variables that were independently associated with high-level penicillin resistance: previous beta -lactam antibiotic use, previous stay in a risk area (defined as stay in day care facilities, prisons, homeless shelters, nursing homes, or other long-term care facilities), and previous respiratory tract infection. The model was used to identify patients at low and high risk for high-level penicillin-resistant pneumococcal bacteremia. None of the isolates of patients in the low-risk subgroup had ceftriaxone resistance. Patients in the low-risk subgroup could be empirically treated with fluoroquinolone-sparing regimens.

Streptococcus pneumoniae bacteremia: duration of previous antibiotic use and association with penicillin resistance.

Previous antibiotic exposure is one of the most important predictors for acquisition of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) infection. To determine the impact of duration of exposure to different antibiotic classes, a study of 303 patients with S. pneumoniae bacteremia was undertaken. Ninety-eight cases of bacteremia (32%) were caused by a penicillin-nonsusceptible isolate. Bivariate analysis revealed that use of beta-lactams, sulfonamides, and macrolides within the last 1 and 6 months before presentation was associated with PNSP bacteremia (P<.05). Fluoroquinolone consumption was not related to bacteremia due to PNSP (P>.1). Both short- and long-term beta-lactam use significantly increased the risk for PNSP infection. Logistic regression analysis revealed that use of beta-lactams and macrolides in the 6 months before the first positive blood culture result were independent risk factors (P<.05). Risk for acquiring PNSP infection depends on both the class of antibiotic to which the patient was exposed and the duration of therapy.