Kelly Echevarria

Comparison of Cefazolin versus Oxacillin for Treatment of Complicated Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus

ABSTRACT Contrary to prior case reports that described occasional clinical failures with cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infections, recent studies have demonstrated no difference in outcomes between cefazolin and antistaphylococcal penicillins for the treatment of MSSA bacteremia. While promising, these studies described low frequencies of high-inoculum infections, such as endocarditis. This retrospective study compares clinical outcomes of cefazolin versus oxacillin for complicated MSSA bacteremia at two tertiary care hospitals between January 2008 and June 2012. Fifty-nine patients treated with cefazolin and 34 patients treated with oxacillin were included. Osteoarticular (41%) and endovascular (20%) sources were the predominant sites of infection. The rates of clinical cure at the end of therapy were similar between cefazolin and oxacillin (95% versus 88%; P = 0.25), but overall failure at 90 days was higher in the oxacillin arm (47% versus 24%; P = 0.04). Failures were more likely to have received surgical interventions (63% versus 40%; P = 0.05) and to have an osteoarticular source (57% versus 33%; P = 0.04). Failures also had a longer duration of bacteremia (7 versus 3 days; P = 0.0002), which was the only predictor of failure. Antibiotic selection was not predictive of failure. Rates of adverse drug events were higher in the oxacillin arm (30% versus 3%; P = 0.0006), and oxacillin was more frequently discontinued due to adverse drug events (21% versus 3%; P = 0.01). Cefazolin appears similar to oxacillin for the treatment of complicated MSSA bacteremia but with significantly improved safety. The higher rates of failure with oxacillin may have been confounded by other patient factors and warrant further investigation.

Community-Associated Methicillin-Resistant Staphylococcus Aureus: New Bug, Old Drugs

Objective: To discuss community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections and evaluate older antibiotics as suitable therapeutic treatment options. Data Sources: Searches of MEDLINE, EMBASE, and the Cochrane Library (1966–May 2006) were performed using the key terms methicillin resistance, community-acquired, community associated, treatment, Staphylococcus aureus, mec, and Panton-Valentine leukocidin. Study Selection and Data Extraction: All articles were critically evaluated and all relevant information was included in this review. Data Synthesis: There has been a documented shift of methicillin resistance occurring in staphylococcal infections manifested within the community. Infections caused by CA-MRSA possess unique characteristics including lack of hospital-associated risk factors, improved susceptibility patterns, distinct genotypes, faster doubling times, and additional toxins. Potential therapeutic options to treat these infections include trimethoprim/sulfamethoxazole (TMP/SMX), clindamycin, tetracyclines, fluoroquinolones, and new antimicrobials. Conclusions: CA-MRSA infections can be successfully treated with older, oral antibiotic agents including TMP/SMX, clindamycin, and tetracyclines. Fluoroquinolones and linezolid should be avoided as first-line agents.

Monotherapy or combination therapy? The Pseudomonas aeruginosa conundrum.

The use of combination antibiotic therapy for severe pseudomonal infections is a standard practice in many hospitals; however, the data supporting its use are somewhat unclear. Possible benefits of combination therapy for Pseudomonas aeruginosa infections include in vitro antibiotic synergy, prevention of the emergence of bacterial resistance while receiving therapy, and improved adequacy of empiric therapy. Unfortunately, the potential disadvantages are also considerable, the most worrisome of which are drug toxicity and creation of multidrug‐resistant organisms in the environment. Many in vitro and animal studies have attempted to shed light on this clinically challenging issue; however, these studies have often yielded conflicting results and used different study methods, which limits the clinical utility of the results. Clinical studies have also attempted to clarify this issue, particularly in patients with serious pseudomonal infections such as bacteremia and ventilator‐associated pneumonia, but again, often resulted in conflicting conclusions. Thus, we performed a MEDLINE search (1950‐May 2010) of clinical and in vitro studies evaluating the use of antibiotic combination therapy and monotherapy for bacteremia and pneumonia due to P. aeruginosa. Although a clear answer still eludes this controversy, combination therapy for seriously ill patients suspected of having pseudomonal infection has been shown, with considerable evidence, to improve the likelihood of an active agent being included in the initial antibiotic regimen of these patients. The clinical status of the patient and true likelihood of encountering a multidrug‐resistant organism should be evaluated before deciding on empiric combination therapy. Future research may be able to better identify which patient populations might receive the most benefit from combination therapy rather than using combination therapy for everyone at risk for these infections.

Clinical Predictors and Risk Factors for Relapsing Clostridium difficile Infection

Background:Clostridium difficile infection (CDI) is a common cause of morbidity among hospitalized patients. Multiple factors have been associated with primary CDI, but risk factors for CDI relapses are less well described. Methods:This was a retrospective cohort study of patients with CDI over a 15-month period. We compared patients with relapsing and nonrelapsing CDI, including risk factors associated with primary CDI and other variables hypothesized to be associated with relapsing CDI and 90-day mortality. Multivariable logistic regression models were created to examine risk factors for relapse and 90-day mortality. Results:One hundred twenty-nine consecutive patients with CDI were included; 38 (29%) had relapsing CDI. Factors associated with relapsing CDI included fluoroquinolone use (71% versus 49%, P = 0.04) and incidence of stroke (29% versus 12%, P = 0.02). In a regression model, use of a fluoroquinolone was associated with relapsing CDI (OR = 2.52, 95% CI = 1.11–5.72). Factors associated with 90-day mortality included higher Charlson comorbidity index score (4.34 ± 1.71 versus 3.42 ± 2.08, P = 0.02), severe CDI (58% versus 32%, P = 0.01), and the use of piperacillin/tazobactam (45% versus 23%, P = 0.03) or meropenem (10% versus 1%, P = 0.04). In the regression analysis, 90-day mortality was associated with severe CDI (OR = 1.76; 95% CI = 1.19–2.59). Conclusion:Fluoroquinolone use and prior stroke are associated with an increased risk of relapsing CDI. Relapsing CDI and severe CDI are both associated with increased 90-day mortality.

Breakthrough Bacteremia and Septic Shock Due to Streptococcus anginosus Resistant to Daptomycin in a Patient Receiving Daptomycin Therapy

Daptomycin is active against many Gram-positive pathogens, including multidrug-resistant organisms ([3][1]). Elevated daptomycin MICs have been associated with clinical and microbiologic failures in Staphylococcus aureus and Enterococcus infections ([7][2], [8][3]). The current Clinical and

Clinical evaluation of the role of ceftaroline in the management of community acquired bacterial pneumonia

Ceftaroline fosamil (ceftaroline) was recently approved for the treatment of community- acquired pneumonia (CAP) and complicated skin infections. This newly developed cephalosporin possesses a broad spectrum of activity against gram-positive and gram-negative bacteria. Most importantly, ceftaroline demonstrates potent in vitro antimicrobial activity against multi-drug resistant Streptococcus pneumoniae and methicillin-resistant strains of Staphylococcus aureus. In two Phase III, double-blinded, randomized, prospective trials (FOCUS 1 and FOCUS 2), ceftaroline was shown to be non-inferior to ceftriaxone for the treatment of CAP in hospitalized patients. Ceftaroline exhibits low resistance rates and a safety profile similar to that of other cephalosporins. In this review, we will evaluate the pharmacological characteristics, safety, antimicrobial properties, and efficacy of ceftaroline and its applications in the treatment of CAP.

Efficacy and safety of cefepime

A Review by Dafna Yahav and colleagues found that cefepime compared with other beta-lactam antibiotics was associated with increased all-cause mortality, a diff erence driven by the febrile neutropenia subset of patients (risk ratio [RR] 1·26, 95% CI 1·08–1·49). To better understand these diff erences and to determine if infectious or non-infectious causes impacted the mortality results, we reviewed the 19 studies comprising the neutropenic fever subset of these data. Whenever possible, the actual articles were obtained from the FDA website or through medical library holdings. Where abstracts were the only information available or data within the published literature were not adequate to answer all questions, every attempt was made to contact the original authors. Studies were specifi cally reviewed for data including number of deaths in each arm and causes of death. For these 19 studies, complete cause of death information was obtained for 11 and partial cause of death information for two. These 13 studies included 64% of the all-cause neutropenic deaths in Yahav and colleagues’ paper. Review of causes of death among these patients found no marked diff erences between cefepime and beta-lactam comparator for any infectious cause (table 1). A higher proportion of patients died secondary to progression of their underlying disease in the cefepime arm compared with the other beta-lactam arm. Furthermore, no patients were determined to have died directly as a result of receiving therapy with any agent, including cefepime (references 2–14, and personal communication with the lead author of reference 4). investigation (fi gure 1) and 0·85 (0·81–0·89, I=95·6%) for passive case fi nding. Restricting pooled analysis to confi rmed active tuberculosis, the pooled estimates would be 0·08 (0·05–0·12, I=93.5%) for household contact investigation and 0·92 (0·88–0·95, I=93·5%) for passive case fi nding. Such fi ndings may highlight the key role of passive case fi nding in the control of tuberculosis. The public-health impact of household contact investigation is expected to be sustantially lower than that of passive case fi nding. The incubation period of tuberculosis varies from a few weeks to a few decades and household contact investigation focuses on examination at only one point of time. Additionally, most infected hosts do not develop disease. Thus, it may be more cost eff ective for low-income and middle-income countries to spend limited public-health resources on improving accessibility of a patient-friendly health-care infrastructure and on increasing public awareness of tuberculosis, upon which passive case fi nding heavily relies. The feasibility of achieving the case detection target of 70% by passive case fi nding has been substantiated by early studies in India, which showed that 70% of people with smear-positive tuberculosis had symptoms and sought health care. In conclusion, although household contact investigation may be considered in low tuberculosis incidence, high-income countries, the available evidence from meta-analysis does not favour household contact investigation in low-income and middleincome countries. The importance of improving case detection among symptomatic patients self-reporting to health services cannot be over-emphasised.

Prophylactic Acid-Suppressive Therapy in Hospitalized Adults: Indications, Benefits, and Infectious Complications

&NA; Acid‐suppressive therapy for prophylaxis of stress ulcer bleeding is commonly prescribed for hospitalized patients. Although its use in select, at‐risk patients may reduce clinically significant gastrointestinal bleeding, the alteration in gastric pH and composition may place these patients at a higher risk of infection. Although any pharmacologic alteration of the gastric pH and composition is associated with an increased risk of infection, the risk appears to be highest with proton pump inhibitors, perhaps owing to the potency of this class of drugs in increasing the gastric pH. With the increased risk of infection, universal provision of pharmacologic acid suppression to all hospitalized patients, even all critically ill patients, is inappropriate and should be confined to patients meeting specific criteria. Nurses providing care in critical care areas may be instrumental in screening for appropriate use of acid‐suppressive therapy and ensuring the drugs are discontinued upon transfer out of intensive care or when risk factors are no longer present. CE 1.0 hour, Pharma 0.75, CERP A This article has been designated for CE contact hour(s). The evaluation tests your knowledge of the following objectives: 1. Identify evidence‐based indications for stress ulcer bleeding prophylaxis in both critically ill and noncritically ill patients 2. Discuss the infectious risks associated with acid‐suppressive therapy, including pneumonia and Clostridium difficile‐associated diarrhea 3. Develop evidence‐based criteria for use and discontinuation of acid‐suppressive therapy To complete evaluation for CE contact hour(s) for activity #C1733, visit www.ccnonline.org and click the “CE Articles” button. No fee for AACN members. This CE activity expires on June 1, 2019. The American Association of Critical‐Care Nurses is an accredited provider of continuing nursing education by the American Nurses Credentialing Centers Commission on Accreditation. AACN has been approved as a provider of continuing education in nursing by the State Boards of Registered Nursing of California (#01036) and Louisiana (#LSBN12).

Managing community acquired pneumonia in the elderly – the next generation of pharmacotherapy on the horizon

ABSTRACT Introduction: Community acquired pneumonia (CAP) is associated with high rates of morbidity and mortality, especially among the elderly. Antibiotic treatment for CAP in the elderly is particularly challenging for many reasons, including compliance issues, immunosuppression, polypharmacy and antimicrobial resistance. There are few available antibiotics that are able to address these concerns. Areas covered: After a systematic review of the current literature, we describe seven novel antibiotics that are currently in advanced stages of development (phase 3 and beyond) and show promise for the treatment of CAP in those over the age of 65. These antibiotics are: Solithromycin, Pristinamycin, Nemonaxacin, Lefamulin, Omadacycline, Ceftobiprole and Delafloxacin. Using a novel conceptual framework designed by the present authors, known as the ‘San Antonio NIPS model’, we evaluate their strengths and weaknesses based on their ability to address the unique challenges that face the elderly. Expert opinion: All seven antibiotics have potential value for effective utilization in the elderly, but to varying degrees based on their NIPS model score. The goal of this model is to reorganize a clinician’s focus on antibiotic choices in the elderly and bring attention to a seldom discussed topic that may potentially become a health-care crisis in the next decade.