Christy A. Varughese

High incidence of neutropenia in patients with prolonged ceftaroline exposure

OBJECTIVES We sought to determine the rate of incident neutropenia and identify potential clinical factors associated with incident neutropenia among patients treated with long courses of ceftaroline. METHODS We retrospectively identified adult patients who received ceftaroline for ≥7 days consecutively at two large academic medical centres in Boston, USA between November 2010 and March 2015. Clinical characteristics (age, gender, medication allergies, baseline renal function, duration of ceftaroline exposure, total daily ceftaroline dose, body mass-adjusted ceftaroline dose and development of rash and neutropenia) were recorded and the rate of incident neutropenia was calculated. The Naranjo probability scale was used to assess whether ceftaroline exposure was associated with neutropenia. We assessed whether clinical factors were associated with neutropenia. RESULTS The overall rate of incident neutropenia was 10%-14% with ≥2 weeks and 21% with ≥3 weeks of ceftaroline exposure. The median duration of ceftaroline exposure [26 days (IQR 22-44; range 13-68) in patients who developed neutropenia and 15 days (IQR 9-29; range 7-64) in patients without neutropenia] was associated with incident neutropenia (P = 0.048). The median total number of ceftaroline doses received [63 (IQR 44-126; range 36-198) by neutropenic patients and 32 (IQR 22-63; range 14-180) by non-neutropenic patients] was also associated with incident neutropenia (P = 0.023). CONCLUSIONS The overall rate of neutropenia was high and associated with duration of ceftaroline exposure and total number of doses received. Close laboratory monitoring is warranted with long-term ceftaroline use.

Antibiotic-associated diarrhea: a refresher on causes and possible prevention with probiotics--continuing education article.

Antibiotic-associated diarrhea (AAD) describes any unexplained diarrhea associated with the use of an antibiotic. AAD also includes infection caused by Clostridium difficile, however this organism only accounts for a small percentage of diarrhea caused by antibiotics. AAD can be caused by multiple other organisms including C perfringens, S aureus, and Candida. Some antibiotics are more likely to cause non–C difficile AAD, such as erythromycin and the penicillin class. AAD develops through the loss of normal flora and reduced colonic bacterial carbohydrate metabolism during antibiotic administration. There is an increasing interest in the use of probiotics for the prevention of AAD. There are several meta-analyses that report a relative risk reduction of AAD with the use of probiotics during antibiotic administration. Interpretation of these studies has been challenging due to the heterogeneity and size of the patient populations, unclear probiotic regimen, and unclear safety profile. Since AAD can be a reason for a patient to become non-compliant or receive incomplete treatment, clinicians should monitor for this potential adverse effect caused by antibiotics.

Antimicrobial stewardship programs (ASPs): the devil is in the details.

Infectious disease clinicians traditionally have had the leadership role in recommending appropriate and optimal antibiotic use of antibiotics in hospitals. This judicious and optimized use of antimicrobial agents is the central principle of antimicrobial stewardship. In addition to increased awareness among infectious disease experts, antimicrobial stewardship has become a national priority. Recently, the US Food and Drug Administration (FDA) promoted antimicrobial stewardship by creating incentives to encourage new anti-infective research. The Infectious Diseases of Society of America (IDSA) launched the campaign “Bad Bugs, No Drugs” to plead for the development of new systemic antibiotics.1 While efforts at stewardship are important in their own right, the relative paucity of new agents and the spread of multi-drug resistant organisms have further emphasized the need for antimicrobial stewardship programs (ASPs) in order to preserve the antimicrobial agents that are currently available.

Tracking Colistin-Treated Patients to Monitor the Incidence and Outcome of Carbapenem-Resistant Gram-Negative Infections

BACKGROUND Existing surveillance mechanisms may underestimate the incidence of carbapenem-resistant gram-negative infections (CRGNIs). Although carbapenem resistance increases the risk of death, the trend in mortality over time is unknown. METHODS A retrospective cohort study was conducted at 40 academic medical centers using a discharge database to identify adult hospital admissions without cystic fibrosis in 2006-2012 and received intravenous colistin for >3 consecutive days or died during therapy (termed colistin cases). The primary outcomes were the number of colistin cases per 100,000 admissions per year and change in the hospital mortality rate over time compared with the rate of discharges to home. Secondary outcomes included median overall and intensive care unit lengths of stay. RESULTS From 2006 to 2012, a total of 5011 unique patients were identified as colistin cases. The number per 100,000 admissions per year increased from 35.56 to 92.98 during the 7-year study (P < .001). The odds of in-hospital death among colistin cases (compared with discharge to home) decreased by a mean of 5.2%/y (P = .04), whereas discharge to an institution (P = .24) or hospice (P = .89) remained steady over time. The median overall and intensive care unit lengths of stay decreased by 7.5 and 6 days, respectively (P < .001). In a 4-hospital chart review, 81.6% of colistin cases were found to have culture-positive CRGNIs. Conversely, 53% of extensively drug-resistant bloodstream CRGNIs at 2 of these hospitals met colistin case criteria. CONCLUSIONS Colistin cases represent a severely ill population with a high probability of having culture-confirmed CRGNIs. Colistin tracking is a novel strategy for monitoring the incidence and mortality of CRGNIs, particularly those caused by extensively drug-resistant bacteria. Although the incidence of colistin cases nearly tripled within 7 years, more of these patients are surviving hospitalization and going home.

Ceftaroline Desensitization Procedure in a Pregnant Patient With Multiple Drug Allergies

Validated skin testing is lacking for many drugs, including ceftaroline. The cross-reactivity between ceftaroline and other β-lactam antibiotics is unknown. We report a case of a pregnant patient with cystic fibrosis and multiple drug allergies who required ceftaroline for methicillin-resistant Staphylococcus aureus pneumonia and underwent an uncomplicated empiric desensitization procedure.

Preceptor development: Responses to frequently asked questions from preceptors in academic hospitals.

Preceptor development continues to be a trending topic within our profession. ASHP’s accreditation standards include requirements for preceptor development, and residency program directors continue to seek novel and unique methods for developing preceptors’ aptitude and ability for teaching.[1][

A Case of Linezolid Induced Toxicity

Adverse effects of linezolid are typically limited to diarrhea, nausea, and headache when shorter durations are used; however, as extended durations of linezolid therapy are increasingly more common, additional monitoring parameters should be considered in these patients. We describe a unique case of hypoglycemia, lactic acidosis, and pancreatitis related to an extended duration of linezolid therapy. A 52-year-old woman presented with altered mental status, abdominal pain, and hypotension following six weeks of linezolid and ertapenem therapy. Laboratory data revealed an initial blood glucose of 40 mg/dL and metabolic acidosis secondary to lactic acidosis. Finally, her abdominal pain on admission was likely related to an enlarged pancreas noted on computed tomography of her abdomen. Due to suspected linezolid toxicity, the patient received two intermittent hemodialysis sessions to remove linezolid and correct the metabolic acidosis. Given limited data on long-term monitoring of patients receiving extended durations of linezolid therapy, we suggest periodic monitoring of lactate, arterial blood gas, and blood glucose. If patients present with this triad of symptoms secondary to linezolid therapy, adverse effects should be treated with dextrose and intravenous thiamine while reserving hemodialysis for those with metabolic acidosis refractory to thiamine.