Can Pharmacokinetic and Pharmacodynamic Principles Be Applied to the Treatment of Multidrug-Resistant Acinetobacter?

OBJECTIVE: To discuss treatment options that can be used for treatment of Acinetobac/erinfections. DATA SOURCES: A MEDLINE search (1966-November 2010) was conducted to identify English-language literature on pharmacotherapy of Acinetobacter and the bibliographies of pertinent articles. Programs and abstracts from infectious diseases meetings were also searched. Search terms included Acinetobacter, multidrug resistance, pharmacokinetics, pharmacodynamics, Monte Carlo simulation, nosocomial pneumonia, carbapenems, polymyxins, sulbactam, aminoglycosides, tetracyclines, tigecycline, rifampin, and fluoroquinolones. DATA SELECTION AND DATA EXTRACTION: All articles were critically evaluated and all pertinent information was included in this review. DATA SYNTHESIS: Multidrug resistant (MDR) Acinetobacter, defined as resistance to 3 or more antimicrobial classes, has increased over the past decade. The incidence of carbapenem-resistant Acinetobacter is also increasing, leading to an increased use of dose optimization techniques and/or alternative antimicrobials, which is driven by local susceptibility patterns. However, Acinetobacter infections that are resistant to all commercially available antibiotics have been reported. General principles are available to guide dose optimization of aminoglycosides, ß-lactams, fluoroquinolones, and tigecycline for infections due to gram-negative pathogens. Unfortunately, data specific to patients with Acinetobacter infections are limited. Recent pharmacokinetic-pharmacodynamic information has shed light on colistin dosing. The dilemma with colistin is its concentration-dependent killing, which makes once-daily dosing seem like an attractive option, but its short postantibiotic effect limits a clinician's ability to extend the dosing interval. Localized delivery of antimicrobials is also an attractive option due to the ability to increase drug concentration at the infection site while minimizing systemic adverse events, but more data are needed regarding this approach. CONCLUSIONS: Increased reliance on dosage optimization, combination therapy, and localized delivery of antimicrobials are methods to pursue positive clinical outcomes in MDR Acinetobacter infections since novel antimicrobials will not be available for several years. Well-designed clinical trials with MDR Acinetobacter are needed to define the best treatment options for these patients.

Part VII. Macrolides, azalides, ketolides, lincosamides, and streptogramins.

In this article we describe antimicrobials that are grouped by their similar mechanism of action, namely inhibition of protein synthesis at the bacterial 50S ribosomal subunit. Macrolides, azalides, and ketolides are primarily used to treat community acquired respiratory tract infections. A lincosamide antibiotic, clindamycin, is primarily used to treat anaerobic infections. A combination of streptogramins, quinupristin/dalfopristin, is used to treat infections due to multiple drug resistant Gram positive cocci.

Prospective comparison of methicillin-susceptible and methicillin-resistant community-associated Staphylococcus aureus infections in hospitalized patients.

BACKGROUND: We sought to determine the proportion of community-associated Staphylococcus aureus infections due to methicillin-resistant S. aureus (CA-MRSA) at a large county hospital. In addition, we sought to identify the demographic and clinical risk factors associated with CA-MRSA infection. METHODS: Patients were prospectively enrolled if they were admitted to Parkland Hospital and had a positive culture for S. aureus isolated within 72 h of admission. The patients were interviewed using a standardized data questionnaire. Data collected included patient demographics, clinical history, as well as health care and non-health care associated MRSA risk factors. Bacterial susceptibilities were verified through review of microbiology laboratory and pharmacy records. Isolates were tested for Panton-Valentine leukocidin (PVL) gene, SCCmec type, and for inducible clindamycin resistance. RESULTS: One hundred and ninety-eight patients were interviewed prospectively, of which eight had colonization without active infection. One hundred and nineteen patients were infected with MRSA and 71 patients were infected with methicillin-susceptible S. aureus (MSSA). Patients with MRSA were more likely to be African-American and unemployed. Patients with MRSA most commonly presented with a skin or soft tissue infection (SSTI): 69% versus 45%, p=0.0012, while patients with MSSA were more likely to have infection of the respiratory tract: 11% versus 3%, p=0.02. Patients with MRSA were more likely to have used antibiotics in the past six months, been homeless, have a history of incarceration, have abused alcohol and have a history of infection with MRSA. In multivariate analysis, African-American race, antibiotics in the past six months, and a history of being homeless were associated with MRSA infection. Only 11 of 119 (9%) MRSA patients did not have at least one of these risk factors. PVL gene was present in 72 of 74 (97%) MRSA isolates and SCCmec type IV was present in 63 of 75 (84%) MRSA isolates. CONCLUSIONS: The majority of patients hospitalized with community-associated S. aureus infections were due to MRSA, most of which involved an SSTI. African-American race, recent antibiotics and past homeless status predicted infection with MRSA; however, no clinical profile could reliably exclude MRSA. Clinicians should be aware of the increasing prevalence of CA-MRSA.