Journal of Pharmacy Practice

Over the last decade there has been a decreased number of novel antimicrobial agents introduced to the market due to multiple factors including reduced governmental funding, marginal research and development interest by the pharmaceutical industry, lack of return on investment relative to medications used for chronic illnesses, and spiking microbial resistance trends. In an effort to most judiciously use the available armamentarium of anti-infectives available, many hospitals are implementing stewardship programs to re-direct inappropriate antibiotic use, which is estimated to account for up to 50% of all antibiotics prescribed. These efforts make it increasingly evident that the best defense against inappropriate antimicrobial use is accurate diagnosis of infectious diseases. Both the public and federal government must recognize the need for new and improved antimicrobials, as well as augmented infection control strategies and diagnostic techniques, to appropriately aid in the facilitation of bacterial control or eradication.

An accurate, appropriately collated antibiogram represents an integral resource for health care providers when assessing bacterial resistance and guiding antimicrobial selection and formulary decisions. Interpretation of bacterial susceptibility statistics is problematic yet frequent and unrecognized pitfalls may be avoided by following the M39-A2 guidelines to ensure correct analysis and presentation of cumulative antimicrobial susceptibility test data. This review addresses guideline recommendations related to antibiogram development, CLSI breakpoint interpretation, antimicrobial inclusion decisions, and the avoidance of duplicate and surveillance isolates. Unit-specific antibiograms in critical care units is encouraged for differentiation between hospital-wide ecology and these specific areas harboring more resistant pathogens. Antibiograms cannot track the emergence of microbial resistance during therapy and discrepancies exist between automated microbiology surveillance systems and their agreement with manual surveillance methods. When striving to improve overall patient outcomes, the use of a well-produced and disseminated antibiogram helps guide clinical decision making for patients requiring antimicrobial therapy.

Infections caused by methicillin-resistant Staphylococcus aureus have been documented since the 1960s. Four decades later, this microorganism has evolved from a pathogen found primarily in the health care environment to a major pathogen of community-acquired infections. Interestingly, the community-acquired methicillin-resistant Staphylococcus aureus isolates tend to be genetically distinct from their health-care–acquired relatives, have a propensity to be more virulent, yet be susceptible to more antibiotics. Furthermore, infections caused in the pediatric population have a susceptibility pattern that differs from those found in adults. With an increase in infections caused by methicillin-resistant Staphylococcus aureus, empiric therapy should contain an agent with activity against this microorganism. Currently several options exist for the treatment of skin and skin structure infections, yet very few options are available for the treatment of more invasive diseases caused by methicillin-resistant Staphylococcus aureus. This article will review the history of methicillin-resistant Staphylococcus aureus, Staphylococcus aureus economic considerations, and the current plus future treatment options for these infections.

Beta-lactamase enzymes produced by gram-negative bacilli were identified before the first beta-lactam antibiotics were used to treat infections. As these enzymes adapted to available beta-lactam agents, newer beta-lactam agents were developed. Development and widespread use of the oxyimino-cephalosporins led to the emergence of extended-spectrum beta-lactamase enzymes that hydrolyze the penicillins, extended-spectrum cephalosporins, and aztreonam. There are now over 200 recognized ESBLs in a variety of gram-negative bacilli conferring resistance to penicillins, cephalosporins, a monobactam, and even carbapenems. The emergence of these enzymes is associated with poor patient outcomes, increased total health care costs, and more carbapenem use. Carbapenems should be selected judiciously to optimize outcomes while preventing further selection of extended-spectrum beta-lactamase resistance.

Fluoroquinolone antibiotics have been used for more than 40 years to treat a variety of infections from simple uncomplicated urinary tract infections to infections as severe as nosocomial-acquired pneumonia. Their availability both orally and intravenously, ease of dosing, favorable safety profile, and broad spectrum of activity have led to the pervasive use of these agents in both the community and institutions. Unfortunately, this widespread use has led to the development of resistance and subsequently, increased mortality. Resistance, specifically with Pseudomonas aeruginosa and Escherichia coli, as well as their association with the development of Clostridium difficile–associated diarrhea, has led many clinicians to question the use of fluoroquinolones in the critically ill. This article will review these issues related to the use of fluoroquinolones, in an effort to better define their role among institutionalized patients.

The incidence of invasive pneumococcal disease in children has drastically decreased since the introduction of the 7-valent pneumococcal conjugate vaccine in the United States in 2000. However, epidemiology studies are now finding that non-vaccine serotypes are emerging and are associated with multidrug resistance. Specifically, the incidence of the non-vaccine serotype 19A causing invasive pneumococcal disease has increased over the past few years. Several studies from various areas of the United States report changes in serotypes and antimicrobial resistance associated with Streptococcus pneumoniae causing invasive disease, such as meningitis, bacteremia, and pneumonia. Evidence regarding the 19A isolate emergence in otitis media and mastoiditis is now being identified and detailed. Practitioners must be aware of this evolving pneumococcal organism and the potential clinical impact in children.

Streptococcus pneumoniae represents an important pathogen in numerous community-acquired respiratory infections. Penicillin resistance to Streptococcus pneumoniae in the United States has approached 35%. Additionally, there has been a significant increase in Streptococcus pneumoniae resistance among many other antimicrobial agents such as cephalosporins, macrolides, trimethoprim–sulfamethoxazole, clindamycin, tetracyclines, and chloramphenicol. Several nationwide surveillance programs have been implemented to quantify the prevalence of Streptococcus pneumoniae resistance in the United States. Overall, beta-lactam, macrolide, trimethoprim–sulfamethoxazole, and tetracycline resistance has increased over the past decade while later generation fluoroquinolones (levofloxacin and moxifloxacin) resistance has remained low. Controlling the spread of resistant pneumococcal isolates and preventing the development of both fluoroquinolone and multidrug resistant isolates will require a multidisciplinary approach involving physicians, pharmacists, microbiologists, and epidemiologists.

Sepsis, severe sepsis, and septic shock are common diagnoses in intensive care units worldwide. In the United States, it is estimated that 750 000 cases of sepsis occur annually. This rate is expected to climb, with an additional 1 million cases per year expected by 2020. These infection-induced inflammatory syndromes ultimately lead to organ dysfunction, and a significantly high mortality rate. Recently, advances in knowledge of sepsis syndrome have led to progress in identifying potential treatment options beyond our current standards of care. Many health care facilities have implemented protocols to guide clinicians to use such standards: early goal-directed therapy and activated protein C therapy in qualifying patients. Nonetheless, debate continues to confuse identification of patient populations in whom corticosteroid therapy should be recommended. While the data describing studies of novel treatment approaches has been controversial in some cases, there have been promising results observed in others. Here we review several treatments that have recently gained attention in the medical literature: HMG-CoA reductase inhibitors (statins), selenium therapy, immunoglobulin therapy, and several agents currently in preclinical study.

Nosocomial pneumonia is the second most common hospital-acquired infection, after urinary tract infection; however, it carries with it a mortality rate estimated to be between 20% and 50%. Furthermore, patients with nosocomial pneumonia are hospitalized for an additional 7 to 9 days with an attributable cost of $40 000 or more per patient compared to patients without nosocomial pneumonia. While treatment options vary, initial empiric treatment of nosocomial pneumonia should include antimicrobials that will have activity against the organisms that will likely be encountered, including, but not limited to, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter species, Klebsiella pneumoniae, Enterobacter subspecies, Serratia marcescens, and Stenotrophomonas maltophilia. During a time of increasing resistance, it is crucial that early recognition along with appropriate treatment and dosing strategies are employed to achieve successful outcomes. The goal of this article is to update clinicians about nosocomial pneumonia and provide information regarding caveats to selecting and dosing antimicrobials, so informed decisions can be made when treating this serious condition.