Effect of introducing procalcitonin on antimicrobial therapy duration in patients with sepsis and/or pneumonia in the intensive care unit.

BACKGROUND: Utilizing procalcitonin (PCT) levels to limit antimicrobial overuse would be beneficial from a humanistic and economic perspective. OBJECTIVE: To assess whether introducing PCT at a teaching hospital reduced antimicrobial exposure in critically ill patients. METHODS: Patients wereadmitted to the intensive care unit (ICU) for >72 hours with sepsis and/or pneumonia. PCT levels were drawn on admission to the ICU or with new suspected infection, with at least 1 PCT level being drawn at least 48 hours later. Patients were matched in a 1:1 fashion to historical patients on age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, gender, and primary diagnosis. The primary outcome was duration of initial antimicrobial exposure defined as days from initiation of antimicrobial therapy to the intentional discontinuation of therapy by the physician. Secondary end points included length of stay, readmission to the hospital, and relapse of infection. RESULTS: There were 50 patients in the PCT group and 50 patients in the historical group. The initial duration of antimicrobials was 10 (±4.9) days compared with 13.3 (±7.2), which was statistically significant (P = .0238). The duration of stay in the hospital (13.5 compared with 17.8 days; P = .0299), readmission to the hospital (9 compared with 17; P = .055), and relapse of infection (3 compared with 11; P = .02) were seen less in the PCT group compared with controls. CONCLUSION: Introducing PCT levels resulted in a shorter duration of initial antimicrobial therapy and was not associated with adverse treatment outcomes.

Novel developments in the treatment of acute bacterial skin and skin structure infections.

Introduction: Acute bacterial skin and skin structure infection (ABSSSI) represents a major burden for healthcare systems. The increased prevalence of Methicillin-resistant Staphylococcus aureus, combined with the limited availability of microbiologic data when treating ABSSSI, has led to a need for more convenient, less toxic anti-MRSA agents. Recent approvals have added several agents to the antibiotic armamentarium that provide an expanded spectrum of activity and ease of administration compared to older agents. Areas covered: In this review, the authors discuss updated approaches to the management of ABSSSI. They also provide a review of recent FDA approved antibiotics and emerging investigational agents for treatment of ABSSSI. Expert opinion: Several new antibiotic agents have received FDA approval through the revised guidance on ABSSSI clinical trials with advantages of activity against MRSA and ease of administration. In theory, this may translate to reducing the utilization of healthcare resources by allowing for earlier discharge and reducing the need for outpatient parenteral therapy. While the approval of new agents offers the opportunity to improve and simplify treatment of ABSSSI, it is more important now than ever to use these agents in a responsible manner.

Antifungal use in immunocompetent, critically ill patients with pneumonia does not improve clinical outcomes.

PURPOSE: To determine if treating bronchoalveolar lavage (BAL) culture-positive patients with antifungal therapy impacted mortality compared to not treating due to presumed colonization. METHODS: We conducted a retrospective study of immunocompetent, critically ill adult patients from 2010 to 2014. Patients with a BAL culture-positive for Candida or unspeciated yeast and a clinical suspicion of pneumonia were included. The treatment group received an antifungal agent for at least 5 days, and the control group received either no antifungal therapy or an antifungal agent for less than 48 h. Recruitment occurred in a 2:1 ratio of untreated versus treated patients. RESULTS: Seventy-five patients were included. In-hospital mortality was similar between treated and untreated groups (24% vs. 26%, P = 0.85). Length of stay and duration of mechanical ventilation also did not differ between the two groups. CONCLUSION: We did not observe a difference in mortality or clinical outcomes in patients treated with antifungal agents. Presumptive antifungal therapy for BAL-positive Candida or yeast in immunocompetent patients did not result in improved clinical outcomes.

Nonantimicrobial effects of antibacterial agents.

One of the major advances in modern medicine was the development of antimicrobial chemotherapy. However, many antibacterial agents have unexpected or undesirable nonantimicrobial effects on humans. Microbes and man share many essentials of life, including DNA, adenosine triphosphate, and other biochemical pathways. Hence, some of these nonantimicrobial effects may also turn out to be pharmacologically useful. Oral hypoglycemic agents (i.e., sulfonylureas) and a certain diuretic agent (acetazolamide) are derivatives of sulfonamides. Erythromycin has been used clinically for its stimulatory effect on gastrointestinal motility. Macrolides, lincosamides, and tetracyclines have been known for their immunomodulatory effects. A tetracycline has been used to treat the syndrome of inappropriate antidiuretic hormone. Aminoglycosides may influence mucus production in patients with cystic fibrosis. Other antimicrobials may have side effects that are not therapeutically useful, such as osmotic diuresis with high-dose beta -lactam administration, neuromuscular blockade of aminoglycosides, dysglycemia of fluoroquinolones, and serotonin syndrome with oxazolidinones.

Methicillin-resistant Staphylococcus aureus nosocomial pneumonia patients treated with ceftaroline: retrospective case series of 10 patients.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a common nosocomial pneumonia (NP) pathogen in US ICUs. Ceftaroline fosamil is a novel cephalosporin with activity against MRSA. METHODS: We retrospectively reviewed patients (pts) who received ceftaroline therapy for MRSA NP. RESULTS: A total of 10 pts received ceftaroline from September 2011 to September 2012 for MRSA NP. Nine pts received prior anti-MRSA therapy before initiation of ceftaroline. Ceftaroline duration of therapy ranged from 4 to 28 days. Three pts pursued palliative care prior to completion of therapy and expired off antibiotics. Of the remaining seven pts, six pts were considered to have clinical cure or improvement either at the end of therapy with ceftaroline or total antibiotic treatment. One pt had a relapse 1 week after ceftaroline treatment. CONCLUSIONS: This case series suggests the potential of ceftaroline as an alternative agent for the treatment of MRSA NP and warrants further investigation.

Impact of an antimicrobial stewardship program on patients with acute bacterial skin and skin structure infections.

PURPOSE: The impact of an antimicrobial stewardship program (ASP) on the management of therapy and hospital resources for patients with acute bacterial skin and skin structure infections (ABSSSIs) at a community teaching hospital was evaluated. METHODS: A retrospective, observational chart review was performed to evaluate the impact of the ASP on patients admitted to Akron City Hospital with a diagnosis of ABSSSI between February 1 and August 20, 2012. Information on patient demographic characteristics, comorbidities, ABSSSI subtype, antibiotic therapy, microbiology, surgical interventions, and ASP recommendations was collected from medical records and the ASP intervention log. ASP recommendations were organized into five categories: dosage changes, de-escalation, antibiotic regimen change (i.e., change antibiotic regimen to a broad-spectrum antimicrobial or target a pathogen not being covered), infectious diseases (ID) formal consultation, and other. RESULTS: A total of 62 patients were included in the study. A total of 85 recommendations were made to attending physicians for these 62 patients, with an acceptance rate of 95%. The most common interventions included dosage changes, de-escalation, antibiotic regimen change, and ID consultation. When compared with historical data for 1149 patients, the intervention group had a significantly lower mean length of stay (LOS). The 30-day all-cause readmission rate was also significantly lower in the intervention group; however, the 30-day ABSSSI readmission rate did not differ significantly between groups. CONCLUSION: Interventions made by an ASP including a clinical pharmacist were associated with significant reductions in the mean LOS and 30-day all-cause readmission rate for patients with an ABSSSI compared with historical data.

Evaluation and use of a rapid Staphylococcus aureus assay by an antimicrobial stewardship program.

PURPOSE: The performance of a rapid test for methicillin-resistant Staphylococcus aureus (MRSA) in a large community hospital was investigated. METHODS: A prospective observational study was conducted to evaluate an immunochromatographic assay (Alere PBP2a Culture Colony Test, Alere Scarborough, Inc.) for rapid differentiation of MRSA and methicillin-susceptible S. aureus (MSSA) strains using isolates cultured overnight on common laboratory media. S. aureus isolates cultured for 12-24 hours were tested with the assay, which detects penicillin-binding protein 2a (PBP2a) and provides results in six minutes. The test results were compared with data from standard overnight antimicrobial susceptibility testing to determine the assay's sensitivity and specificity. Changes in therapy associated with use of the rapid assay were evaluated. RESULTS: Over an 11-month period, 661 inpatient isolates from mostly nonhematologic sites were tested. There were six false-negative results, indicating assay sensitivity of 98.4%, with no false positives (specificity of 100%). Eight invalid test results were documented. During designated evaluation periods, a total of 169 patient cases involving PBP2a testing were reviewed by the hospital's antimicrobial stewardship pharmacist. In 63 of those cases (37%), changes in therapy were implemented on the day of test result posting. Interventions often involved switching patients from inappropriate to appropriate MRSA therapy or optimizing MRSA- or MSSA-targeted therapy. CONCLUSION: An assay for quickly differentiating between MRSA and MSSA was highly sensitive, highly specific, and inexpensive in actual hospital use and led to rapid prescription of appropriate antistaphylococcal therapy 24-48 hours after culture specimens were collected.

Emergence of methicillin-resistant Staphylococcus aureus USA300 genotype as a major cause of late-onset nosocomial pneumonia in intensive care patients in the USA.

OBJECTIVE: To compare demographic and clinical characteristics, and methicillin-resistant Staphylococcus aureus (MRSA) strain characteristics, in patients with early-onset (EO) and late-onset (LO) MRSA nosocomial pneumonia. METHODS: This was a retrospective analysis of data from a multicenter observational study of nosocomial pneumonia patients admitted between November 2008 and July 2010. Laboratory analyses performed on MRSA isolates included confirmation of antimicrobial susceptibility and heteroresistance to vancomycin, USA typing, staphylococcal cassette chromosome (SCC) mec typing, and detection of Panton-Valentine leukocidin (PVL) genes. RESULTS: We identified 134 patients; 42 (31%) had EO MRSA pneumonia and 92 (69%) had LO MRSA pneumonia. The patients in the LO group were more likely to have risk factors for multidrug-resistant pathogens (98% vs. 76%, p<0.001). The MRSA USA300 strain was found with equal frequency in the EO and LO groups. Likewise, both groups had similar frequencies of isolates exhibiting PVL and SCCmec type IV. CONCLUSIONS: Our findings provide further evidence of the continued migration of community-associated MRSA into the healthcare setting in the USA. MRSA USA300 genotype has emerged as a significant cause of LO nosocomial pneumonia in intensive care units. Appropriate anti-MRSA antimicrobial therapy should be considered for both EO and LO hospital-acquired pneumonia and ventilator-associated pneumonia.

Maraviroc: a coreceptor CCR5 antagonist for management of HIV infection.

PURPOSE: The mechanism of action, pharmacology, pharmacokinetics, clinical efficacy, drug interactions, adverse effects, dosage and administration, cost, and role in therapy of maraviroc are reviewed. SUMMARY: Maraviroc is the first CCR5 coreceptor antagonist to receive marketing approval from the Food and Drug Administration (FDA) for the treatment of CCR5-tropic human immunodeficiency virus (HIV) infection as part of an optimized antiretroviral regimen in treatment-experienced patients. As 50% or more of treatment-experienced patients may be infected with CXCR4-tropic virus, a tropism assay should be performed before initiating maraviroc therapy. The majority of evidence supporting maraviroc's use comes from two studies of HIV-infected, treatment-experienced patients. Pooled analysis from these two studies revealed that twice-daily maraviroc decreased HIV-1 RNA by 1.84 log copies/mL, compared with 0.78 log copy/mL with placebo. Forty-six percent of subjects attained an HIV-1 RNA concentration of <50 copies/mL, compared with only 17% with placebo. In a trial of treatment-naive HIV-infected individuals, maraviroc failed to show noninferiority to efavirenz. Maraviroc is metabolized by cytochrome P-450 isoenzyme 3A4 and is subject to interactions with inhibitors and inducers of that isoenzyme, such as the protease inhibitors (except tipranavir), efavirenz, and rifampin. Resistance has been reported with maraviroc, but specific mechanisms are still poorly understood. The most common adverse effects reported with maraviroc were diarrhea, nausea, fatigue, and headache. CONCLUSION: Available data support the use of maraviroc, the first CCR5 antagonist to receive FDA marketing approval, as part of an optimized antiretroviral regimen in treatment-experienced patients infected with CCR5-tropic HIV.

Update on antimicrobial agents: new indications of older agents.

The discovery of newly recognised pathogens and the emergence of antimicrobial resistance have led to the development of new antimicrobial agents or to new indications for older agents. The indications have continued to increase because of new discoveries on the older agents' antimicrobial and non-antimicrobial activities. Macrolides and tetracyclines have received attention for their non-antimicrobial properties and potential use in chronic inflammatory disorders. Doxycycline, minocycline and trimethoprim-sulfamethoxazole regained interest for their activity against methicillin-resistant Staphylococcus aureus, whereas colistin has regained interest for its activity against multiple drug-resistant, Gram-negative pathogens (i.e., Pseudomonas aeruginosa). Despite the recent development of new antimicrobial agents, older and less costly agents maintain an important role today in the treatment of infectious diseases.