Kathryn J. Eagye

Pharmacodynamic-based clinical pathway for empiric antibiotic choice in patients with ventilator-associated pneumonia

BACKGROUND Because of the high frequency of multidrug resistant bacteria in our intensive care units (ICUs), we implemented a ventilator-associated pneumonia (VAP) clinical pathway based on unit-specific minimum inhibitory concentration (MIC) distributions and pharmacodynamic modeling in 3 of our ICUs. METHODS This was a prospective, observational evaluation with a historical control group in adult patients (n = 168) who met clinical and radiologic criteria for VAP. Monte Carlo simulation was used to determine antibiotic regimens having the greatest likelihood of achieving bactericidal exposures against Pseudomonas aeruginosa. Antibiotic regimens were incorporated into an ICU-specific computerized clinical pathway as empiric agents of choice. RESULTS Pharmacodynamic modeling found 3-hour infusions of cefepime 2 g every 8 hours or meropenem 2 g every 8 hours plus tobramycin and vancomycin would provide the greatest probability of empirically treating VAP in these ICUs. Infection-related mortality was reduced by 69% (8.5% vs 21.6%; P = .029), infection-related length of stay was shorter (11.7 +/- 8.1 vs 26.1 +/- 18.5; P < .001), and fewer superinfections were observed in patients treated on the pathway. A number of patients with nonsusceptible P aeruginosa were successfully treated with high-dose, 3-hour infusion regimens. CONCLUSIONS In our ICUs where multidrug resistant bacteria are common, an approach considering ICU-specific antibiotic MICs coupled with pharmacodynamic dosing strategies resulted in improved outcomes and shorter duration of treatments.

Risk factors and outcomes associated with isolation of meropenem high-level-resistant Pseudomonas aeruginosa.

OBJECTIVE To determine risk factors and outcomes for patients with meropenem high-level-resistant Pseudomonas aeruginosa (MRPA) (minimum inhibitory concentration [MIC] > or = 32 microg/mL). DESIGN Case-control-control. SETTING An 867-bed urban, teaching hospital. PATIENTS Fifty-eight MRPA case patients identified from an earlier P. aeruginosa study; 125 randomly selected control patients with meropenem-susceptible P. aeruginosa (MSPA) (MIC < or = 4 microg/mL), and 57 control patients without P. aeruginosa (sampled by case date/location). METHODS Patient data, outcomes, and costs were obtained via administrative database. Cases were compared to each control group while controlling for time at risk (days between admission and culture, or entire length of stay [LOS] for patients without P. aeruginosa). RESULTS A multivariable model predicted risks for MRPA versus MSPA (odds ratio [95% confidence interval]): more admissions (in the prior 12 months) (1.41 [1.15, 1.74]), congestive heart failure (2.19 [1.03, 4.68]), and Foley catheter (2.53 [1.18, 5.45]) (adj. R(2) = 0.28). For MRPA versus no P. aeruginosa, risks were age (in 5-year increments) (1.17 [1.03, 1.33]), more prior admissions (1.40 [1.08, 1.81]), and more days in the intensive care unit (1.10 [1.03, 1.18]) (adj. R(2) = 0.32). Other invasive devices (including mechanical ventilation) and previous antibiotic use (including carbapenems) were nonsignificant. MRPA mortality (31%) did not differ from that of MSPA (15%) when adjusted for time at risk (P = .15) but did from mortality without P. aeruginosa (9%) (P = .01). Median LOS and costs were greater for MRPA patients versus MSPA patients and patients without P. aeruginosa: 30 days versus 16 and 10 (P<.01) and

Deep and organ/space infections in patients undergoing elective colorectal surgery: incidence and impact on hospital length of stay and costs.

88,425 versus

Surgical Site Infections: Does Inadequate Antibiotic Therapy Affect Patient Outcomes?

28,620 and

Length of Stay and Hospital Costs Associated with a Pharmacodynamic‐Based Clinical Pathway for Empiric Antibiotic Choice for Ventilator‐Associated Pneumonia

22,605 (P<.01). CONCLUSIONS Although antibiotic use has been shown to promote resistance, our data found that prior antibiotic use was not associated with MRPA acquisition. However, admission frequency and Foley catheters were, suggesting that infection control measures are essential to reducing MRPA transmission.

Impact of Superinfection on Hospital Length of Stay and Costs in Patients with Ventilator-Associated Pneumonia

BACKGROUND The reported incidence of infection complicating elective colorectal surgery (ECS) is 11% to 26%. We evaluated length of stay (LOS) and expense associated with such infections, which heretofore remain unexplored. METHODS We reviewed 1127 ECS procedures from October 2005 to may 2007 to identify infected case subjects (n = 46). Data were obtained by way of chart abstraction and administrative database review. A case-control study evaluated LOS and actual accounting costs for case subjects versus uninfected control subjects (n = 46). Logistic regression determined risk factors for infection. RESULTS Infection incidence was 4.1%. Mean +/- SD LOS and costs were greater for case than control subjects: 21 +/- 15 days compared with 6 +/- 4 days (P < .001) and

In vitro activity and pharmacodynamics of commonly used antibiotics against adult systemic isolates of Escherichia coli and Pseudomonas aeruginosa at Forty US Hospitals.

42,516 +/- 39,972 compared with

Pseudomonas aeruginosa is not just in the intensive care unit any more: Implications for empirical therapy

10,999 +/-

Change in antipseudomonal carbapenem susceptibility in 25 hospitals across 9 years is not associated with the use of ertapenem

7,122 (P < .001). Procedure type, infection, chronic obstructive pulmonary disease, increased age, and nonsmoking status predicted greater LOS and costs. Infection risk factors included duration of procedure > or =3 hours, male sex, higher American Society of Anesthesiologists (ASA) score, low baseline hematocrit, and indication for surgery of regional enteritis/ulcerative colitis. COMMENTS Infection development after ECS is infrequent in our population, but it results in significantly poorer outcomes. Vigilant adherence to preventive guidelines, including those for antibiotic prophylaxis, is warranted.

Empiric therapy for secondary peritonitis: A pharmacodynamic analysis of cefepime, ceftazidime, ceftriaxone, imipenem, levofloxacin, piperacillin/tazobactam, and tigecycline using Monte Carlo simulation

BACKGROUND Complicated skin/skin structure infections involve deeper soft tissues and include surgical site infections (SSIs). Inadequate antibiotic therapy (IAT) has been associated with adverse outcomes in respiratory and blood stream infections, but is seldom evaluated in SSIs. This study assessed the impact of IAT on primary outcomes of length of stay (LOS) and costs in complicated SSIs; identifying risk factors associated with receiving IAT was a secondary objective. METHODS This retrospective cohort study of discharges from our 810-bed urban teaching hospital from Quarter 4/2004-Quarter 1/2006 identified 130 patients with complicated SSI among 298 patients with postoperative infections. Superficial infections and infections not involving the skin/skin structures were excluded. Patient characteristics, culture data, and antibiotic history were collected from charts. Inadequate antibiotic therapy was said to have occurred when a drug active against the organism cultured was not given within 24 h of culture. Multiple regression identified variables associated with LOS and increase hospital accounting costs. RESULTS A total of 39 subjects (30%) received IAT; patient characteristics did not differ from those receiving adequate therapy, except that prior antibiotic use was more likely in IAT subjects (p = 0.053). Staphylococcus aureus (45% methicillin-resistant) was the most common pathogen (39%). More than one-half (60%) of the subjects received empiric vancomycin. The IAT patients experienced longer post-infection LOS and higher costs (median [25%, 75%]): 10 [6, 21] days vs. 7 [4, 11] days; p = 0.007 and