Outcomes of bacteremia due to Pseudomonas aeruginosa with reduced susceptibility to piperacillin-tazobactam: implications on the appropriateness of the resistance breakpoint.

BACKGROUND: Bacteremia due to Pseudomonas aeruginosa is associated with grave clinical outcomes. Recent studies have emphasized the importance of appropriate empirical therapy, but controversy arises when piperacillin-tazobactam is used against isolates with reduced susceptibility. METHODS: We performed a retrospective cohort study of pseudomonal bacteremia from 2002 to 2006. Patients were identified by the microbiology laboratory database, and pertinent clinical data (demographic characteristics, baseline Acute Physiology and Chronic Health Evaluation [APACHE] II scores, source of bacteremia, and therapy) were retrieved from the electronic medical records. All patients received appropriate empirical therapy within 24 h of positive culture results. Patients receiving piperacillin-tazobactam were compared with those receiving other agents (control subjects). The primary outcome was 30-day mortality from the first day of bacteremia. RESULTS: A total of 34 bacteremia episodes were identified involving isolates with reduced susceptibility to piperacillin-tazobactam (minimum inhibitory concentration, 32 or 64 mg/L, reported as susceptible); piperacillin-tazobactam was empirically given in 7 episodes. There was no significant difference in baseline characteristics between the 2 groups. Thirty-day mortality was found to be 85.7% in the piperacillin-tazobactam group and 22.2% in the control group (P = .004). Time to hospital mortality was also found to be shorter in the piperacillin-tazobactam group (P < .001). In the multivariate analysis, 30-day mortality was found to be associated with empirical piperacillin-tazobactam therapy (odds ratio, 220.5; 95% confidence interval, 3.8-12707.4; P = .009), after adjustment for differences in age and APACHE II score. CONCLUSIONS: In P. aeruginosa bacteremia due to isolates with reduced piperacillin-tazobactam susceptibility, empirical piperacillin-tazobactam therapy was associated with increased mortality. Additional studies are warranted to examine the appropriateness of the current Clinical Laboratory Standards Institute resistance breakpoint of piperacillin-tazobactam.

Economic benefit of appropriate timing of vancomycin prophylaxis in patients undergoing cardiovascular surgery.

STUDY OBJECTIVE: To determine if appropriate timing of vancomycin prophylaxis in patients undergoing cardiovascular surgery results in an economic benefit by assessing the differences in total duration of hospitalization and hospital costs based on infusion start time in relation to first surgical incision. DESIGN: Prospective, observational study. SETTING: Tertiary care medical center. PATIENTS: A total of 1666 patients undergoing coronary artery bypass graft (CABG) and/or valve replacement surgery who received prophylactic vancomycin. MEASUREMENTS AND MAIN RESULTS: Appropriateness of vancomycin prophylaxis timing, based on national guidelines defining appropriate timing as start time of infusion ranging from 16-120 minutes before surgery start time, was prospectively monitored. The timing of vancomycin administration was grouped as follows: 0-15 minutes (11 patients), 16-60 minutes (156), 61-120 minutes (772), or more than 120 minutes (727) before incision. Antibiotic timing was appropriate in 928 patients and inappropriate in 738 patients. Length of hospital stay and total hospital costs were compared based on appropriateness of therapy by using multivariate linear regression and validated with a Heckman two-stage model. Median numbers of hospitalization and intensive care unit days were significantly fewer in patients given appropriate prophylaxis at an appropriate time (9 and 2 days, respectively) compared with inappropriate time (10 and 3 days, respectively, p<0.001 for both analyses). Hospital costs were significantly lower in patients who had appropriate timing of antibiotic prophylaxis (median $25,321, interquartile range [IQR] $19,429-35,471) compared with inappropriate timing (median $29,475, IQR $21,507-46,488, p<0.001). Multivariate linear regression and a Heckman two-stage model confirmed that appropriate antibiotic prophylaxis timing was associated with decreased hospitalization duration and hospital costs. CONCLUSION: In patients undergoing CABG or valve replacement surgery, the administration of vancomycin 16-120 minutes before incision significantly reduced patient hospitalization duration and total hospital costs.

An integrated pharmacoeconomic approach to antimicrobial formulary decision-making.

PURPOSE: The utility of a novel interdisciplinary approach to antimicrobial formulary decision-making was studied. METHODS: Pseudomonas aeruginosa minimum inhibitory concentration (MIC) distribution data for cefepime and ceftazidime were retrieved from nonrepeat isolates obtained from November 2002 to October 2003. Unbound drug exposures were simulated for 5000 patients using the Monte Carlo method. Weighted target attainment rates (TARs) were calculated for cefepime and ceftazidime 1 g every 8 hours and 1 g every 12 hours (infused over 0.5, 2, and 4 hours), using three representative pharmacodynamic targets (percentage of time above the MIC of 67%, 100%, and 400%). RESULTS: MIC data for 1230 nonrepeat P. aeruginosa were analyzed. The MIC at which 90% of the P. aeruginosa isolates were inhibited was 16 and 32 mg/L for cefepime and ceftazidime, respectively. Drug acquisition cost was the highest with cefepime 1 g given every 8 hours (37.56 dollars/day), followed by cefepime 1 g every 12 hours (25.04 dollars/day) and ceftazidime 1 g every 8 hours (22.26 dollars/day). When infused over 0.5 hour, the highest TAR was achieved with cefepime 1 g every 8 hours (82%), followed by ceftazidime 1 g every 8 hours (77%) and cefepime 1 g every 12 hours (66%); ceftazidime 1 g every 8 hours was 70% more cost-effective than cefepime 1 g every 8 hours. Cefepime 1 g every 12 hours, infused over 4 hours, increased the TAR to 89% and was similar in cost-effectiveness to ceftazidime 1 g every 8 hours infused over 0.5 hour. CONCLUSION: An integrated pharmacoeconomic approach to antimicrobial formulary decision-making addressed local resistance patterns, population pharmacokinetics, pharmacodynamics, dosing regimens, and drug acquisition costs. This method appeared to be more realistic and objective than the conventional approach of considering only drug acquisition costs, especially for agents in a similar structural or functional class.

The transition from open to endoscopic saphenous vein harvesting and its clinical impact: The Texas Heart Institute experience.

Open saphenous vein harvesting can be associated with wound complications, incision pain, prolonged convalescence, and poor cosmetic results. Endoscopic vein harvesting has been widely used for prevention of these problems. We compared outcomes of open and endoscopic vein harvesting for coronary artery bypass grafting at the Texas Heart Institute. We retrospectively analyzed data from 1,573 consecutive coronary artery bypass procedures performed at our institution during a 20-month period. Each procedure included saphenectomy by endoscopic vein harvesting (n = 588) performed by physician assistants, or by traditional open vein harvesting (n = 985) performed by physicians or physician assistants. The primary outcome variable was the incidence of postoperative leg infections. Both groups were similar in terms of preoperative risk factors. After surgery, leg wound infections were significantly less frequent in the endoscopic vein harvesting group (3/588, 0.5%) than in the open vein harvesting group (27/985, 2.7%; P < 0.002). The most common organism involved in leg infections was Staphylococcus (20/30, 66%): S. aureus was present in 14 of 30 infections (47%). Open vein harvesting was the only significant independent risk factor for leg infection. We conclude that endoscopic vein harvesting reduces leg wound infections, is safe and reliable, and should be the standard of care when venous conduits are required for coronary artery bypass grafting and vascular procedures. Although the transition from open to endoscopic vein harvesting can be challenging in institutions, it can be successful if operators receive adequate training in endoscopic technique and are supported by surgeons and staff.

Comparative Effects of Ceftazidime Two or Three Times Daily in Patients with Skin and Skin Structure Infections.

BACKGROUND: Skin and skin structure infections are among the most common infectious diagnoses in both the hospital and community settings. If untreated, these infections can produce serious complications. Successful antimicrobial therapy for these infections requires coverage against the causative pathogens, particularly Staphylococcus aureus. OBJECTIVE: This randomized, single-blind, multicenter study was designed to compare the efficacy and safety of intravenous ceftazidime 2 g given two times daily (BID) with that of intravenous ceftazidime 1 g given three times daily (TID) for the treatment of skin and skin structure infections caused by ceftazidime-sensitive pathogens. METHODS: Adults (greater-than-or-equal18 years) were eligible for enrollment if they were hospitalized or in home health care settings and they had a skin or skin structure infection caused by a ceftazidime-sensitive pathogen. Patients were randomly assigned to receive ceftazidime 2 g every 12 h or ceftazidime 1 g every 8 h as an intermittent infusion over 15--30 min. Treatment was continued for 2--3 days beyond the time the patient became asymptomatic or evidence of bacterial eradication was obtained; however, total treatment duration had to be at least 5 days. Patients were assessed for their clinical and bacteriological response at the end of treatment and for their clinical response at follow-up. RESULTS: A total of 806 patients were enrolled in the study, 406 of whom received ceftazidime 2 g BID and 400 of whom received ceftazidime 1 g TID. Both treatments were administered for a mean duration of 9 days. At the end of therapy, 248 of 264 (94%) clinically evaluable patients receiving ceftazidime BID and 258 of 275% (94%) clinically evaluable patients receiving ceftazidime TID achieved clinical cure or improvement (p = 0.953). Pathogens were eradicated or presumed to be eradicated from 217 of 256 (85%) bacteriologically evaluable patients receiving ceftazidime BID and from 228 of 266 (86%) bacteriologically evaluable patients receiving ceftazidime TID (p = 0.760). Of 1131 isolates, the most common pathogens were S. aureus (30%) and Pseudomonas aeruginosa (10%). Both regimens were well tolerated with only 13 patients (3%) in the BID group and 16 patients (4%) in the TID group withdrawing because of an adverse event. CONCLUSIONS: These data indicate that ceftazidime 2 g given twice daily is as effective as ceftazidime 1 g given three times daily for the treatment of skin and skin structure infections. In addition, the twice-daily regimen has the advantage of convenience.

Effectiveness of 0.12% chlorhexidine gluconate oral rinse in reducing prevalence of nosocomial pneumonia in patients undergoing heart surgery.

BACKGROUND: Decreasing the levels of bacteria in the oropharynx should reduce the prevalence of nosocomial pneumonia. OBJECTIVES: To test the effectiveness of 0.12% chlorhexidine gluconate oral rinse in decreasing microbial colonization of the respiratory tract and nosocomial pneumonia in patients undergoing open heart surgery. METHODS: A prospective, randomized, case-controlled clinical trial design was used. Peridex (0.12% chlorhexidine gluconate) was the experimental drug, and Listerine (phenolic mixture) was the control drug. A total of 561 patients undergoing aortocoronary bypass or valve surgery requiring cardiopulmonary bypass were randomized to an experimental (n = 270) or a control (n = 291) group. Nosocomial pneumonia was diagnosed by using the criteria established by the Centers for Disease Control and Prevention. RESULTS: The overall rate of nosocomial pneumonia was reduced by 52% (4/270 vs 9/291; P = .21) in the Peridex-treated patients. Among patients intubated for more than 24 hours who had cultures that showed microbial growth (all pneumonias occurred in this group), the pneumonia rate was reduced by 58% (4/19 vs 9/18; P = .06) in patients treated with Peridex. In patients at highest risk for pneumonia (intubated > 24 hours, with cultures showing the most growth), the rate was 71% lower in the Peridex group than in the Listerine group (2/10 vs 7/10; P = .02). CONCLUSIONS: Although rates of nosocomial pneumonia were lower in patients treated with Peridex than in patients treated with Listerine, the difference was significant only in those patients intubated more than 24 hours who had the highest degree of bacterial colonization.

Reducing the incidence of nosocomial pneumonia in cardiovascular surgery patients.

Outcomes management provides a mechanism to foster development of patient-driven services through revision of practice and measurement of outcomes. Because nosocomial pneumonia is the most common hospital-acquired infection in intensive care units, reducing the rate of nosocomial pneumonia became on area of intense scrutiny at our institution. This article shares an outcome initiative that focused on reducing the incidence of nosocomial pneumonia in a hospital setting. Strategies used such as multidisciplinary team formation, case/control study, quality improvement activities, risk tool development, and protocol implementation, are discussed. Process and outcome data are provided to demonstrate the initiative's positive impact. The benefits of this outcome effort are easily identified and well-illustrated. The backbone of the initiative--proactive identification of problems and the methodical, reasoned search for answers--is universally applicable.

Timing of vancomycin prophylaxis for cardiac surgery patients and the risk of surgical site infections.

BACKGROUND: Increased incidence of methicillin-resistant Staphylococcus species has required some hospitals to choose vancomycin for surgical prophylaxis. Guidelines for appropriate timing of vancomycin prophylaxis state that the infusion should begin within 120 min before the first surgical incision. However, no studies have investigated the proper timing of vancomycin prophylaxis in relationship to surgical site infections (SSI). The objective of the present study was to assess the effect of vancomycin prophylaxis timing in relation to the first surgical incision on the incidence of SSI. METHODS: We prospectively monitored vancomycin prophylaxis timing and incidence of SSI in 2048 patients undergoing coronary bypass graft or valve replacement surgery. The timing of vancomycin was categorized into five groups based on the relation between the start of the infusion and the surgical cut time. Study hypotheses were tested using logistic analysis and further validated using a Heckman two-stage model. RESULTS: The incidence of SSI were lowest in the 176 patients given vancomycin between 16 and 60 min before the surgical incision (3.4%) compared with 15 patients given vancomycin between 0 and 15 min [26.7%; relative risk (RR): 7.8; 95% CI: 2.5-24.7], 888 patients given vancomycin between 61 and 120 min (7.7%; RR: 2.2; 95% CI: 0.99-5.09), 700 patients given vancomycin between 121 and 180 min (6.9%; RR: 2.0; 95% CI: 0.87-4.62) or 269 patients given vancomycin >180 min (7.8%; RR: 2.3; 95% CI: 0.94-5.56) (P = 0.0119 by chi(2) analysis). Stepwise logistic regression analysis and a Heckman two-stage model confirmed that vancomycin administration between 16 and 60 min before the first surgical incision was associated with the lowest incidence of SSI. CONCLUSIONS: Vancomycin administration within 16-60 min before the first surgical incision reduced the risk of SSI in cardiac surgery patients.

Tolerance of vancomycin for surgical prophylaxis in patients undergoing cardiac surgery and incidence of vancomycin-resistant enterococcus colonization.

BACKGROUND: In 2001, vancomycin replaced cefuroxime for antibiotic prophylaxis in patients undergoing cardiac surgery at our institution due to high rates of surgical site infections caused by methicillin-resistant Staphylococcus spp. However, few data supported the use of vancomycin for surgical prophylaxis. OBJECTIVE: To determine the tolerance of vancomycin for antibiotic prophylaxis and incidence of vancomycin-resistant Enterococcus (VRE) in cardiac surgery patients. METHODS: In 2 separate studies, we assessed the adverse effects in patients given perioperative vancomycin (study 1) and the incidence of VRE in patients given perioperative vancomycin (study 2). Study 1 was a prospective cohort study of patients undergoing coronary artery bypass graft (CABG) or valve replacement surgery given vancomycin (1 dose preoperatively/2 doses postoperatively) for antibiotic prophylaxis between October 2003 and December 2004. Patients were assessed for tolerance to the antibiotic regimen. In study 2, cardiac surgery patients receiving perioperative vancomycin were screened for VRE before therapy and at day 7 of hospitalization. VRE was detected using standard microbiologic procedures. RESULTS: In study 1, 1161 patients (CABG = 75%; valve = 19%; both = 6%) were evaluated. All patients but one (99.9%) were prescribed preoperative vancomycin. Therapy was changed for 34 (2.9%) patients, of which 20 changes were due to physician preference for another antibiotic. The only toxicity that required a change in the vancomycin regimen was red man's syndrome, which was experienced by 9 (0.8%) patients. Four patients did not receive a second postoperative dose due to prior renal insufficiency. Patients were most commonly switched to cefuroxime (n = 26), linezolid (n = 2), cefepime (n = 2), gatifloxacin, cefazolin, levofloxacin, or ceftriaxone (n = 1, each). In study 2, 100 patients were screened for the emergence of VRE colonization. No patient was VRE positive at baseline and 4 (4%) were positive at day 7. CONCLUSIONS: Surgical antibiotic prophylaxis with vancomycin was reasonably well tolerated in CABG and valve replacement surgery, with a 4% incidence of VRE colonization.

Evaluation of antifungals in the surgical intensive care unit: a multi-institutional study.

In the USA, >50% of candidemia episodes occur in medical or surgical intensive care units (SICU). However, studies focused on patterns and rationale for antifungal use are lacking. The objective of this study was to evaluate systemic antifungal usage in SICU patients. Retrospective audit of SICU patients receiving antifungal therapy from four American hospitals. Medical records were reviewed for demographics, hospital variables, microbiology results, antifungal regimens and indications for therapy. A total of 2411 patient-days of antifungal use were evaluated in 225 patients. Fluconazole was the most frequently prescribed antifungal (1846 patient-days) followed by amphotericin B deoxycholate (251 patient-days), lipid formulations of amphotericin B (201 patient-days), itraconazole (71 patient-days), and caspofungin (42 patient-days). Antifungals were prescribed empirically (44%), for preemptive therapy in critically ill patients colonised with Candida (43%), or for candidiasis (12%). Candida species were recovered from 98% of patients with positive fungal cultures most commonly from pulmonary (53%) or urinary sources (17%). Fluconazole is the most frequently prescribed antifungal agent in SICUs and is most often prescribed for empiric or preemptive indications. Research efforts to identify patients who warrant preemptive antifungal therapy for invasive candidiasis could dramatically change antifungal prescribing patterns in the SICU.