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To assess whether a potential benefit with combination antibiotic therapy is restricted to the most critically ill subset of patients, particularly those with septic shock.OVID MEDLINE (1950-October 2009), EMBASE (1980-October 2009), the Cochrane Central Register of Controlled Trials (to third quarter 2009), the ClinicalTrial.gov database, and the SCOPUS database.Randomized or observational studies of antimicrobial therapy of serious bacterial infections potentially associated with sepsis or septic shock. Fifty studies met entry criteria.Study design, mortality/clinical response, and other variables were extracted independently by two reviewers. When possible, study datasets were split into mutually exclusive groups with and without shock or critical illness.Although a pooled odds ratio indicated no overall mortality/clinical response benefit with combination therapy (odds ratio, 0.856; 95% confidence interval, 0.71-1.03; p = .0943; I = 45.1%), stratification of datasets by monotherapy mortality risk demonstrated substantial benefit in the most severely ill subset (monotherapy risk of death25%; odds ratio of death, 0.51; 95% confidence interval, 0.41-0.64; I = 8.6%). Of those datasets that could be stratified by the presence of shock/critical illness, the more severely ill group consistently demonstrated increased efficacy of a combination therapy strategy (odds ratio, 0.49; 95% confidence interval, 0.35-0.70; p.0001; I = 0%). An increased risk of death was found in low-risk patients (risk of deathor=15% in the monotherapy arm) exposed to combination therapy (odds ratio, 1.53; 95% confidence interval, 1.16-2.03; p = .003; I = 8.2%). Meta-regression indicated that efficacy of combination therapy was dependent only on the risk of death in the monotherapy group.Combination antibiotic therapy improves survival and clinical response of high-risk, life-threatening infections, particularly those associated with septic shock but may be detrimental to low-risk patients.

PURPOSE To ascertain the effect of an infection control program including process control on intensive care unit (ICU) rates of intravascular device (IVD)-associated bloodstream infection (BSI). SETTING Two level III adult ICUs in one public university hospital in Mexico: one medical surgical ICU and one neurosurgical ICU. POPULATION STUDY: All adult patients admitted to study units who had a central venous catheter (CVC) in place for at least 24 hrs. METHODS A prospective before/after trial in which rates of IVD-associated BSI are determined during a period of active surveillance without process control (phase 1) were compared with rates of IVD-associated BSI after implementing an infection control program applying process control (phase 2). RESULTS Six hundred five IVD-days were accumulated in phase 1, and 2824 IVD-days were accumulated during phase 2. Compliance with CVC site care and hand hygiene improved significantly from baseline during the study period: placing a gauze dressing over the catheter insertion site (99.24% vs. 86.69%, respectively; relative risk [RR] = 1.14; 95% confidence interval [CI] = 1.07-1.22; p = .0000), proper use of gauze for vascular catheter insertion site (97.87% vs. 84.21%, respectively; RR = 1.16; 95% CI = 1.09-1.24; p = .0000), documentation of the duration of the administration set of the vascular catheter (93.85% vs. 40.69%, respectively; RR = 2.34; 95% CI = 2.14-2.56; p = .0000), and hand hygiene before contact with the patient (84.9% vs. 62%, respectively; RR = 1.37; 95% CI = 1.21-1.51; p = .0000). Overall rates of IVD-associated BSI were lowered significantly from baseline rates after implementation of process control (19.5 vs. 46.3 BSIs per 1000 IVD-days, respectively; RR = 0.42; 95% CI = 0.27-0.66; p = .0001). Overall rates of crude unadjusted mortality were lowered significantly from baseline rates (48.5% vs. 32.8% per 100 discharges, respectively; RR = 0.68; 95% CI = 0.50-0.31; p = .01). CONCLUSION Implementation of an infection control program utilizing education, process control, and performance feedback was associated with significant reductions in rates of IVD-associated BSI and mortality.

Noncuffed, percutaneously inserted central venous catheters (CVCs) are widely used and cause at least 250,000 bloodstream infections (BSIs) in U.S. hospitals each year. We report a prospective study to determine whether inflammation at the insertion site is predictive of CVC-related BSI.Percutaneously inserted, noncuffed CVCs inserted into the subclavian, internal jugular, or femoral vein in two randomized trials during 1998-2000 were prospectively studied; most patients were in an intensive care unit. The condition of the insertion site was evaluated daily by research nurses, quantifying pain (0, 1), erythema (0-2), swelling (0, 1), and purulence (0, 1); the lowest possible overall inflammation score was 0 and the highest was 5. CVC-related BSI was confirmed in each case by demonstrating concordance between isolates from the catheter segment and from blood cultures by restriction-fragment DNA subtyping.Among 1,263 CVCs prospectively studied, 333 (26.3%) were colonized at removal; of these, 35 catheters (2.7%) caused BSIs (5.9 per 1000 CVC days). BSIs were caused by coagulase-negative staphylococci (n = 27), enterococci (n = 4), enteric Gram-negative bacilli (n = 3), or (n = 1). Most insertion sites showed little or no inflammation at the time of removal. There were no significant differences among mean scores for each inflammatory variable examined or overall score among colonized CVCs (0.1 +/- 0.1), catheters causing CVC-related BSI (0.2 +/- 0.4), and noncolonized CVCs (0.1 +/- 0.1). The sensitivity of local inflammation for diagnosis of CVC-related BSI was dismal (0-3%).Local inflammation is uncommon with infected CVCs, probably because most catheter-associated infections are currently caused by coagulase-negative staphylococci, a pathogen that incites little local or systemic inflammation. Whereas overt inflammation of the insertion site should raise suspicion of CVC-related BSI caused by or Gram-negative bacilli, especially if the patient has fever or other signs of sepsis, in general, site appearance cannot be relied on to identify catheter colonization or CVC-related BSI.

Catheter-related bloodstream infections are associated with significant costs and adverse consequences. Arterial catheters are commonly used in the critical care setting and are among the most heavily manipulated vascular access devices. We sought to evaluate the prevalence of arterial catheter-related bloodstream infection.PubMed, CinAHL, EMBASE, and Web of Science.Included studies reported prevalence rate of catheter-related bloodstream infection for arterial catheters used for critical illness or postoperative monitoring. For the purposes of this study, catheter-related bloodstream infection was defined as positive blood culture collected from an arterial catheter and from the periphery with the same organism in a patient demonstrating systemic signs of sepsis.The study population, site of insertion, antiseptic preparation, catheter days, and prevalence of catheter-related bloodstream infection were abstracted. When data were not available, authors were contacted for further information.Forty-nine studies met criteria including 222 cases of arterial catheter-related bloodstream infection in 30,841 catheters. Pooled incidence was 3.40/1,000 catheters or 0.96/1,000 catheter days. Prevalence was considerably higher in the subgroup of studies that cultured all catheters (1.26/1,000 catheter days) compared with those studies that cultured only when the arterial catheter was suspected as the source for the catheter-related bloodstream infection (0.70/1,000 catheter days). Pooled data also found a significantly increased risk of infection for femoral site of insertion compared with radial artery for arterial catheter placement (relative risk, 1.93; 95% CI, 1.32-2.84; p = 0.001) CONCLUSIONS: Arterial catheters are an underrecognized cause of catheter-related bloodstream infection. Pooled incidence when catheters were systematically cultured and correlated to blood culture results indicated a substantial burden of arterial catheter-related bloodstream infection. Selection of a radial site over a femoral site will help reduce the risk of arterial catheter-related bloodstream infection. Future studies should evaluate technologies applied to preventing central venous catheter-related bloodstream infection to arterial catheters as well.

To assess the efficacy of topical chlorhexidine for prevention of ventilator-associated pneumonia (VAP) in a meta-analysis.Computerized PubMed and MEDLINE search supplemented by manual searches for relevant articles.Randomized controlled trials evaluating efficacy of topical chlorhexidine applied to the oropharynx vs. placebo or standard care for prevention of VAP.Data were extracted on patient population, inclusion and exclusion criteria, diagnostic criteria for VAP, form and concentration of topical chlorhexidine used, incidence of VAP, and overall mortality.Data on incidence of VAP and mortality were abstracted as dichotomous variables. Pooled estimates of the relative risk and 95% confidence intervals were obtained using the DerSimonian and Laird random effects model and the Mantel-Haenszel fixed effects model. Heterogeneity was assessed using the Cochran Q statistic and I. Subgroup analyses were used to explore heterogeneity.Seven randomized controlled trials met the inclusion criteria. Topical chlorhexidine resulted in a reduced incidence of VAP (relative risk, 0.74; 95% confidence interval, 0.56-0.96; p=.02) using a fixed effects model. Using the more conservative random effects model, the point estimate was similar (relative risk, 0.70; 95% confidence interval, 0.47-1.04; p=.07), but the results failed to achieve statistical significance. The I test showed moderate heterogeneity. Subgroup analysis showed that the benefit of chlorhexidine was most marked in cardiac surgery patients (relative risk, 0.41; 95% confidence interval, 0.17-0.98; p=.04). There was no mortality benefit with chlorhexidine although the sample size was small.Our analysis showed that topical chlorhexidine is beneficial in preventing VAP; the benefit is most marked in cardiac surgery patients. A large randomized trial is needed to determine the impact of topical chlorhexidine on mortality.