Giorgio Zanetti

Cefepime versus Imipenem-Cilastatin for Treatment of Nosocomial Pneumonia in Intensive Care Unit Patients: a Multicenter, Evaluator-Blind, Prospective, Randomized Study

ABSTRACT In a randomized, evaluator-blind, multicenter trial, we compared cefepime (2 g three times a day) with imipenem-cilastatin (500 mg four times a day) for the treatment of nosocomial pneumonia in 281 intensive care unit patients from 13 centers in six European countries. Of 209 patients eligible for per-protocol analysis of efficacy, favorable clinical responses were achieved in 76 of 108 (70%) patients treated with cefepime and 75 of 101 (74%) patients treated with imipenem-cilastatin. The 95% confidence interval (CI) for the difference between these response rates (−16 to 8%) failed to exclude the predefined lower limit for noninferiority of −15%. In addition, therapy of pneumonia caused by an organism producing an extended-spectrum β-lactamase (ESBL) failed in 4 of 13 patients in the cefepime group but in none of 10 patients in the imipenem group. However, the clinical efficacies of both treatments appeared to be similar in a secondary intent-to-treat analysis (95% CI for difference, −9 to 14%) and a multivariate analysis (95% CI for odds ratio, 0.47 to 1.75). Furthermore, the all-cause 30-day mortality rates were 28 of 108 (26%) patients in the cefepime group and 19 of 101 (19%) patients in the imipenem group (P = 0.25). Rates of documented or presumed microbiological eradication of the causative organism were similar with cefepime (61%) and imipenem-cilastatin (54%) (95% CI, −23 to 8%). Primary or secondary resistance of Pseudomonas aeruginosa was detected in 19% of the patients treated with cefepime and 44% of the patients treated with imipenem-cilastatin (P = 0.05). Adverse events were reported in 71 of 138 (51%) and 62 of 141 (44%) patients eligible for safety analysis in the cefepime and imipenem groups, respectively (P = 0.23). Although the primary end point for this study does not exclude the possibility that cefepime was inferior to imipenem, some secondary analyses showed that the two regimens had comparable clinical and microbiological efficacies. Cefepime appeared to be less active against organisms producing an ESBL, but primary and secondary resistance to imipenem was more common for P. aeruginosa. Selection of a single agent for therapy of nosocomial pneumonia should be guided by local resistance patterns.

Influence of Bacille Calmette-Guérin Vaccination on Size of Tuberculin Skin Test Reaction: To What Size?

BACKGROUND Previous bacillus Calmette-Guerin (BCG) vaccination can confound the results of a tuberculin skin test (TST). We sought to determine a cutoff diameter of TST induration beyond which the influence of BCG vaccination was negligible in evaluating potential Mycobacterium tuberculosis infection in a population of health care workers with a high vaccination rate and low incidence of tuberculosis. METHODS From 1991 through 1998, all new employees at the University Hospital of Lausanne, Switzerland, underwent a 2-step TST at entry visit. We also gathered information on demographic characteristics, along with factors commonly associated with tuberculin positivity, including previous BCG vaccination, history of latent M. tuberculosis infection, and predictors for M. tuberculosis infection. RESULTS Among the 5117 investigated subjects, we found that influence of BCG vaccination on TST results varied across categories of age (likelihood ratio test, 0.0001). Prior BCG vaccination had a strong influence on skin test results of <or=18 mm in diameter among persons <40 years old, compared with the influence of factors predictive of M. tuberculosis infection. Prior latent M. tuberculosis infection and travel or employment in a country in which tuberculosis is endemic also had significant influences. CONCLUSIONS Interpretation of TST reactions of <or=18 mm among BCG-vaccinated persons <40 years of age must be done with caution in areas with a low incidence of tuberculosis. In such a population, except for persons who have never been vaccinated, TST reactions of <or=18 mm are more likely to be the result of prior vaccination than infection and should not systematically lead to preventive treatment.

Intraoperative Redosing of Cefazolin and Risk for Surgical Site Infection in Cardiac Surgery

Intraoperative redosing of prophylactic antibiotics is recommended for prolonged surgical procedures, although its efficacy has not been assessed. We retrospectively compared the risk of surgical site infections in 1,548 patients who underwent cardiac surgery lasting >240 min after preoperative administration of cefazolin prophylaxis. The overall risk of surgical site infection was similar among patients with (43 [9.4%] of 459) and without (101 [9.3%] of 1,089) intraoperative redosing (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.70-1.47). However, redosing was beneficial in procedures lasting >400 min: infection occurred in 14 (7.7%) of 182 patients with redosing and in 32 (16.0%) of 200 patients without (adjusted OR 0.44, 95% CI 0.23-0.86). Intraoperative redosing of cefazolin was associated with a 16% reduction in the overall risk for surgical site infection after cardiac surgery, including procedures lasting <240 min.

High Proportion of Wrongly Identified Methicillin-Resistant Staphylococcus aureus Carriers by Use of a Rapid Commercial PCR Assay Due to Presence of Staphylococcal Cassette Chromosome Element Lacking the mecA Gene

ABSTRACT During a 9-month period, 217 patients were newly diagnosed as methicillin-resistant Staphylococcus aureus (MRSA) carriers by using a commercial rapid PCR-based test (GeneXpert). However, no MRSA was recovered by culturing the second swab in 61 of these patients. Further analyses showed that 28 (12.9%) of the patients harbored S. aureus isolates with a staphylococcal cassette chromosome element lacking the mecA gene and were thus incorrectly determined to be MRSA carriers.

Randomized controlled trial of peripherally inserted central catheters vs. peripheral catheters for middle duration in-hospital intravenous therapy.

Summary.  Introduction: Intravenous (i.v.) therapy may be associated with important catheter‐related morbidity and discomfort. The safety, efficacy, comfort, and cost‐effectiveness of peripherally inserted central catheters (PICCs) were compared to peripheral catheters (PCs) in a randomized controlled trial. Methods: Hospitalized patients requiring i.v. therapy ≥ five days were randomized 1:1 to PICC or PC. Outcomes were incidence of major complications, minor complications, efficacy of catheters, patient satisfaction, and cost‐effectiveness. Results: 60 patients were included. Major complications were observed in 22.6% of patients in the PICC group [six deep venous thrombosis (DVT), one insertion‐site infection] and 3.4% of patients in the PC group [one DVT; risk ratio (RR) 6.6; P = 0.03]. Superficial venous thrombosis (SVT) occurred in 29.0% of patients in the PICC group and 37.9% of patients in the PC group (RR 0.60; P = 0.20). Patients in the PICC group required 1.16 catheters on average during the study period, compared with 1.97 in the PC group (P < 0.04). The mean number of venipunctures (catheter insertion and blood sampling) was 1.36 in the PICC group vs. 8.25 in the PC group (P < 0.001). Intravenous drug administration was considered very or quite satisfying by 96.8% of the patients in the PICC group, and 79.3% in the PC group. Insertion and maintenance mean cost was 690 US

Association between a Specific Pneumocystis jiroveci Dihydropteroate Synthase Mutation and Failure of Pyrimethamine/Sulfadoxine Prophylaxis in Human Immunodeficiency Virus–Positive and –Negative Patients

for PICC and 237 US

Changing Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in a Small Geographic Area over an Eight-Year Period

for PC. Discussion: PICC is efficient and satisfying for hospitalized patients requiring i.v. therapy ≥ five days. However, the risk of DVT, mostly asymptomatic, appears higher than previously reported, and should be considered before using a PICC.

Importation of Acinetobacter baumannii Into a Burn Unit: A Recurrent Outbreak of Infection Associated With Widespread Environmental Contamination

To investigate the possible association between different prophylactic sulfa drugs and the genotype of the Pneumocystis jiroveci dihydropteroate synthase (DHPS) gene, we examined DHPS polymorphisms in clinical specimens from 158 immunosuppressed patients (38 HIV-negative and 120 HIV-positive), using polymerase chain reaction-single-strand conformation polymorphism. Fifty-seven (36.1%) of 158 patients were infected with a mutant DHPS genotype. All patients who developed P. jiroveci pneumonia (PcP) while receiving pyrimethamine/sulfadoxine (PM/SD) prophylaxis (n=14) had a strain harboring DHPS with an amino acid change at position 57 (Pro-->Ser). This mutation was only present in 20 (14%) of 144 patients not receiving prophylaxis (P<.001). Hospitalization in a specific hospital was an independent risk factor for having P. jiroveci harboring the same DHPS mutation, which indirectly supports that interhuman transmission may affect the dissemination of the mutant strains.

Improvement of intraoperative antibiotic prophylaxis in prolonged cardiac surgery by automated alerts in the operating room.

ABSTRACT The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) at an international level shows that most MRSA strains belong to a few pandemic clones. At the local level, a predominance of one or two clones was generally reported. However, the situation is evolving and new clones are emerging worldwide, some of them with specific biological characteristics, such as the presence of Panton-Valentine leucocidin (PVL). Understanding these changes at the local and international levels is of great importance. Our objective was to analyze the evolution of MRSA epidemiology at multiple sites on a local level (Western Switzerland) over a period of 8 years. Data were based on MRSA reports from seven sentinel laboratories and infection control programs covering different areas. Pulsed-field gel electrophoresis was used to type MRSA isolates. From 1997 to 2004, a total of 2,256 patients with MRSA were reported. Results showed the presence of four predominant clones (accounting for 86% of patients), which could be related to known international clones (Berlin, New York/Japan, Southern Germany, and Iberian clones). Within the small geographic region, the 8-year follow-up period in the different areas showed spacio-temporal differences in the relative proportions of the four clones. Other international MRSA clones, as well as clones showing genetic characteristics identical to those of community-acquired MRSA (SCCmec type IV and the presence of PVL genes), were also identified but presumably did not disseminate. Despite the worldwide predominance of a few MRSA clones, our data showed that at a local level, the epidemiology of MRSA might be different from one hospital to another. Moreover, MRSA clones were replaced by other emerging clones, suggesting a rapid change.

Which anatomical sites should be sampled for screening of methicillin-resistant Staphylococcus aureus carriage by culture or by rapid PCR test?

A burn patient was infected with Acinetobacter baumannii on transfer to the hospital after a terrorist attack. Two patients experienced cross-infection. Environmental swab samples were negative for A. baumannii. Six months later, the bacteria reemerged in 6 patients. Environmental swab samples obtained at this time were inoculated into a minimal mineral broth, and culture results showed widespread contamination. No case of infection occurred after closure of the unit for disinfection.