Raymond Auckenthaler

Candida colonization and subsequent infections in critically III surgical patients

ObjectiveThe authors determined the role of Candida colonization in the development of subsequent infection in critically ill patients.DesignA 6-month prospective cohort study was given to patients admitted to the surgical and neonatal intensive care units in a 1600-bed university medical center. MethodsPatients having predetermined criteria for significant Candida colonization revealed by routine microbiologic surveillance cultures at different body sites were eligible for the study. Risk factors for Candida infection were recorded. A Candida colonization index was determined daily as the ratio of the number of distinct body sites (dbs) colonized with identical strains over the total number of dbs tested; a mean of 5.3 dbs per patient was obtained. All isolates (n = 322) sequentially recovered were characterized by genotyping using contour-clamped homogeneous electrical field gel electrophoresis that allowed strain delineation among Candida species. ResultsTwenty-nine patients met the criteria for inclusion; all were at high risk for Candida infection; 11 patients (38%) developed severe infections (8 candidemia); the remaining 18 patients were heavily colonized, but never required intravenous antifungal therapy. Among the potential risk factors for candidal infection, three discriminated the colonized from the infected patients—i.e., length of previous antibiotic therapy (p < 0.02), severity of illness assessed by APACHE II score (p < 0.01), and the intensity of Candida spp colonization (p < 0.01). By logistic regression analysis, the latter two were the independent factors that predicted subsequent candidal infection. Candida colonization always preceded infection with genotypically identical Candida spp strain. The proposed colonization indexes reached threshold values a mean of 6 days before Candida infection and demonstrated high positive predictive values (66 to 100%). ConclusionsThe intensity of Candida colonization assessed by systematic screening helps predicting subsequent infections with identical strains in critically ill patients. Accurately identifying high-risk patients with Candida colonization offers opportunity for intervention strategies.

Risk Factors for Persistent Carriage of Methicillin-Resistant Staphylococcus aureus

We determined risk factors associated with persistent carriage of methicillin-resistant Staphylococcus aureus (MRSA) among 102 patients enrolled in a double-blind, placebo-controlled trial of nasally administered mupirocin ointment. MRSA decolonization was unsuccessful in 77 (79%) of 98 patients who met the criteria for evaluation. By univariate analysis, 4 variables were found to be associated with persistent MRSA colonization (P < .1 for all 4): absence of mupirocin treatment, previous fluoroquinolone therapy, > or = 2 MRSA-positive body sites, and low-level mupirocin resistance. After multivariable Cox proportional hazards modeling, the presence of > or = 2 positive body sites (adjusted hazard ratio [AHR], 1.7; 95% confidence interval [CI], 1.0-2.9) and previous receipt of a fluoroquinolone (AHR, 1.8; 95% CI, 1.0-3.3) were independently associated with MRSA persistence, whereas nasal mupirocin tended to confer protection (AHR, 0.6; 95% CI, 0.4-1.0). Low-level mupirocin resistance was observed in 9 genotypically different MRSA strains and was not independently associated with chronic MRSA carriage (AHR, 1.5; 95% CI, 0.9-2.5). Our findings suggest that multisite MRSA carriage and previous receipt of a fluoroquinolone are independent risk factors for persistent MRSA colonization.

A Comparison of Ceftriaxone and Cefuroxime for the Treatment of Bacterial Meningitis in Children

To compare ceftriaxone with cefuroxime for the treatment of meningitis, we conducted a study in which 106 children with acute bacterial meningitis were randomly assigned to receive either ceftriaxone (100 mg per kilogram of body weight per day, administered intravenously once daily; n = 53) or cefuroxime (240 mg per kilogram per day, administered intravenously in four equal doses; n = 53). The mean age of the children was 3 years (range, 42 days to 16 years), and the characteristics of the two treatment groups were comparable at admission. Excluded from the study were eight other children who died within 48 hours of admission. After 18 to 36 hours of therapy, cultures of cerebrospinal fluid remained positive for 1 of the 52 children (2 percent) receiving ceftriaxone for whom cultures were available and 6 of 52 (12 percent) receiving cefuroxime (P = 0.11). In both groups the mean duration of antibiotic therapy was 10 days. The clinical responses to therapy were similar in the two treatment groups, and all 106 children were cured. Reversible biliary pseudolithiasis was detected by serial abdominal ultrasonography only in the children treated with ceftriaxone (16 of 35 vs. 0 of 35; P less than 0.001). The treatment of three children was switched from ceftriaxone to alternative antibiotics because these children had upper abdominal pain. Other side effects were infrequent in both groups. At follow-up examination two months later, moderate-to-profound hearing loss was present in two children (4 percent) treated with ceftriaxone and in nine (17 percent) treated with cefuroxime (P = 0.05); other neurologic abnormalities were similar in the two treatment groups. We conclude that ceftriaxone is superior to cefuroxime for the treatment of acute bacterial meningitis in children and that the benefits of milder hearing impairment and more rapid sterilization of the cerebrospinal fluid with ceftriaxone outweigh the problem of reversible biliary pseudolithiasis with this drug.

Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia

Secondary pneumonia in patients requiring mechanical ventilation has a high morbidity and mortality. Diagnosis is difficult and treatment failure common; therefore, preventive measures are important. In a double-blind, placebo-controlled trial, we evaluated selective decontamination of the oropharynx with polymyxin B sulfate, neomycin sulfate, and vancomycin hydrochloride (PNV) in 52 patients requiring mechanical ventilation during a 3- to 34-day period (mean, 10 days). Either PNV or placebo was administered six times daily in the oropharynx. During the first 12 days of intubation, tracheobronchial colonization by gram-negative bacteria and Staphylococcus aureus, as well as pneumonia, occurred less frequently in the PNV than in the placebo group (16% vs 78%; P less than .0001). Hospital mortality was not different, but systemic antibiotics were prescribed less often in the PNV group and no resistant microorganism emerged. In these critically ill patients, topical oropharyngeal antibiotic application lowered the rate of ventilator-associated pneumonia by a factor of 5, probably by interrupting the stomach-to-trachea route of infection, and decreased the requirement for intravenous antibiotics.

Community-Acquired Methicillin-Resistant Staphylococcus aureus Isolated in Switzerland Contains the Panton-Valentine Leukocidin or Exfoliative Toxin Genes

ABSTRACT Among 10 strains of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolated in 2002 from patients with skin infections, seven harbored the Panton-Valentine leukocidin gene, two harbored the exfoliative toxin A gene, and one harbored neither of these genes. CA-MRSA isolates producing a variety of exotoxins are currently spreading in the Swiss community.

Influence of Previous Exposure to Antibiotic Therapy on the Susceptibility Pattern of Pseudomonas aeruginosa Bacteremic Isolates

Many patients who present with Pseudomonas aeruginosa bacteremia have been previously exposed to antibiotics. To assess whether resistance of bacteremic strains to antipseudomonal antibiotics (piperacillin, ceftazidime, imipenem, ciprofloxacin, or aminoglycosides) is associated with previous exposure to these drugs, a case-control study including 267 cases of P. aeruginosa bacteremia was conducted. Twenty-five percent of the episodes had been preceded by the exposure to an antipseudomonal antibiotic. Eighty-one strains were resistant to at least 1 antibiotic; 186 were susceptible to all drugs. Via univariate analysis, the risks of resistance to ceftazidime and imipenem were found to be significantly associated with previous receipt of these agents. Using multivariate analysis, exposure to any antipseudomonal antibiotic as a monotherapy was found to be associated with an increased risk of subsequent resistance to itself (odds ratio, 2.5; P=.006). Therefore, clinicians should avoid readministering previously prescribed antibiotics when initiating empiric therapies for possible P. aeruginosa bacteremia, especially when they have been given as monotherapies.

Treatment of experimental foreign body infection caused by methicillin-resistant Staphylococcus aureus.

A novel model of experimental foreign body infection was developed in rats: four perforated Teflon tissue cages per animal were implanted subcutaneously and 3 to 4 weeks later were infected with 0.5 x 10(5) to 2 x 10(5) CFU of methicillin-resistant Staphylococcus aureus. After 2 weeks, the number of CFU in the cage fluid was determined [day 1 mean, (7.25 +/- 0.79) log10 CFU/ml], and treatment with vancomycin (50 mg/kg twice a day [BID]), fleroxacin (50 mg/kg BID), or fifampin (25 mg/kg BID), alone and in combination, was initiated for a duration of 6 days. Concentrations of antibiotics in cage fluids were in the range of those encountered in clinical conditions. Eighteen hours after the last injection (day 7), the number of CFU in the cage fluid was determined and the difference between day 1 and day 7 values was calculated. Rifampin, alone and in combination with fleroxacin or vancomycin, was the most effective regimen in reducing the bacterial counts in the tissue cage fluids [(1.87 +/- 1.44, 2.18 +/- 1.02, and 2.55 +/- 1.09 log10) CFU/ml, P less than 0.001, respectively]. After treatment, cage fluids and cages were analyzed for resistant bacteria. Resistance to rifampin occurred in 15 of 19 cages in animals treated with rifampin alone and in 4 of 25 in animals treated with rifampin plus vancomycin. We detected no development of resistance to rifampin in animals treated with rifampin plus fleroxacin or to fleroxacin in animals treated with this antimicrobial agent. In conclusion, regimens including rifampin alone or in combination with vancomycin or fleroxacin were an effective treatment of foreign body infection due to methicillin-resistant S. aureus in reducing bacteria counts, but rifampin monotherapy was compromised by significant emergence of resistance. The combined therapy of fleroxacin with rifampin prevent development of resistance to rifampin.

Resistance occurring after fluoroquinolone therapy of experimental Pseudomonas aeruginosa peritonitis.

Resistance emerging after fluoroquinolone therapy was investigated in a murine model of Pseudomonas aeruginosa infection. Mice were infected intraperitoneally by one of six strains and treated with pefloxacin or ciprofloxacin. In mice challenged with a low inoculum (1.6 X 10(5) CFU), no resistance occurred. With a higher inoculum (1.5 X 10(8) CFU) and after a single dose of antibiotic, posttherapy (PT1) strains with decreased susceptibility to quinolones (4- to 32-fold less) were isolated at a variable rate. The presence of talcum (125 mg) in the peritoneal cavity increased the risk of resistance after therapy. Pefloxacin (25 or 200 mg/kg) and ciprofloxacin (25 mg/kg) yielded similar resistance rates (61 to 77%), but ciprofloxacin (10 mg/kg) produced more resistance (83%) than did ciprofloxacin (50 mg/kg) (44%) (P less than 0.02). Combined with a quinolone, ceftazidime (P less than 0.001) or amikacin (P less than 0.01), but not piperacillin, reduced the emergence of resistance. After several doses of ciprofloxacin, it was found that 25-mg/kg doses every 12 h produced more resistance than did 25-mg/kg doses every 8 h or 50-mg/kg doses every 12 h. Compared with the preceding experiments using parent strains, ciprofloxacin and pefloxacin were less efficient in killing bacteria in mice infected with PT1 strains. Moreover, in one of these mice, a highly resistant PT2 strain (64-fold MIC increase for the quinolones) emerged. Besides increased MICs of the quinolones, there was a two- to eightfold increase in imipenem MIC for all PT1 and PT2 strains without alteration of other beta-lactam and aminoglycoside susceptibility. Some PT1 strains also showed a decreased susceptibility to trimethoprim and chloramphenicol. During therapy with a quinolone, resistance can emerge rapidly, especially when there is a large number of bacteria or a foreign body present. This risk may depend on the dosing schedule and may be reduced by combined therapy.

Contour-clamped homogeneous electric field gel electrophoresis as a powerful epidemiologic tool in yeast infections.

To examine the longitudinal and cross-sectional patterns of yeast colonization in critically ill patients using genotypic characteristics defined by contour-clamped homogeneous electric field (CHEF) gel electrophoresis, 322 clinical isolates of Candida species were prospectively collected from 29 critically ill patients under routine surveillance over a 6-month period. All isolates, recovered from multiple anatomic sites and from the same sites on different days, were characterized by several identification methods (germ tube test), phenotyping (API system), and genotyping (electrophoretic karyotyping). Electrophoretic karyotype (EK) was determined using pulsed field electrophoresis with the CHEF technique. We used a karyotyping system for Candida albicans (EK code) that facilitated intraspecies delineation. C. albicans colonized 83% of the 29 patients. Candida sp. strains isolated from an individual patient had an identical EK pattern, even when isolated from different body sites, and remained the same over a prolonged period, up to 140 days. EK delineated not only the different Candida species, but also different strains of C. albicans. Strains of C. albicans isolated from different patients were distinguished using the EK pattern, but not API system. Minor variations in EK pattern could be demonstrated in a minority of strains recovered from four patients and were interpreted as chromosomal rearrangements between parent strains. Severe candidal infections, including eight episodes of fungemia, occurred in 11 of 29 patients (38%). All patients had been previously colonized with strains with identical EK patterns. Infection occurred a mean of 25 days after initial surveillance cultures grew yeast. No horizontal transmission could be demonstrated during the study period. In conclusion, EK is a reproducible, stable marker allowing inter-, as well as, intraspecies Candida strain delineation. EK strain delineation is a useful tool in candidal epidemiologic and pathogenic studies. Yeast colonization with the same strain preceded infection in critically ill patients.

Role of Nasopharyngeal Culture in Antibiotic Prescription for Patients with Common Cold or Acute Sinusitis

Abstract The aim of the present study was to assess the hypothesis that, when present in nasopharyngeal secretions, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis play a pathogenic role early in the course of an upper respiratory tract infection. Adults with a clinical diagnosis of acute sinusitis or common cold were enrolled. Participants were randomly assigned in a double-blind manner to receive azithromycin 500 mg daily or placebo for 3 days. The effect of treatment on symptom evolution in the predefined subset of patients with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis in their nasopharyngeal secretions was assessed. Of 265 patients enrolled, 132 received placebo and 133 azithromycin. Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis was identified in nasopharyngeal secretions of 77 patients (29%). In this predefined subgroup of patients with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, resolution of symptoms by day 7 occurred in 73% of those treated with azithromycin compared with 47% of those who received placebo (P=0.007). The median time before resolution of symptoms was 5 days in the azithromycin group compared to 7 days in the placebo group. Respiratory complications requiring antibiotic treatment occurred in 19% of patients in the placebo group and in 3% of the azithromycin group (P=0.025). In the remaining 188 patients without Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, resolution of symptoms by day 7 was similar in both groups (69% in the placebo group vs. 64% in the azithromycin group [P=0.75]). Antibiotic treatment is of clinical benefit for patients with acute sinusitis or common cold when Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis is present in nasopharyngeal secretions. This observation provides new insights into the pathogenic role of these bacteria in the early stage of the common cold.