Ventilator-associated pneumonia and bloodstream infections in intensive care unit cancer patients: a retrospective 12-year study on 3388 prospectively monitored patients.

PURPOSE: Some publications suggest high rates of healthcare-associated infections (HAIs) and of nosocomial pneumonia portending a poor prognosis in ICU cancer patients. A better understanding of the epidemiology of HAIs in these patients is needed. METHODS: A retrospective analysis of all the patients hospitalized for ≥ 48 h during a 12-year period in the 12-bed ICU of the Gustave Roussy hospital, monitored prospectively for ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) and for use of medical devices. RESULTS: During 3388 first stays in the ICU, 198 cases of VAP and 103 primary, 213 secondary, and 77 catheter-related BSIs were recorded. The VAP rate was 24.5/1000 ventilator days (95% confidence interval [CI] 21.2-28.0); the catheter-related BSI rate was 2.3/1000 catheter days (95% CI 1.8-2.8). The cumulative incidence during the first 25 days of exposure was 58.8% (95% CI 49.1-66.6%) for VAP, 8.9% (95% CI, 6.2-11.5%) for primary, 15.1% (95% CI 11.6-18.5%) for secondary and 5.0% (95% CI 3.2-6.8%) for catheter-related BSIs. VAP or BSIs were not associated with a higher risk of ICU mortality. CONCLUSIONS: This is the first study to report HAI rates in a large cohort of critically ill cancer patients. Although both the incidence of VAP and the rate of BSI are higher than in general ICU populations, this does not impact patient outcomes. The occurrence of device-associated infections is essentially due to severe medical conditions in patients and to the characteristics of malignancy.

Genetic context of plasmid-carried blaCMY-2-like genes in Enterobacteriaceae.

Analysis of 15 European clinical Enterobacteriaceae isolates showed that differences in the genetic context of blaCMY-2-like genes reflected the replicon type, usually IncA/C or IncI1. These blaCMY-2 loci may originate from the same ISEcp1-mediated mobilization from the Citrobacter freundii chromosome as structures described in earlier studies.

[Two cases of Bacillus infection and immunodepression]. / Infections à Bacillus et immunodépression, à propos de deux cas.

OBJECTIVE: Members of the genus Bacillus are Gram-positive bacilli, ubiquitous in the environment. When isolated in clinical practice, it is frequently considered as due to environmental contamination. Bacillus cereus is the most frequent species isolated in clinical practice, nevertheless other Bacillus spp. are sometimes isolated. Bacillus bacteremia is uncommon, the affected patients are severely ill and frequently immunocompromised with hematological malignancies. STUDY DESIGN: Two cases of bloodstream infection due to Bacillus species rarely described before are described, one due to Bacillus macerans and the other to Bacillus pumilus. Both patients presented with severe bacteremia and were immunodepressed after recent chemotherapy. They died a few days after admission to our ICU. CONCLUSION: The initial report of Bacillus spp. isolated in blood culture in oncohematological patients indicates a potentially severe infection.

Differential time to positivity of central and peripheral blood cultures is inaccurate for the diagnosis of Staphylococcus aureus long-term catheter-related sepsis.

OBJECTIVES: Differential time to positivity of cultures of blood drawn simultaneously from central venous catheter and peripheral sites is widely used to diagnose catheter-related bloodstream infections without removing the catheter. However, the accuracy of this technique for some pathogens, such as Staphylococcus aureus, is debated in routine practice. METHODS: In a 320-bed reference cancer centre, the charts of patients with at least one blood culture positive for S. aureus among paired blood cultures drawn over a six-year period were studied retrospectively. Microbiological data were extracted from the prospectively compiled database of the microbiology unit. Data concerning the 149 patients included were reviewed retrospectively by independent physicians blinded to the absolute and differential times to positivity, in order to establish or refute the diagnosis of catheter-related sepsis. Due to missing data, 48 charts were excluded, so 101 cases were actually analysed. The diagnosis was established in 62 cases, refuted in 15 cases and inconclusive in the remaining 24 cases. RESULTS: For the 64 patients with both central and peripheral positive blood cultures, the differential positivity time was significantly greater for patients with catheter-related bloodstream infections due to S. aureus (P<0.02). However, because of the high number of false-negative cases, the classic cut-off limit of 120 min showed 100% specificity but only 42% sensitivity for the diagnosis of catheter-related bloodstream infection due to S. aureus. CONCLUSIONS: These results strongly suggest that despite its high specificity, the differential time to positivity may not be reliable to rule out catheter-related bloodstream infection due to S. aureus.

Incidence and clinical significance of anaerobic bacteraemia in cancer patients: a 6-year retrospective study.

Recent studies have shown that anaerobes account for 0.5-9% of all episodes of bacteraemia in hospitalised patients, with variations according to geographical location and demographic characteristics, most notably age, but few data are available for cancer patients. This study investigated retrospectively the incidence of anaerobic bacteraemia in cancer patients who received non-surgical treatment over a 6-year period at a tertiary oncology centre. Gastrointestinal (27%) and haematological (29%) malignancies were the most common underlying diseases. Among 45 isolates of anaerobic bacteria recovered from 45 patients, Bacteroides spp. and Clostridium spp. were the most frequent pathogens (60% and 22%, respectively). Twenty episodes of bacteraemia were polymicrobial, most frequently with aerobic Gram-negative bacilli (18 cases). The mortality rate for patients with adequate antimicrobial therapy from the outset was 14%, compared with 63% for patients who were not treated adequately at any time.

Shedding of antibiotic-resistant members of the family Enterobacteriaceae in healthy residents of France and Jordan.

We compared the frequency of shedding of members of the family Enterobacteriaceae resistant to ampicillin, tetracycline, chloramphenicol, kanamycin, gentamicin and ceftazidime in 83 French residents of the Paris urban area and in 101 subjects in Jordan, 64 of whom resided in the urban area of Irbid, 15 in rural areas, and 22 of whom had a nomadic lifestyle. There was no significant difference between these populations regarding (i) the percentages of subjects with strains resistant to any of the antimicrobial agents tested and (ii) the proportions of total counts of organisms of the Enterobacteriaceae resistant to these agents. The simultaneous shedding of strains resistant to ampicillin, chloramphenicol, tetracycline and kanamycin was significantly associated with (i) exposure to antibiotic treatment during the six months preceding the study and (ii) the presence of many children at home.

Surveillance of Aspergillus galactomannan antigenemia for invasive aspergillosis by enzyme-linked immunosorbent assay in neutropenic patients treated for hematological malignancies.

INTRODUCTION: The incidence of invasive fungal infections is increasing in patients with hematological malignancies. Invasive aspergillosis is one of the most frequently encountered infections with a high mortality rate. New diagnostic tests for invasive aspergillosis such as the detection of Aspergillus galactomannan antigen by a sandwich enzyme-linked immunosorbent assay (ELISA) have recently been described. The objective of this study was to evaluate this assay as a potential surrogate for invasive procedures used to diagnose IA. MATERIALS AND METHODS: We analyzed the performance of a commercially available ELISA test which we routinely use for the surveillance of galactomannan antigenemia in patients with hematological malignancies experiencing chemotherapy-induced prolonged neutropenia (ANC < 500/mm(3) for more than 7 days). Serum samples were collected on a weekly basis. Test positivity was defined in accordance with the manufacturer's recommendations. RESULTS: Over the 2 year study period, we analyzed 507 samples obtained during 193 neutropenic episodes from 135 patients. Ten, six and two patients were considered to have proven, probable or possible invasive aspergillosis, respectively, based on clinical, radiological or microbiological data. Forty-four positive (Index>1.5) and 26 'undetermined' (1.5 > Index > 1.0) test results were observed in 17 and ten patients respectively. All invasive aspergillosis cases had at least a positive or an undetermined test result. Only one positive and one undetermined result were found in two patients before the onset of clinical or radiological signs suggesting invasive aspergillosis. Sensitivity was 69% and specificity 96% if only positive results are considered; when 'undetermined' test results were combined with positive results, sensitivity attained 100% and specificity 92% suggesting that the cutoff value for positivity can be lowered from 1.5 to 1.0. CONCLUSIONS: Although the ELISA test did not appear to play a role in the early diagnosis of invasive aspergillosis and in the anticipation of antifungal therapy in our experience, it clarifies the diagnosis of infection in probable or possible invasive aspergillosis especially when the cutoff value is lowered and is useful for monitoring patients receiving specific therapy.

Single-step polymerase chain reaction for combined gene detection and epidemiological typing in three bacterial models.

We describe a new polymerase chain reaction (PCR) for combined gene detection and epidemiological typing (COGEDET), which allows bacterial typing and gene detection in a one-step assay. This assay, in which target gene-specific primers are used under low-stringency annealing conditions, was evaluated on 32 Staphylococcus aureus strains using toxic shock syndrome toxin 1 (tst) primers, 30 Clostridium difficile strains using toxin A (toxA) primers, and 30 Escherichia coli strains using cytotoxic necrotizing factor (cnf) primers. Typing performances with COGEDET were compared to those of conventional random amplification polymorphic DNA (RAPD), and gene detection performances, to those of conventional PCR followed by Southern blot hybridization. Concordances between conventional PCR/Southern blot and COGEDET were 96.9, 100 and 96.7% for the detection of the tst, toxA and cnf genes, respectively. Discriminatory indexes for the conventional RAPD and COGEDET techniques were similar in the three bacterial species tested. These results show that the COGEDET assay can replace two separate assays for typing and genes detection respectively, thus saving both technicians' time and reagents.

Comparison of ribotyping, pulsed-field gel electrophoresis and random amplified polymorphic DNA for typing Clostridium difficile strains.

Clostridium difficile is a Gram-positive sporulating anaerobic bacillus which causes pseudomembranous colitis. Nosocomial acquisition of this bacteria has proved frequent, and epidemiological markers are needed to recognize and control common-source outbreaks. We therefore compared the results of pulsed-field gel electrophoresis (PFGE) after restriction with SmaI or NruI, random-amplified polymorphic DNA (RAPD) using 3 10-mer oligonucleotides, and ribotyping to differentiate between 30 unrelated strains of C. difficile belonging to 8 serotypes. The strains were separated into 26 different types by PFGE, 25 by RAPD, but into only 18 types by ribotyping. Median percentages of similarity between strains ranged from 27 in the PFGE assay to 90 in the ribotyping assay, but there was good agreement between the 3 methods for the clustering of strains. PFGE was more time-consuming than RAPD but its patterns were easier to analyze.

Isospora belli infection in a patient with non-Hodgkin's lymphoma.

Isospora belli infection is frequent in patients with acquired immunodeficiency syndrome in tropical areas. It has also been reported in other immunodepressive diseases, such as lymphoblastic leukemia, adult T-cell leukemia, and Hodgkin's disease. To date, no case of non-Hodgkin's lymphoma-related isosporiasis has been reported in a non-HIV-infected patient. We describe a case of non-Hodgkin's lymphoma with chronic diarrhea due to I. belli. In Europe, I. belli can cause severe chronic diarrhea in patients with malignancies whose country of origin is in an endemic area. Trimethoprim-sulfamethoxazole can provide rapid and prolonged clinical and parasitologic cure.

Decontamination of polymerase chain reaction reagents for detection of low concentrations of 16S rRNA genes.

We describe a polymerase chain reaction (PCR) that allowed detection of rRNA consensus sequences from the DNA extracted from a wide range of bacterial species in amounts as low as 10 fg. To avoid false positive results with universal primers for 16S rRNA PCR, contaminating DNA had to be eliminated from the polymerase preparations. Decontamination was undertaken before PCR to optimize treatment with DNaseI, and was followed by DNase inactivation at 94 degrees C for 50 min, which eliminated contaminating DNA at concentrations of up to 100 pg. After optimization of PCR conditions for each polymerase. Deep Vent Exo-polymerase (New England Biolabs, Beverly, MA), and super-Taq polymerase (HT Biotechnology, Cambridge, UK) were more effective than Ampli-Taq polymerase (Perkin-Elmer Cetus, Norwalk CT), Ampli-Taq LD polymerase (Perkin-Elmer Cetus) or Deep-vent polymerase (New England Biolabs). The technique described in this article might prove to be a universal method for PCR detection of small numbers of unidentified bacteria in usually sterile clinical sites, such as blood and cerebrospinal fluids, in which a broad spectrum of pathogens can be expected.

Mechanisms and risk factors for infection of pulmonary artery catheters and introducer sheaths in cancer patients admitted to an intensive care unit.

Pulmonary artery catheters (PACs) are typically inserted for short periods, and the extra-luminal route is assumed to be the overriding source of contamination and/or infection. Our aim was to assess the incidence of PAC and introducer colonization in cancer patients, and to study the mechanisms and risk factors for infection. Patients with a Swan-Ganz catheter admitted to an intensive care unit were prospectively analyzed over 14 months. As soon they were no longer necessary, PACs and introducer sheaths were removed and cultured. We recorded the mean duration of placement, the number of times PACs were handled and the site of insertion. Seventy-nine catheters were inserted in 68 patients. The median (range) duration was three days (0-10) for PACs, and 3.6 days (0-18) for introducers. PAC and/or percutaneous introducer sheath colonization was diagnosed in seven patients (8.9%), but in only one case were both colonized. Colonization rates were 15.5 per 1000 days for PACs and 14.1 per 1000 days for introducers. Introducers were mainly colonized before the 5th day, while PACs were mainly colonized after the 5th day. No PAC or introducer-related local infection or bacteraemia was diagnosed. Colonization was more frequent on catheters inserted into the internal jugular vein. The colonization rate was 5% for PACs and introducers. Our findings suggest that contamination of introducers and PACs may be dissociated and could result from either extraluminal or endoluminal colonization. As three of four PAC colonizations occurred after 5 days, the duration of catheter placement should be considered important. There was little clinical impact of microbial colonization.

[Mycologic surveillance of the environment for preventive invasive aspergillosis. Proposals for standardization of the methodologies and implementation]. / Surveillance mycologique de l'environnement pour la prévention de l'aspergillose invasive. Propositions de standardisation des méthodologies et des modalités d'application.

A MAJOR RISK: The infection of immunodepressed patients by Aspergillus-type fungi increases morbidity and mortality, particularly in hematology units or during solid organ transplantation. Although present diagnostic means benefit from the progress over the last years, they remain limited and chemoprophylaxis protocols have still not demonstrated significant efficacy. THE NEED FOR RECOMMENDATIONS: Today, the handling of environmental risks is the only strategy that has proved its efficacy and usefulness. On the basis of administrative recommendations and data from the literature, a multicentric and pluri-disciplinary task force, grouping clinicians, microbiologists and hygienists, has assessed different methods and has proposed recommendations for the standardization and optimization of fungal surveillance of the environment.

[Epidemiology and antimicrobial resistance of Streptococcus pneumoniae strains isolated in Ile de France area during 2001]. / Epidémiologie et résistance aux antibiotiques de Streptococcus pneumoniae en Ile de France en 2001.

OBJECTIVE: The authors wanted to assess the level of Streptococcus pneumoniae antibiotic resistance in Ile de France. METHOD: In 2001, 637 clinical strains of S. pneumoniae were prospectively collected from 32 microbiology laboratories. RESULTS: Fifty one percent of strains were isolated from children under 15 years of age and 49% from adults. In children, 76% of strains came from otitis media, 20% from blood culture, in adults most strains (92%) came from blood culture. The overall prevalence of non-susceptible penicillin pneumococci was 61% higher in children (73%) than in adults (50%). Among the non-susceptible penicillin pneumococci 21.8% were resistant (CMI > 1 mg/l). Strains with decreased susceptibility to amoxicillin and cefotaxime were 38% and 17% respectively. Resistant strains to these two drugs (CMI > 2 mg/l) were rare 2.6% and 0.4% respectively. Among other antimicrobial agents, rate of resistance was 63% to erythromycin, 47% to cotrimoxazole, 40% to tetracycline, and 23% to chloramphenicol. The most frequent serogroups were serogroups 19 and 14, respectively 23% and 18%. Serotypes included in heptavalent vaccine covered 90% of children strains under 2 years of age. CONCLUSIONS: The prevalence of resistance to penicillin was high in children particularly in otitis media pus (76%).

Discontinuation of empirical antibiotic therapy in neutropenic acute myeloid leukaemia patients with fever of unknown origin: is it ethical?

Based on recommendations of the ECIL-4, we prospectively evaluated discontinuation of empirical antibiotic therapy in high-risk neutropenic acute myeloid leukaemia patients with fever of unknown origin. Seven patients (median neutropenia duration 30 days) were included. Four of them remained afebrile but quickly recovered from neutropenia. The other three had rapid recurrent fever. Two of these three patients had bacteraemia with susceptible strains and one of them was transferred to the ICU for septic shock. Median duration of sparing of antibiotics for the seven patients was 3 days (2-4). Because of these limited results the study was stopped.

Factors influencing posaconazole plasmatic concentrations in patients presenting with acute myeloid leukemia.

PURPOSE: The effectiveness of posaconazole (PSZ) prophylaxis on invasive fungal infections, in patients presenting with acute myeloid leukemia (AML), seems to be correlated to its blood plasma concentration. Our goal was to identify the risk factors for underdosing. PATIENTS AND METHODS: We retrospectively reviewed the records of patients treated for AML treated with PSZ, during a 2-year period. Assays<500ng/mL were considered as under dosed. RESULTS: Fifty-nine assays (43 patients) were performed during induction (n=22) or consolidation (n=37) chemotherapy. PSZ treatment was initiated within a median of 3 days before neutropenia with a first assay performed at 8 days (3-28). The median PSZ blood plasma concentration was 375ng/mL (<200-1900). Forty-one (69%) treatment were maintained until the end of neutropenia. One patient presented with candidemia, 9 with possible invasive aspergillosis, without any significant association with underdosing. The univariate analysis showed that co-administration of proton pump inhibitors (PPIs) (P=0.01) and cause of hospitalization (induction chemotherapy vs consolidation, P=0.008) were associated with underdosing, contrary to feeding difficulties (P=0.07) and digestive disorders (P=0.5). The multivariate analysis confirmed the impact of PPI use (P=0.01) and the cause of hospitalization (P=0.003). CONCLUSION: This study highlights the major impact of PPI administration on PSZ blood plasma levels and stresses the risk of non-effective prophylaxis during induction treatment of AML.

Intravascular catheter-related bloodstream infection caused by Abiotrophia defectiva in a neutropenic child.

Bacteraemia and endocarditis are the most frequently reported clinical infections due to Abiotrophia defectiva species. This species has been rarely implicated in infections in neutropenic patients. We report a rare case of long-term venous catheter-related infection caused by A. defectiva that occurred in a febrile child who had neutropenia and Langerhans' cell histiocytosis.

Is routine changing of peripheral arterial catheters justified?

Although peripheral arterial catheters (pACs) are used extensively, disagreement persists concerning the practice of scheduled replacement to prevent catheter-related infections. Despite recommendations and no proof of benefit, pAC replacement continues to be scheduled as a routine practice in many intensive care units (ICUs) worldwide. Our own experience in an oncology ICU, based on a 217-device database, confirms that the risk for pAC-related infections is stable over time, arguing against scheduled replacement. The low rate and stability of the risk of pAC-related infections supports the rationale for conservative management in accordance with expert recommendations.

[Shelf-lives of morphine and pethidine solutions stored in patient-controlled analgesia devices: physico-chemical and microbiological stability study]. / Durée de péremption des solutions de morphine et de la péthidine présentées dans des dispositifs pour analgésie autocontrôlée: étude de stabilité physicochimique et microbiologique.

Morphine and meperidine in Patient-Controlled Analgesic devices are commonly used to treat chronic pain patients. These devices deliver a programmed amount of drug and allow self-administration by the patient depending on the pain. In our department of pharmacy, 300 devices were manufactured in 2003. The aim of this study was to assess their shelf-life. The devices were filled aseptically and without preservatives with 1 and 40 mg/ml morphine solution and 5 and 20 mg/ml meperidine and stored over 30 days at room temperature and protected from light. Culture assay of the solutions showed that they remained sterile for 30 days. No turbidity of any solutions from samples collected twice a week was noticed. pH and osmolarity remained constant. Drug concentrations were determined using stability indicating HPLC method, as we showed that degradation products can be separated from the drugs. Little loss of meperidine occurred within 21 days (<5%) and morphine concentration, which increased, because of solvent evaporation, remained lower than 5% within 21 days but increased up to 10% after 30 days. No traces of degradation products (pseudomorphine or pethidic acid) were detected. The physicochemical and microbiological stability of morphine and meperidine hydrochlorides stored in such devices has been established for 21 days at room temperature and protected from light.

Effects of roxithromycin on fecal bacteria in human volunteers and resistance to colonization in gnotobiotic mice.

The ecological impact of roxithromycin given orally at 300 mg/day on the intestinal floras in six human volunteers was studied. The resulting fecal concentrations of active roxithromycin were in the range of 100 to 200 micrograms/g of feces. Consecutive modifications in the composition of the fecal floras were limited to a decrease in counts of total members of the family Enterobacteriaceae. The rest of the intestinal floras, including the predominant anaerobic floras, changed little. No overgrowth of Pseudomonas aeruginosa, staphylococci, fungi, or highly erythromycin-resistant strains of the family Enterobacteriaceae was observed. The strains of Enterobacteriaceae and of anaerobes isolated during treatment were not markedly more resistant to roxithromycin than those isolated before treatment started. Changes in intestinal resistance to colonization by exogenous microorganisms in gnotobiotic mice inoculated with human fecal flora were studied and were also found to be minimal. The impact of oral roxithromycin on the intestinal microbiota appears to be weaker than that previously observed with oral erythromycin, perhaps because the concentrations of roxithromycin in the feces were lower than those previously found for erythromycin.