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.

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.

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.

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.

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.

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.

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.

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.

[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.

[Usefulness of panfungal PCR for the diagnosis of fungal infection in immunocompromised patients]. / Intérêt de l'amplification génique à l'aide d'amorces universelles dans le diagnostic des infections fongiques chez le patient immunodéprimé.

The diagnostic of invasive fungal infection is often difficult because of the low sensitivity of fungal culture from infected tissues. Here we have assessed the ability of a panfungal PCR targeted on the DNA region encoding the RNA genes followed by sequencing of the amplification products to detect and identify fungi from tissue biopsies. This assay allowed us to identify the microorganism responsible for an invasive fungal infection in three of our patients. In two cases, hepatosplenic candidiasis was suspected and Candida albicans DNA was detected from liver biopsies. The third patient was cared for a thymome and developed a manubrium osteitis caused by Scedosporium apiospermum.

Candida infections in children treated with conventional chemotherapy for solid tumors (transplant recipients excluded): The Institut Gustave Roussy Pediatrics Department experience.

INTRODUCTION: Advances in medical therapy have greatly improved the survival of children suffering from cancer. Although progress has been made in the eradication of malignant disease there is growing concern for the development of fungal infections in patients treated with chemotherapy. MATERIALS AND METHODS: We reviewed all episodes of pediatric candidemia that occurred between January 1988 and December 2000. We analyzed the general characteristics of this population, risk factors, microbiology features, treatment, complications, and outcome. RESULTS: Seventeen cases of candidemia were observed during the 12 years of the study at an estimated incidence of 0.4%. Neutropenia occurred at the onset of infection in 13/17 (76.5%) children. A central venous device was present in all cases. Seventy-seven percent of the infections were caused by Candida albicans and in 85% of patients, yeasts had colonized the gastrointestinal tract. In 9/17 patients visceral dissemination was documented. Overall, in 77% of the episodes the outcome was favorable. CONCLUSIONS: Candidemia is a rare but severe complication in pediatric oncology. Even if the prognosis is better in children than in adults, Candida septicemia remains of great concern since a high percentage of these infections result in visceral dissemination and mortality is still elevated.

[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%).

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.

[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.

Impact of quinupristin/dalfopristin (RP59500) on the faecal microflora in healthy volunteers.

The effect of 5 days' administration of quinupristin/dalfopristin (RP59500) on the faecal microflora was evaluated in healthy volunteers. Twenty healthy volunteers received 7.5 mg/kg of quinupristin/dalfopristin infused over 1 h twice daily for 5 days and four received a matched placebo. Faecal samples were collected before, during and after treatment (days -1/-2, 6, 8, 14/15, 35 +/- 2, 60 +/- 4, 90 +/- 4). In the treated volunteers, anaerobes, including sporulating and Gram-negative bacteria, decreased slightly during treatment, whereas numbers of enterococci and Enterobacteriaceae increased significantly (P < 0.01). Counts of anaerobes and enterococci resistant to erythromycin or to quinupristin/dalfopristin increased significantly (P < 0.01) during treatment and returned slowly to their baseline levels after the end of treatment. Mean faecal antibiotic concentrations reached 291 +/- 184 and 42 +/- 22 microg/g of faeces for quinupristin and dalfopristin, respectively, by the fifth day of treatment. Counts of yeasts were not influenced significantly by the treatment. No emergence of glycopeptide-resistant enterococci, Staphylococcus aureus, Pseudomonas aeruginosa or Clostridium difficile was observed. No episode of diarrhoea was reported. In conclusion, quinupristin/dalfopristin administration was associated with a temporary shift towards resistance of the endogenous flora and a temporary increase in counts of enterobacteria and enterococci. However, no decrease in colonization resistance towards exogenous potentially pathogenic bacteria was observed and the observed modifications disappeared within 12 weeks after the end of quinupristin/dalfopristin administration.

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.

Value of gram stain examination of lower respiratory tract secretions for early diagnosis of nosocomial pneumonia.

Except for bronchoalveolar lavage, the value of the Gram stain examination of respiratory tract samples for the diagnosis of hospital-acquired pneumonia (HAP) and their potential impact on empiric antibiotic treatment have rarely been assessed. During a 14-mo period, both plugged telescoping catheter (PTC) and endotracheal aspirate (EA) were performed when an HAP was suspected in mechanically ventilated patients. The results of Gram stain examinations and cultures and previous and subsequent antibiotic treatment were prospectively recorded. Two criteria for pneumonia were considered: (1) clinically diagnosed pneumonia, according to attending physicians, based on clinical and radiological evolution and the PTC culture results, and (2) microbiologically proven pneumonia (solely based on the result of quantitative PTC culture). Of 91 episodes of suspected HAP in 51 patients, 27 (30%) episodes were clinically diagnosed as pneumonia. When considering clinically diagnosed pneumonia, the sensitivity and specificity of Gram stain examination were similar (respectively, 89% and 62% for EA and 67% and 95% for PTC). When considering microbiologically proven pneumonia, the sensitivity and specificity of Gram stain examination were, respectively, 91% and 64% for EA and 70% and 96% for PTC. The negative predictive value of Gram stain examination of EA and the positive predictive value of Gram stain examination of PTC were high. Our results suggest that the combination of Gram stain examination of paired PTC and EA may contribute to the early diagnosis of HAP in about two-thirds of mechanically ventilated patients, and guide the empiric therapy when needed. In the remaining one-third of patients, the Gram stain examination is not helpful in predicting HAP.

Intranasal immunization with protein-linked phosphorylcholine protects mice against a lethal intranasal challenge with streptococcus pneumoniae.

Immunization against phosphorylcholine (PC) linked to a protein protects mice against Streptococcus pneumoniae when used parenterally, and against Salmonella typhimurium when used orally after entrapment in D,L-Lactide-co-Glycolide microspheres. Here, we immunized BALB/c mice intranasally with a serotype 3 S. pneumoniae strain. Immunization was followed by a rise in anti-PC IgA and IgG titers in serum and in pulmonary secretions, but not by any rise in anti ds-DNA antibody nor any glomerular Ig deposition. The survival rates were 91 and 76% in the two groups of mice, respectively. These rates were significantly higher than those in control mice immunized intranasally either with Thyr loaded in microspheres (0%), blank microspheres (22%), free Thyr (17%), and saline (18%). This demonstrates that the mucosal route is effective for vaccination against S. pneumoniae pneumonia with PC linked to a protein carrier. It constitutes another important step forward in the development of the concept that PC can be used as a mucosal immunogen for protection against the different diseases caused by PC-bearing bacteria.

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.