Less frequent catheter dressing changes decrease local cutaneous toxicity of high-dose chemotherapy in children, without increasing the rate of catheter-related infections: results of a randomised trial.

Cutaneous lesions caused by catheter dressing changes can be serious and generate local pain in children undergoing high-dose chemotherapy followed by bone marrow transplantation. One hundred and thirteen children entered a randomised trial to compare two catheter dressing change frequencies (15 days vs 4 days). Skin toxicity was classified according to the following scale: grade 0: healthy skin, to grade 4: severe skin toxicity. A qualitative culture of the skin at the catheter entry site was taken whenever the dressing was changed. Of the 112 evaluable children (56 in each group) 32 developed grade > or = 2 local skin toxicity (eight in the 15-day group and 24 in the 4-day group; P = 0.001). Although higher in the 4-day group, the proportions of children experiencing pain during and between dressing changes were not statistically different between the two groups. The proportion of patients with one or more positive skin culture(s) at the catheter entry site during hospitalisation were similar in the two groups (27% in the 15-day group and 23% in the 4-day group) as were the proportions of documented nosocomial bloodstream infections (11% and 13%; NS). Whereas the planned frequency was maintained in the 4-day group (mean = 4 days, s.d. = 1), it was usually shortened in the 15-day group (mean = 8 days, s.d. = 4), mainly because dressings had loosened. Decreasing the catheter dressing change frequency proved efficient in reducing cutaneous toxicity without increasing the risk of local and systemic infection. In our unit, catheter dressings are changed every 8 days since this analysis.

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.

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.

Diagnosis of catheter-related bacteraemia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures.

BACKGROUND: A method of diagnosing catheter-related infection (CRI) without removing the catheter would be useful. An earlier positivity of central compared with peripheral venous-blood cultures may be associated with catheter-related bacteraemia. We evaluated prospectively the differential time to positivity (DTP) of paired blood cultures drawn simultaneously via the catheter hub and from a peripheral venous site. METHODS: Over a 14-month period in an intensive-care unit of a cancer referral centre, simultaneous hub-blood and peripheral-blood cultures (a mean of two per patient) were obtained from patients with a suspected CRI. According to clinical criteria and quantitative culture of the catheter tip, cases were classified as CRI or sepsis of other origin. At least one pair of hub-blood and peripheral-blood cultures was obtained within 48 h before catheter removal, and we recorded the DTP between hub-blood and peripheral-blood cultures with an automatic device for detection of blood culture positivity. FINDINGS: We analysed 93 catheters removed because of suspicion of CRI. In 28 episodes, the same micro-organisms were found in both hub-blood and peripheral-blood cultures. A diagnosis of definite bacteraemic CRI was made in 16 of the 17 patients in whom a positive hub-blood culture was detected at least 2 hours earlier than peripheral-blood culture. About half (9/17) of these episodes occurred in long-term (>30 days) devices. CRI was excluded in ten of the 11 patients with a DTP lower than 2 h. The DTP of paired blood cultures was significantly greater in patients with CRI than in others (p<10(-4)). A cut-off DTP value of 120 min had 91% specificity and 94% sensitivity for the diagnosis of CRI. Three of 17 episodes with only hub-blood culture positive were associated with CRI. INTERPRETATION: This prospective study suggests that measurement of the differential time to positivity between hub-blood and peripheral-blood cultures is a simple and reliable tool for in-situ diagnosis of catheter-related sepsis in cancer patients. Further studies are needed to confirm these data for short-term catheters.

[Infection prophylaxis in open leg fractures. Comparison of a dose of pefloxacin and 5 days of cefazolin-oxacillin. A randomized study of 616 cases]. / Prophylaxie des infections dans les fractures ouvertes de jambe. Comparaison entre une dose de péfloxacine et 5 jours cefazoline-oxacilline. Etude randomisée sur 616 cas.

THE PURPOSE OF THE STUDY: Was to compare the efficacy of a single 800 mg injection of Pefloxacin (PF) versus 2 days of cefazolin (1 gr.Q.6 H) followed by 3 days of oxacillin (1 gr.Q.8 H) in patients with an open tibial fracture and to examine the predictive factors for infection. A double-blind double dummy, multicentric, randomized trial was performed. 616 adults with an open tibial fracture requiring single-stage bone coverage were included. The end point was wound infection within 3 months. RESULTS: Within 3 months, 21/316 patients were infected in the PF group (6.6 p. 100) versus 24/300 in the CZ-OX group (8 p. 100), the difference was not significant (95 p. 100 Cl for difference: -4.8 p. 100 to 2.1 p. 100). Twenty one strains were isolated in 18 infected patients in the PF group, and 27 in 20 patients in the CZ-OX group. Negative gram bacteria were less frequent in the PF group (10 p. 100) than in the CZ-OX group (48 p. 100), and positive gram bacteria were more frequent in the PF group (90 p. 100) than in the CZ-OX group (52 p. 100). Independent risk factors for infection were severe contamination, widespread contusion, unstable fracture, positive sample in the emergency room and at the end of surgery. Resistant infecting bacteria rate was 24 p. 100 in infected cases. CONCLUSION: There was no difference in infection rates after surgery for open tibial fractures between a 800 mg injection of Pefloxacin and 2 days of pephazolin followed by 3 days of oxacillin. Infecting bacteria were mainly nosocomially acquired.

Epidemiology of bacterial infection during management of open leg fractures.

In a randomised double-blind trial conducted between 1990 and 1994, 616 patients from 43 centres, pefloxacin (group P, 316 patients) and a cefazolin-oxacillin combination (group C, 300 patients) were compared in the prophylaxis of bone infection after grade 1 and 2 open leg fractures. Samples were obtained at emergency, before and during surgery, and from drain aspirates. Antimicrobial susceptibility, slime production and adherence properties of the bacteria were tested. Cultures at emergency and before surgery showed similar distributions of gram-positive and gram-negative bacteria in both groups, while wound closure and infecting isolates showed prevailing gram-positive bacteria in group P and gram-negative bacteria in group C. Positive cultures at each stage were correlated with the occurrence of infection but were not predictive of the infecting species, which were nosocomial bacteria in most cases. Positive cultures at wound closure warn of a higher infection risk. Twenty-one of 316 (6.6%) patients in group P and 24 of 300 (8%) in group C were considered infected within 3 months. The difference is not significant (chi-square test = 0.42; P = 0.51). Infecting strains were isolated from 38 patients (group P, 18; group C, 20). Infecting species, although not predictable, appear to be those escaping the spectrum of the prescribed antimicrobial prophylaxis.

Diagnosis of nosocomial pneumonia in cancer patients undergoing mechanical ventilation: a prospective comparison of the plugged telescoping catheter with the protected specimen brush.

STUDY OBJECTIVES: Quantitative culture of protected samples of lower respiratory tract secretions obtained by a fiberoptic protected specimen brush (PSB) is widely accepted for the diagnosis of ventilator-associated pneumonia (VAP), but this diagnostic procedure is time consuming, expensive, and may give rise to iatrogenic complications, especially in cancer patients who often present with thrombocytopenia. The plugged telescoping catheter (PTC) could be a satisfactory alternative to the PSB in this setting. The aim of the present study was to evaluate the interest of the PTC to diagnose VAP in ventilated cancer patients. DESIGN: A prospective observational study. SETTING: A 15-bed medical-surgical ICU in a comprehensive cancer center. PATIENTS AND INTERVENTIONS: Over a 9-month period, 42 patients suspected of having bacterial VAP during mechanical ventilation underwent 69 bronchial samplings: a blinded PTC and a fiberoptic PSB were performed successively in each case. A positive culture for both sampling procedures was defined as the recovery of > or = 10(3) cfu/mL of at least one potential pathogen. The PSB result was taken as the reference standard. MEASUREMENTS AND RESULTS: The overall agreement between the techniques was 87% (60/69). PTC had a sensitivity of 67%, a specificity of 93%, a positive predictive value of 71%, and a negative predictive value of 91%. CONCLUSIONS: We conclude that the accuracy of the blinded PTC compares well with that of the PSB for the diagnosis of VAP in cancer patients. The sensitivity of the PTC observed herein, which is slightly lower than that described in previous studies, may be due to the blinded nature of the method: the indications for initial or secondary coupling with a directed sampling method in patients with suspicion of localized pneumonia remain to be determined.

Reflections on gut decontamination in hematology.

In Europe, but decontamination (GD) is largely used in the prophylaxis of bacterial infections in departments of oncohematology treating neutropenic patients, in particular those patients subject to profound (absolute neutrophil count (ANC) <100/mm3) and prolonged (>10 days) neutropenia, such as patients undergoing bone marrow allografting or induction chemotherapy for acute leukemia. Initially, treatment was in the form of non-absorbable antibiotics, but this has been partially superseded by quinolone-containing regimens, in particular in the centers participating in EORTC trials. In the last two EORTC trials comparing different regimens for the treatment of febrile neutropenia, 57-73% of the patients were receiving GD. A French epidemiologic study, performed prospectively and consecutively in 36 oncohematology centers, has recently shown that 45% of febrile neutropenic patients receive digestive decontamination (DD) at the onset of their first febrile episode. The value of GD has been the subject of much controversy. Numerous trials, some of which were controlled, were performed in neutropenic patients in the 1980s, prior to trials of GD in intensive care units, but did not lead to a consensus in the medical community of the value of GD. Moreover, GD is not, or is infrequently, used in the USA. Apart from trials involving the quinolones, very few studies have been published during the last 10 years. Despite this, policies have not changed greatly in the various centers. The CLIOH group has gathered the opinions of experts invited to a multidisciplinary meeting that took place in Paris in October 1996. The text that follows summarizes the reflections arising from this forum. It should be noted that this meeting was not designed to be a consensus conference, but rather to re-examine the correlation between the data in the literature and actual clinical practice and to highlight the main problems posed by DD in current oncohematology. The experts were separated into three working groups, each of which has drafted a report which appears in the text below.

Earlier positivity of central-venous- versus peripheral-blood cultures is highly predictive of catheter-related sepsis.

To diagnose catheter-related sepsis without removing the catheter, we evaluated the differential positivity times of cultures of blood drawn simultaneously from central venous catheter and peripheral sites. In a 450-bed cancer reference center, simultaneous central- and peripheral-blood cultures were prospectively performed for patients with suspicion of catheter-related sepsis over an 18-month period. Data for 64 patients for whom the same microorganisms were found when central- and peripheral-blood samples were cultured were retrospectively reviewed by two independent physicians blinded to the differential positivity time values in order to establish or refute the diagnosis of catheter-related sepsis. The diagnosis was established in 28 cases, refuted in 14, and indeterminate in the remaining 22. The differential positivity time was significantly greater for patients with catheter-related sepsis (P < 10(-4)). A cutoff limit of +120 min had 100% specificity and 96.4% sensitivity for the diagnosis of catheter-related sepsis. These results strongly suggest that measurement of the differential positivity time might be a reliable tool facilitating the diagnosis of catheter-related sepsis in patients with an indwelling catheter.

Should cytomegalovirus be tested for in both blood and bronchoalveolar lavage fluid of patients at a high risk of CMV pneumonia after bone marrow transplantation?

To identify and treat patients at high risk of cytomegalovirus (CMV) pneumonia after bone marrow transplantation (BMT), we tested for CMV viraemia weekly, and performed broncho-alveolar lavage (BAL) on day 35 post-transplant in 63 recipients. 36 allogeneic BMT recipients were at a high risk of CMV pneumonia (25 CMV-seropositive recipients and 11 patients receiving marrow from a CMV-seropositive donor). Patients with a positive BAL or viraemia received a 14 d course of ganciclovir or foscarnet. CMV was detected in 29 (46%) of the 63 BMT recipients and excretion of CMV in blood and BAL was significantly linked. However, among the 29 patients who excreted the virus, only 10 (35%) shed CMV in blood and BAL at the same time: 19 patients (65%) had detectable CMV in blood (11 patients) or BAL (eight patients) only. Therefore, on the basis of viraemia or BAL alone, 21/29 patients (70%) and 18/29 patients (60%), respectively, would have received antiviral treatment. BAL increased the CMV detection rate by 13% (8/63 patients) relative to viraemia. With this strategy, the incidence of CMV pneumonia was reduced to 3% in allografted patients. Only two of the 19 autografted patients developed fatal CMV pneumonia. We avoided anti-CMV treatment in 54% of all the BMT recipients. In conclusion, CMV should be tested for in both blood and BAL fluid of BMT recipients at high risk of CMV pneumonia.

Should vancomycin be used empirically in febrile patients with prolonged and profound neutropenia? Results of a randomized trial.

OBJECTIVES: We conducted a randomized trial with ceftazidine alone or associated with amikacin or vancomycin to investigate the efficacy of the daily 3 g dosage of ceftazidime and the efficacy of monotherapy with ceftazidime and to determine if vancomycin should be added empirically. METHODS: Patient inclusion criteria were: age over 10 years, therapeutically-induced neutropenia and fever for at least three hours above 38.5 degrees C in absence of a clear non-infectious aetiology. Patients were randomized into three groups: group C, ceftazidime alone 3 g/day; group CA, ceftazidime 3 g/day plus amikacin 15 mg/kg/day; or group C, ceftazidime 3 g/day plus vancomycin 1.5 g/day. RESULTS: Results from one hundred and two episodes of fever were analyzed. The underlying diseases were haematological malignancies (89 patients) and solid tumours (13 patients). The median duration of neutropenia (< 0.5 x 10(9) PMN/L) was 18 days and the minimum duration of 7 days. The main criterion for the analysis of efficacy was the onset of a major infectious event, i.e. death related to documented or suspected infection and any infectious event considered life-threatening or hindering future treatment of the underlying disease. Eight (22%) patients in group C developed major infectious events compared with four (13%) in group CA and none in group CV (p < 0.01). Major infectious events were mainly due to Gram-positive organisms, particularly Streptococcus species. CONCLUSION: We conclude that: 1) ceftazidime alone and in association with amikacin is effective in preventing Gram-negative major infectious events; and 2) vancomycin should not be added only when a Gram-positive infection is documented, but used empirically.

Role of human microflora in health and disease.

The human host and its microbial flora constitute a complex ecosystem whose equilibrium serves as a remarkable example of reciprocal adaptation. Intestinal bacteria play an important role in the development of the immune system. The normal intestinal flora is responsible for resistance to colonization by exogenous pathogenic microorganisms. Nevertheless, it also constitutes a reservoir of potentially pathogenic bacteria in close contact with the host. These bacteria are responsible for opportunistic infections in immunocompromised hosts. The equilibrium of the flora can be upset by antibiotics, leading to infections as a result of proliferation of antibiotic-resistant pathogenic bacteria.

A reverse polymerase chain reaction method for detection of human cytomegalovirus late transcripts in cells infected in vitro.

A rapid and simple application of the polymerase chain reaction is described for the detection of human cytomegalovirus (HCMV) mRNAs in cells infected in-vitro. The method was first used to study the transcription of two HCMV genes, and confirm the link between the transcription of one, encoding for the major capsid protein, and viral replication. The oligonucleotides chosen in this region were specific for HCMV genome and sensitivity experiments showed that a single infected cell in 5 x 10(5) can be detected. Detection of this transcript should be suitable for diagnostic purposes, permitting the distinction between latency and active infection.

Close amino acid sequence relationship between the new plasmid-mediated extended-spectrum beta-lactamase MEN-1 and chromosomally encoded enzymes of Klebsiella oxytoca.

Isolated from an Escherichia coli strain MEN-1 is a plasmid-mediated beta-lactamase that confers resistance to methoxy imino third-generation cephalosporins. The protein purified to homogeneity was digested by trypsin, chymotrypsin and endoproteinase Asp-N. Amino acid sequence determinations of the resulting peptides gave rise to the alignment of the 263 residues of the beta-lactamase. From amino acid sequence comparison MEN-1 was found to share more than 72% identity with the chromosomally mediated beta-lactamases of Klebsiella oxytoca. Therefore, MEN-1 is the first transferable extended-spectrum beta-lactamase which is not directly derived from the widespread TEMs or SHV-1 penicillinases with which it presents less than 39% identity.

Kinetics of Saccharomyces cerevisiae elimination from the intestines of human volunteers and effect of this yeast on resistance to microbial colonization in gnotobiotic mice.

When healthy volunteers were given a daily dose of 3 x 10(8) life-dehydrated Saccharomyces cerevisiae cells for 5 days, the volunteers excreted 10(5) living yeast cells per g of feces at first, but the yeast cells disappeared within 5 days of the end of treatment. In gnotobiotic mice, S. cerevisiae administered alone colonized the intestinal tract but did not interfere with previous or subsequent colonization by a variety of potentially enteropathogenic microorganisms. When these microorganisms were present, the intestinal counts of S. cerevisiae were greatly reduced.

Risk factors for candidemia in patients with acute lymphocytic leukemia.

Between 1983 and 1987 the overall incidence of candidemia at the Institut Gustave Roussy, a tertiary care referral hospital for patients with cancer, increased from 0.1% (7 of 6,801) to 0.32% (24 of 7,515) (P = .009). Because acute lymphocytic leukemia (ALL) was the most common underlying disease in patients with candidemia, risk factors for candidemia were analyzed in this subset of patients. A case-control study comparing the eight ALL patients who had candidemia with 18 ALL control patients revealed that previous bacteremia, prolonged neutropenia, prolonged fever, prolonged administration of antimicrobial agents, treatment with multiple antimicrobial agents, and a relatively high concentration of Candida organisms in stool were significant risk factors for candidemia. In a logistic regression analysis, however, only receipt of vancomycin and/or imipenem was identified as an independent risk factor for candidemia. Further analysis showed that administration of vancomycin promoted proliferation of Candida organisms in the gastrointestinal tract and that this proliferation was associated with an increased risk of candidemia.