Vancomycin versus placebo for treating persistent fever in patients with neutropenic cancer receiving piperacillin-tazobactam monotherapy.

This prospective, double-blind trial assessed whether the addition of a glycopeptide would be able to reduce the time to defervescence in neutropenic patients with cancer who had persistent fever 48-60 h after the initiation of empirical piperacillin-tazobactam monotherapy. Of 763 eligible patients, 165 with persistent fever were randomized to receive piperacillin-tazobactam therapy plus either vancomycin therapy or placebo. Defervescence was observed in 82 (95%) of 86 patients in the vancomycin group and in 73 (92%) of 79 patients in the placebo group (P=.52). The distributions of the time to defervescence were not statistically significant between the 2 groups (estimated hazard ratio, 1.03; 95% confidence interval, 0.75-1.43; P=.75). The number of additional episodes of gram-positive bacteremia and the percentage of patients for whom amphotericin B was empirically added to their therapy regimen were also similar in both groups. This study failed to demonstrate that the empirical addition of vancomycin therapy to the treatment regimen is of benefit to persistently febrile neutropenic patients with cancer.

Comparison of a solution of super-oxidized water (Sterilox) with glutaraldehyde for the disinfection of bronchoscopes, contaminated.

The efficacy of Sterilox, a super-oxidized water holding a reduction/oxidation potential of greater than 950 mV was compared with the efficacy of glutaraldehyde against clinical isolates of Mycobacterium tuberculosis and Mycobacterium avium-intracellulare. An in use method using an automated bronchoscope washing machine demonstrated that over five cycles, Sterilox with a contact time of 5 min gave log10 reduction factors for M. tuberculosis and M. avium-intracellulare of >6 and >5, respectively. Glutaraldehyde with a contact time of 10 min gave log10 reduction factors for both M. tuberculosis and M. avium-intracellulare of >4, and at a contact time of 20 min >5 each. The non-toxic nature of Sterilox, together with the reduction in viable counts demonstrated in this study, suggest that the solution is an effective alternative mycobactericidal agent to the established disinfectants for the disinfection of bronchoscopes and, therefore, justifies further investigation.

Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.

BACKGROUND: Intravenously administered antimicrobial agents have been the standard choice for the empirical management of fever in patients with cancer and granulocytopenia. If orally administered empirical therapy is as effective as intravenous therapy, it would offer advantages such as improved quality of life and lower cost. METHODS: In a prospective, open-label, multicenter trial, we randomly assigned febrile patients with cancer who had granulocytopenia that was expected to resolve within 10 days to receive empirical therapy with either oral ciprofloxacin (750 mg twice daily) plus amoxicillin-clavulanate (625 mg three times daily) or standard daily doses of intravenous ceftriaxone plus amikacin. All patients were hospitalized until their fever resolved. The primary objective of the study was to determine whether there was equivalence between the regimens, defined as an absolute difference in the rates of success of 10 percent or less. RESULTS: Equivalence was demonstrated at the second interim analysis, and the trial was terminated after the enrollment of 353 patients. In the analysis of the 312 patients who were treated according to the protocol and who could be evaluated, treatment was successful in 86 percent of the patients in the oral-therapy group (95 percent confidence interval, 80 to 91 percent) and 84 percent of those in the intravenous-therapy group (95 percent confidence interval, 78 to 90 percent; P=0.02). The results were similar in the intention-to-treat analysis (80 percent and 77 percent, respectively; P=0.03), as were the duration of fever, the time to a change in the regimen, the reasons for such a change, the duration of therapy, and survival. The types of adverse events differed slightly between the groups but were similar in frequency. CONCLUSIONS: In low-risk patients with cancer who have fever and granulocytopenia, oral therapy with ciprofloxacin plus amoxicillin-clavulanate is as effective as intravenous therapy.

A prospective study of wound infection in coronary artery surgery.

OBJECTIVE: The incidence of wound infection in coronary artery surgery is low, but there is an appreciable mortality associated with sternal infection. In other fields of surgery there is evidence that an all disposable paper gown and drape system has protective advantages over a fabric system. Using an established wound scoring system (ASEPSIS), we investigated this in a prospective, randomised trial of patients undergoing cardiac surgery. METHODS: 505 patients undergoing isolated coronary artery surgery in a single hospital over an 18 month period were randomised to either a disposable, paper drape system or re-usable fabric drapes. Allocation was stratified according to whether or not the patient had had previous coronary artery surgery. Patients were followed for 3 months. Total infection scores for each wound were calculated from daily scores collected in hospital together with the scores at six weeks and three months. RESULTS: The two randomised groups were otherwise well matched. Full follow-up information was available for 464 (92%) patients. There was no evidence of any difference in rates of sternal or leg wound infection between the two groups (P = 0.87 and 0.62, respectively). Women were more likely to have infected sternal wounds (P = 0.17) and significantly more likely to have infected leg wounds (P = 0.04). Patients with sternal wound infections had a significantly higher body mass index (P = 0.001). High Parsonnet scores and increased time on ventilation were significantly associated with leg wound but not sternal infections. For both wound sites, patients with infections had spent longer in the operating theatre. CONCLUSION: In a randomised controlled study of patients undergoing coronary artery surgery we found that the use of paper drapes and gowns conferred no benefit over a reusable fabric in terms of post-operative wound infection. Although females and diabetics are more likely to experience this complication, an important additional risk factor is an extended operating time.

Methicillin-resistant Staphylococcus aureus: impact at a national cystic fibrosis centre.

In many patient populations there has been a progressive increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA). We examined the prevalence and consequences of acquiring MRSA in the adult cystic fibrosis (CF) population at Royal Brompton. Patients who became colonized by MRSA between 1965 and 1997 were identified from an existing database and case-notes were reviewed. Clinical and microbiological data were recorded. Twenty-six patients became colonized with MRSA during this period. Median age at acquisition was 23.4 years (range 11.8-43.3 years) and median FEV1 (percent predicted) was 28.9% (range 12-81%). Twenty patients (77%) had an FEV1 of < or = 40% predicted MRSA was probably acquired by four patients at Royal Brompton. In 17 patients isolates wer first identified whilst under the care of a total of 11 other institutions. Since the first case of MRSA infection in 1982, there has been an increase in prevalence to a current rate of nine cases in the first seven months of 1997. The commonest site of colonization was the lower airway (96%); the nose (23%) and skin sites (15%) were more rarely affected. Duration of colonization was frequently brief with nine cases (35%) lasting less than one month. The identification of MRSA appeared to be of little clinical significance, and did not generally affect outcomes. Only three patients were MRSA positive at the time of death, and in only one of these was MRSA considered a possible contributing factor.

Comparison of three monoclonal antibody pools for the detection of respiratory viral antigen in respiratory secretions.

The aim of this study was to compare the sensitivities of commercial monoclonal antibody pools to be used as an initial rapid screen for detection of viral antigens in respiratory secretions. The availability of commercial monoclonal antibodies has dramatically improved the detection of viruses by immunofluorescence techniques in exfoliated cells obtained from respiratory secretions. Several companies have recently introduced monoclonal antibody pools to detect the presence of respiratory viruses in a single preparation. Ninety-four stored slide preparations that had previously been examined by individual monoclonal antibodies were tested using three commercial monoclonal antibody pools produced by Sanofi (UK), Dako (UK), and Quadratech (UK). These monoclonal antibody pools had a sensitivity of 79.6%, 90.9%, and 100%, respectively, when compared with the original results. The overall intensity of immunofluorescence was also examined.

A comparison of outcome from febrile neutropenic episodes in children compared with adults: results from four EORTC studies. International Antimicrobial Therapy Cooperative Group (IATCG) of the European Organization for Research and Treatment of Cancer (EORTC).

The object of this study was to determine whether there were any differences between the 'typical' child with fever and neutropenia and their adult counterpart with regard to infection type and outcome, by analysis of 3080 patients, including 759 children < 18 years of age and 2321 adults. These represented patients randomized in previous trials, between 1986 and 1994, which compared empirical antibiotic regimens for fever in neutropenic patients. There were fewer childhood acute myeloid leukaemia patients than adults but more acute lymphoblastic leukaemia cases and more with solid tumours undergoing intensive myelosuppressive therapy. The children were less likely to be undergoing first induction therapy but the relative incidence of patients receiving relapse schedules or maintenance therapies were not significantly different in the two age groups. Children less frequently had a defined site of infection than adults and where they had a defined site there were more upper respiratory tract but fewer lung infections. There was a similar low incidence of shock at presentation in the two groups but the children's median neutrophil count was lower, and their median duration of granulocytopenia before the trial was shorter. The incidence of bacteraemia was similar, but clinically documented infection was less frequent and fever of unknown origin consequently more common in children. Children developed more streptococcal bacteraemias and fewer staphylococcal bacteraemias than adults (P=0.003) but the relative incidence of various gram-negative species was similar (P=0.57). In general, the children had a better overall success rate and lower mortality than adults. Death from infection was only 1% in children versus 4% in adults (P=0.001), and time to defervescence was shorter in children. In the younger age group, univariate logistic regression models showed high temperature, prolonged neutropenia before the trial and shock as prognostic indicators for the presence of bacteraemia. Solid tumour patients were significantly less likely to have a bacteraemia. Multivariate analysis confirmed the independent prognostic value of these indicators. Using the logistic equation of the selected model, the overall discriminant ability was poor. However, it was possible to identify a small subgroup without shock or high fever and with a short prior duration of neutropenia which carries a particularly low risk of bacteraemia, who could be considered for early discharge, monotherapy and shortened courses of antibodies, in prospective trials.

Disinfection of bronchoscopes, contaminated in vitro with Mycobacterium tuberculosis, Mycobacterium avium-intracellulare and Mycobacterium chelonae in sputum, using stabilized, buffered peracetic acid solution ('Nu-Cidex').

The efficacy of 0.35% stabilized buffered peracetic acid solution ('Nu-Cidex') against clinical isolates of Mycobacterium tuberculosis, Mycobacterium avium-intracellulare and Mycobacterium chelonae in homogenized sputum was tested. An in-use method, using an automated bronchoscope washing machine, showed that over 10 cycles, at a disinfectant contact time of 5 min, M. tuberculosis and M. chelonae were effectively eradicated from the bronchoscope, even in the absence of detergent and pre-cleaning. M. avium-intracellulare was not eradicated in only one of 10 cycles with contact times of 5 and 10 min, but numbers were reduced by > 7 log10 and > 5 log10, respectively. With detergent present, M. avium-intracellulare was successfully eradicated in all cycles at a contact time of 5 min or greater. The results demonstrate that peracetic acid is an effective mycobactericidal agent for use in the disinfection of bronchoscopes.

Evaluation of a commercial radiometric system for primary isolation of mycobacteria over a fifteen-year period.

The rate of recovery and time to detection of mycobacteria from clinical specimens were analysed for specimens inoculated into both radiometric Middlebrook 7H12 (Bactec 12B, originally 12A) medium and Lowenstein-Jensen egg-based medium (with and without sodium pyruvate) over the 15-year period from 1980 to 1994. A total of 19,679 Bactec vials were inoculated together with Lowenstein-Jensen slopes, with 2198 mycobacterial isolates detected. The mean times to detection for Bactec and Lowenstein-Jensen were 11.7 days and 23.9 days, respectively. In 195 cases mycobacteria were isolated from Bactec and not from Lowenstein-Jensen, whereas the reverse was true in 42 cases. The number of contaminated Bactec vials was 488 and the number of contaminated Lowenstein-Jensen slopes 448.

Treatment of endocarditis with teicoplanin: a retrospective analysis of 104 cases.

Infective endocarditis is an uncommon disease but retains a high mortality. Glycopeptides are used for patients with resistant pathogens, those allergic to penicillins or for those outside the hospital. The once daily administration of teicoplanin and its low toxicity suggest that it would be suitable for use in the long courses required for endocarditis. However, the dosage and combinations to be used require further study. A retrospective review has been made of 104 episodes of endocarditis treated with teicoplanin in 101 patients seen over 7 years. Most patients had been referred to major London hospitals following failure of medical treatment. After three loading doses of 400 mg, teicoplanin was given at a dose of 400 mg/day in combination with other antibiotics such as gentamicin. Follow up was for one year. The most common pathogens were Streptococcus sanguis (15 cases), Staphylococcus aureus (13 cases) and Staphylococcus epidermidis (10 cases). Of 80 patients febrile at the start of treatment with teicoplanin, 63 (79%) lost their fever within a median of 2 days (1-35 days). Cure without surgery was effected in 50 (48%) and 75% of patients survived. Other antibiotics, usually gentamicin or rifampicin, were used in 92 (90%) of patients. Two strains of Streptococcus spp. were said to be resistant but there was no relationship between MIC of teicoplanin and outcome. Pathogens with a high MBC tended to be more likely to resist treatment. Adverse effects resulted in the withdrawal of teicoplanin in 20 cases (19%) but most events were mild and renal deterioration occurred in only five patients. Teicoplanin was effective in the treatment of endocarditis and appeared to be safe given the severity of disease in the patients treated.

Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto Infection Program.

Combinations of beta-lactams plus aminoglycosides have been standard therapy for suspected infections in granulocytopenic cancer patients, especially those with profound long-lasting granulocytopenia. With the advent of new broad-spectrum bactericidal antibiotics such as extended-spectrum cephalosporins or carbapenems, the need to combine beta-lactams with aminoglycosides became more controversial. The objective of this prospective randomized multicenter study was to compare the efficacy, safety, and tolerance of meropenem monotherapy with those of the combination of ceftazidime plus amikacin for the empirical treatment of fever in granulocytopenic cancer patients. Of 1,034 randomized patients, 958 were assessable in the intent-to-treat analysis for response to antibacterial therapy, including 483 in the meropenem group and 475 in the ceftazidime-plus-amikacin group. The median durations of neutropenia were 16 and 17 days, respectively. A successful outcome was reported in 270 of 483 (56%) patients treated with monotherapy compared with 245 of 475 (52%) patients treated with the combination group (P = 0.20). The success rates in the monotherapy group and the combination group were similar by type of infection (single gram-negative bacteremia, single gram-positive bacteremia, clinically documented infection, and possible infection). The occurrence of further infections assessed in patients for whom the allocated regimen was not modified did not differ between the two groups (12% in both groups). Mortality due to the presenting infection or further infection was relatively low (8 patients treated with the monotherapy compared with 13 patients treated with the combination). A total of 1,027 patients were evaluable for adverse events; the proportion of those who developed adverse effects was similar between the two groups (29% in both groups), and only 19 (4%) patients in the monotherapy group and 31 (6%) in the combination group experienced an adverse event related or probably related to the study drug. Allergic reactions were the only reason for stopping the protocol antibiotic(s) (3 and 5 patients, respectively). This study confirms that monotherapy with meropenem is as effective as the combination of ceftazidime plus amikacin for the empiric treatment of fever in persistently granulocytopenic cancer patients, and both regimens were well tolerated.

Comparison of characteristics of patients and treatment outcome for pulmonary non-tuberculous mycobacterial infection and pulmonary tuberculosis.

BACKGROUND: Patients with non-tuberculous mycobacteria are usually started on conventional antituberculous triple therapy once acid fast bacilli are detected, before the exact type of mycobacteria has been identified. The ability to identify the characteristics of patients with tuberculous and non-tuberculous mycobacteria may be helpful in identifying before treatment those patients more likely to have non-tuberculous infection. METHODS: A retrospective study was conducted of all patients in one unit in whom non-tuberculous mycobacteria were identified in sputum or bronchoalveolar washings in the period 1987-93. The pattern of drug resistance was determined from laboratory records, and all case notes and chest radiographs were reviewed to identify the underlying disease and treatment outcome. All cases were compared with a matched control group of patients with culture positive Mycobacterium tuberculosis diagnosed during the same period. RESULTS: In the period studied there were 70 non-tuberculous and 221 tuberculous isolates. The non-tuberculous bacteria were typed as follows: M xenopi 23 (33%), M kansasii 19 (27%), M fortuitum 14 (20%), others 14 (20%). Of those with non-tuberculous mycobacteria, 83% were white subjects compared with 47% for tuberculosis. Patients with non-tuberculous mycobacteria were older than those with tuberculosis. Pre-existing lung disease or AIDS was present in 81% of patients with non-tuberculous mycobacteria and in 17% of patients with tuberculosis. Sensitivity to rifampicin and ethambutol was seen in 95% of M xenopi and 96% of M kansasii isolates. Relapse occurred in 60% of cases infected with M xenopi, 20% infected with M kansasii, and in 7% of cases with tuberculosis. CONCLUSIONS: In the population studied non-tuberculous mycobacteria occurred most frequently in elderly white subjects with pre-existing lung disease. If mycobacteria are detected in this group, consideration should be given to the possibility of non-tuberculous infection before embarking on treatment. A combination containing rifampicin and ethambutol is effective. The relapse rate for infection with M xenopi is high and prospective studies of the effect of the above combination of antituberculosis drugs are needed.

The efficacy of the disinfection of bronchoscopes contaminated in vitro with Mycobacterium tuberculosis and Mycobacterium avium-intracellulare in sputum: a comparison of Sactimed-I-Sinald and glutaraldehyde.

The efficacy of Sactimed-I-Sinald and glutaraldehyde was tested against clinical isolates of Mycobacterium tuberculosis (MTB) and Mycobacterium avium-intracellulare (MAI). An in-use method demonstrated that over 10 disinfection cycles, using an auto-disinfector and a contact time of 60 min, MTB was eradicated in 10 out of 10 cycles with Sactimed-I-Sinald and five out of 10 cycles for glutaraldehyde. For MAI, Sactimed-I-Sinald showed a 5 log reduction at a 60 min contact time, which was not seen with glutaraldehyde. Although further evaluation is necessary, Sactimed-I-Sinald appears a promising alternative to glutaraldehyde.

Piperacillin-tazobactam plus amikacin versus ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.

Gram-positive bacteria have become the predominant infecting organisms in granulocytopenic cancer patients. Empiric antibiotic regimens used in febrile neutropenic patients often include an extended-spectrum cephalosporin, but the response to therapy in gram-positive coccal bacteremia has been unsatisfactory. Thus, new antibiotics with better activity against gram-positive bacteria should be tested. The objective of this prospective randomized controlled study was to evaluate and compare the efficacy and tolerance of piperacillintazobactam plus amikacin with that of ceftazidime plus amikacin, the standard regimen of the International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer, in the empiric treatment of febrile granulocytopenic cancer patients. A total of 858 episodes were eligible for this study, and 706 episodes were assessable for efficacy. The antibiotic treatment was successful in 210 (61%) of 342 episodes in the piperacillin-tazobactam-amikacin group compared with 196 (54%) of 364 episodes treated with ceftazidime plus amikacin (P = 0.05). The time to defervescence was significantly shorter (P = 0.01) and the time to failure was significantly longer (P = 0.02) in the piperacillin-tazobactam-amikacin group. A significant difference in response to bacteremic infections between the two patient groups was found: piperacillin-tazobactam plus amikacin was successful in 40 of 80 episodes (50%), and ceftazidime plus amikacin was successful in 35 of 101 episodes (35%) (P = 0.05). A multivariate analysis showed that the probability of failure was significantly greater with ceftazidime plus amikacin than with piperacillin-tazobactam plus amikacin (P = 0.02). This trial suggests that piperacillin-tazobactam plus amikacin is more effective than ceftazidime plus amikacin for the empiric treatment of fever and bacteremia in granulocytopenic cancer patients. Although cutaneous reaction was more frequently associated with piperacillin-tazobactam plus amikacin than with ceftazidime-amikacin, this unwanted effect was relatively mild and its incidence was comparable to that of other penicillin compounds.

Characteristics of patients with drug resistant and drug sensitive tuberculosis in East London between 1984 and 1992.

BACKGROUND: The aim of this study was to investigate retrospectively factors associated with drug resistant tuberculosis at the London Chest Hospital. METHODS: The microbiology results for patients with tuberculosis at the hospital for the period 1984-92 were reviewed, together with case notes and chest radiographs of all patients with drug resistant tuberculosis and of 101 patients with drug sensitive tuberculosis notified during the same period as a control group. RESULTS: Culture positive pulmonary tuberculosis occurred in 292 patients. Drug resistant strains were isolated from 20 patients (6.8%). Ten of the 292 (3.4%) had strains resistant to a single drug and nine (3.1%) had resistance to more than one first line drug. One patient had strains resistant to isoniazid and capreomycin. Strains resistant to more than one drug were all resistant to isoniazid and rifampicin. In five patients these strains were also resistant to pyrazinamide and in two they were resistant to streptomycin. Single drug resistant strains were resistant to isoniazid (nine patients) or streptomycin (one patient). Among the risk factors studied previous treatment for tuberculosis was the most significant association with drug resistant tuberculosis (7/9) for patients with resistance to more than one drug; 5/11 for single drug resistance compared with 6/101 patients in the drug sensitive group (odds ratio 22.8). Other risk factors were bilateral disease at presentation (odds ratio 8.5), and disease at a young age (odds ratio 1.03). CONCLUSIONS: Previous treatment for tuberculosis and bilateral disease at presentation were found to be more commonly associated with cases of drug resistant than with drug sensitive tuberculosis.

Colonisation of lung allografts with Pseudomonas aeruginosa in heart-lung transplant recipients with cystic fibrosis.

Six patients (four with cystic fibrosis, two with bronchiectasis) harboured Pseudomonas aeruginosa in the lung before heart-lung transplantation. Three of the patients with cystic fibrosis were colonised by strains of different genotype postoperatively, and the colonisation tended to be short lived.