a Division of Microbiology b Infectious Diseases c Medical Oncology, Hospital Universitario 12 de Octubre , Madrid, Spain
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Abstract |
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Introduction |
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One of the potential problems with the use of fluoroquinolone prophylaxis is the selection of fluoroquinolone-resistant Gram-negative bacilli. There are now several reports which show an increase in the incidence of fluoroquinolone-resistant Gram-negative bacillus infections in cancer patients treated with quinolone antibacterial prophylaxis. 4,5,6 However, this problem has not been studied previously in patients treated with HDC and PBSCT. The aim of our study was to determine the incidence of quinolone-resistant Escherichia coli in faecal flora of patients with solid tumours treated with HDC and PBSCT ciprofloxacin prophylaxis, to assess the duration of colonization by resistant organisms and to analyse its clinical consequences.
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Patients and methods |
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Faecal samples were obtained from all patients at baseline and at the end of the prophylaxis. In
those patients with resistant strains, a new sample was obtained 3 months later. Stools were
collected in sterile containers and cultured within 2 h of collection. The specimens were plated
for qualitative culture by direct streaking. The culture media used were blood agar
(bioMérieux, Madrid, Spain), MacConkey agar (bioMérieux) and MacConkey
agar supplemented with 0.008 mg/mL of norfloxacin (Sigma Aldrich, Madrid, Spain). E.
coli isolates were identified and their susceptibilities were obtained by using automatic
methods (DIFCO PASCO, Difco Laboratories Inc., Detroit, MI, USA). The susceptibilities of all
fluoroquinolone-resistant strains were confirmed by disc diffusion. On the basis of the criteria of
the National Committee of Clinical Laboratory Standards,
7 E. coli was considered resistant to ciprofloxacin
when the MIC was 4 mg/L. Mean values of quantitative variables were compared with the
Students t-test, while the chi-squared test was employed to analyse categorical
data.
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Results |
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Fluoroquinolone-resistant E. coli strains were isolated from the faeces in 10 patients (32%) in the second stool sample. The MIC of ciprofloxacin in these isolates ranged from 8 to 64 mg/L. The characteristics of the patients that were colonized with resistant E. coli compared with those colonized with susceptible strains are outlined in the Table. The groups did not differ in any baseline characteristic. The mean number of days with prophylaxis was higher in patients that were colonized with E. coliresistant to fluoroquinolones compared with patients that remained colonized by susceptible strains (8.9 days vs 6.4 days). This difference, however, was not statistically significant. Both groups of patients had a favourable clinical course during their transplant procedure. The appearance of fluoroquinolone-resistant E. coliin faecal flora did not translate into a worse outcome in terms of longer duration of fever, antibiotic treatment, requirements of antifungal therapy or longer hospital stay. No other aerobic Gram-negative bacilli resistant to quinolones were isolated from faeces during the study period. One patient with breast cancer developed bacteraemia due to Serratia marcescens. This strain of S. marcescens was susceptible to fluoroquinolones and was also isolated from an iv cannula. No patient developed a bacteraemia due to a fluoroquinolone-resistant Gram-negative bacillus. Three patients had Staphylococcus epidermidis bacteraemia and one patient had a polymicrobial bacteraemia (S. epidermidisand Bacillusspp.).In most patients, colonization by resistant E. coli was transitory. Eight patients initially colonized with resistant flora harboured susceptible organisms in a third sample obtained 3 months after admission. The two patients that remained colonized with resistant strains in the third month had not received further treatment with quinolones.
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Discussion |
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Solid tumours, especially breast cancer, are the leading indication for HDC. Patients with solid tumours differ greatly from those with haematological malignancies in terms of past chemotherapy regimens, previous antibiotic treatment, conditioning HDC regimens and type of haematological rescue. Importantly, the use of PBSCT instead of bone marrow transplantation (BMT) with haematological growth factor support has reduced the length of neutropenia to a median of approximately 10 days. This is significantly shorter than in BMT. 2 All these factors have an important influence on the number and nature of infection complications during HDC. Quinolone-based prophylaxis has produced a dramatic decrease in the incidence of Gram-negative infections and outpatient treatment is commonly used in these patients. 3,9,10 The effect of prophylaxis on the susceptibility of E. coli to quinolones has not been previously addressed in these patients.
In our study no patient was found to be colonized with fluoroquinolone-resistant E. coli on initial sampling. This is not surprising since most of the patients had high risk breast cancer and were treated with HDC early in their disease. Most patients did not show neutropenia at this stage and, therefore, had not needed antibiotic treatment.
Ten patients were colonized by fluoroquinolone-resistant E. coli after a mean of 8 days on prophylaxis. This figure is quite similar to previous reports in patients with haematological malignancies and implies that fluoroquinolone-resistant E. coli can be selected even after short exposure to fluoroquinolones. There was a suggestion that the longer treatment with quinolones was associated with a higher risk of colonization with resistant E. coli; probably because of small patient numbers, this difference was not significant. We did not observe any differences in infectious complications in patients colonized with resistant flora compared with those with susceptible flora. In particular, we did not observe bacteraemia caused by fluoroquinolone-resistant E. coli. There is an increasing interest in giving multiple courses of chemotherapy in short periods of time to increase dose intensity. 9 In such situations the selection of fluoroquinolone-resistant flora during the first transplant might increase the incidence of resistant Gram-negative organisms present during the second course and offset the benefits of prophylaxis.
Patient colonization with fluoroquinolone-resistant E. coli was transitory. Only two patients remained colonized with resistant organisms. One of the major concerns with the unrestricted and widespread use of quinolones in the community is the increasing number of fluoroquinolone-resistant E. coli isolated (mainly from urine specimens). This number is estimated to be approximately 15% of urine cultures in Spain. 10 Given the recovery of normal fluoroquinolone-susceptible flora in many patients shortly after the transplantation, it is very unlikely that prophylaxis in this situation contributed significantly to this figure.
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Acknowledgments |
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Notes |
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References |
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Received 20 October 1998; returned 25 November 1998; revised 14 December 1998; accepted 17 March 1999