730
Correspondence
Rhodococcus and that it appeared to fit equally with the description given for R. erythropolis and R. ruber, but with four atypical carbon sources in each case. There was a total of
Cttnica Medea, Ospedale CMco, 6900 Lugano. Switzerland References Lipsky, B. A., Goldbergcr, A. C , Tomplrins, L. S. & Plorde, J. J. (1982). Infections caused by nondiphtheria Corynebacteria. Reviews of Infectious Diseases 4, 122O-3S. Harvey, R. L. & Sunstrum, J. C. (1991). Rhodococcus equi infection in patients with and without human immunodeficiency virus infection. Reviews of Infectious Diseases 13, 139-45. Van Etta, L. L., Filke, G. A., Ferguson, R. M. A Gerding, D. N. (1983). Corynebacterium equt a review of 12 cases of human infection. Reviews of Infectious Diseases 5, 1012-8. Saperfafectiom by EsckericUe coB rcsfetant to
fa patients J AntimicTob Chemother 1992; 3fc 730-731 Sir, Empirical antibiotic therapy with dprofloxadn in immunocompromised patients remains controversial (Johnson, Liu Yin & Tooth, 1980; EORTC International Antimicrobial Therapy Cooperative Group, 1991). A prospective randomized study of dprofloxadn vs ceftazidime-amikacin as empirical therapy in patients with haematological malignanties and severe neutropenia was undertaken at our hospital. Between January 1989 and May 1990 a total of 70 febrile episodes were treated with dprofloxadn (200 mg bd iv). Favourable initial responses were observed in 50% of the episodes and the global cure rate was 92-8%. These results were not different to those obtained in the ceftazidime-amikacin arm
Downloaded from http://jac.oxfordjournals.org/ at University of Manchester on May 18, 2015
twelve atypical tests against the description given for R. equi in Bergey's Manual. Since this seems to be a new species, isolated for the first time in Lugano, Switzerland, we propose the name R. luganensis. Acknowledgements. We are grateful to the staff of the Laboratorio Cantonale Batteriosierologico, Lugano (M. Dolina, C. Poloni, J. C. Piffaretti and R. PcduzzQ, to the Red Cross Centre, Lugano, and to Baxter SA for their prompt collaboration in the epidemiological investigation. F. de'CLARI T. MENGHIN1 G. BIAGGI P. MAGNOLI
(Diaz Mediavilla et al., 1991). Since then we have frequently used dprofloxadn, generally combined with vancomydn, as empirical therapy for febrile episodes in compromised hosts. During 1991 a high number of Escherichia coli strains resistant to dprofloxadn have been isolated from patients with haematological malignancies. Twenty-three percent of the E. coli strains isolated (9 out of 39) had MICs of dprofloxadn greater than 2 mg/L and were also resistant to norfloxadn, ofloxadn and pefloxadn. Six were isolated from blood cultures, two from urines and one from trachea! aspirate. In our department of haematology, 12 E. coli strains were isolated from blood cultures during 1991. Hence, 30% of bacteraemia due to E. coli could not be treated with fluoroquinolones in our hospital. Characteristics of the two groups of patients with fluoroquinolone-susceptible or -resistant E. coli strains isolated from blood cultures are shown in the Table. The main difference observed was longer prior therapy with dprofloxadn in patients with resistant strains with a median exposure of 35-5 days (range 10-77). In the subset with susceptible strains only two patients had received prior dprofloxadn therapy (for four and seven days, respectively). Degree of neutropenia, underlying disease, and days of hospitalization were not different between the two groups. None of the patients had suffered prior infection with E. coU or had received prophylactic norfloxadn for intestinal decontamination. We believe that most of our isolates were the result of resistant mutants from the endogenous flora (possibly of intestinal origin), selected by prior prolonged drug exposure. There are many reports describing Pseudomonas aeruginosa and Staphylococcus aureus strains resistant to quinolones (Acar & Francoual, 1990). Emergence of E. coll resistance during treatment with fluoroquinolones has been reported only occasionally (Wolfson & Hooper, 1989). However our experience suggests that prolonged therapy with fluoroquinolones can induce selection of resistant strains with the risk of development of serious systemic infections even with highly susceptible bacteria such as E, coli. Antibiotic monotherapy with fluoroquinolones in immunocompromised patients should not be maintained for long periods. Careful microbiological monitoring is needed for early detection of bacterial strains with abnormally high MICs in order to prevent lifethreatening complications.
731
Correspondence . Table. Characteristics of patients with, haematological malignancies and E. coli bacteraemia in 1991 Characteristics
E. coli susceptible to fluoroquinoloses
Number of patients Prior r^prr*fln^ffcm treatment Prior crproSoxacin exposure (days)
£. coli resistant to fluoroquinolones
6
6
2
4
4&7 each
median 35-5 range 10-77
co-trimoiazole: tetracyefine: Without any other
N. SOMOLINOS R. ARRANZ M. C. DEL REY M. L. JIMENEZ* Servicio de Microbiologia. Hospital de la Princesa. Diego de Leon 62. 28003 Madrid, Spain References Acar, J. F. & Francoual, S. (1990). The clinical problems of bacterial resistance to the new quinolonet. Journal of Antimicrobial Chemotherapy 26, Suppl. B, 207-13. EORTC International Antimicrobial Therapy Cooperative Group (1991). Prospective randomized evaluation of dprofloxacin versus piperadllin plus amikadn for empiric antibiotic therapy of febrile granulocytopenic cancer patients with rymphomas and solid tumors. Antimicrobial Agent* and Chemotherapy 35, 873-8. Diaz Mediavilla, J., Scaglione, C , Martinez, R., Vazquez, L., Figuera, A., Camara, R. el al. (1991). Estudk) prospectivo y ateatorizado de la eflcacia y tolerancia entre dprofloxacma y ceftaTirihna-amiVarinii para d tratamiento empirico de las infecdones en pscientes con hemopatias maKgnm y neutropenia grave. Revista Espakola de Quimioterapia 4, 37-42. Johnson, P. R. E , Uu Yin, J. A. & Tooth, J. A. (1990). High dose intravenous dprofloxacin in febrile neutropenic patients. Journal of Antimicrobial Chemotherapy 26, Supp/. F. 101-7. Wolfson, J. S. &. Hooper, D. C. (1989). Fhioroquinolone antimicrobial agents. Clinical Microbiological Reviews 2, 378-424. 'Corresponding author.
Human skin disposition of cefpodoxbne after oral administration of Its proxetfl ester
/ Antbnicrob Chemother 1992; 30: 731-733 Sir, Cefpodoxime proxctil (RU 51807), an orally active third generation cephalosporin, is the isopropoxy-carbonyloxyethyl ester of cefpodoxime. After oral administration, cefpodoxime proxetil is deesterified in the intestinal mucosa and absorbed into the bloodstream as cefpodoxime (RU 51763) (Hughes et al., 1989). The drug is resistant to various types of 0-lactamase and has good activity against Gram-positive and Gram-negative bacteria, particularly Streptococcus spp., Haemophitus influenzat, Neisseria gonorrhoeae, and Proteus mirabilis (Utsui, Inoue & Mitsuhashi, 1987; Wise et al., 1990). Because cefpodoxime proxetil has potential for the treatment of skin and soft tissue infections (Hoshino, Mogi & Takahashi, 1988), the aim of the present study was to investigate the distribution of the drug in human skin to assess if cefpodoxime achieves adequate therapeutic concentrations. Fourteen patients who were undergoing abdominal surgery were studied; all provided informed consent and the study was approved by the local Ethics Committee. Patients were given four oral doses of cefpodoxime proxetil 100 mg (expressed as cefpodoxime equivalents) at 12-h intervals and they had multiple skin and plasma samples taken between 30 min and 9 h after the last dose was administered. Normal skin was taken from the margins of the abdominal surgical wound.
Downloaded from http://jac.oxfordjournals.org/ at University of Manchester on May 18, 2015
Prior therapy with other intibiotics Resistance to other antibiotics:
Correspondence
Rhodococcus and that it appeared to fit equally with the description given for R. erythropolis and R. ruber, but with four atypical carbon sources in each case. There was a total of
Cttnica Medea, Ospedale CMco, 6900 Lugano. Switzerland References Lipsky, B. A., Goldbergcr, A. C , Tomplrins, L. S. & Plorde, J. J. (1982). Infections caused by nondiphtheria Corynebacteria. Reviews of Infectious Diseases 4, 122O-3S. Harvey, R. L. & Sunstrum, J. C. (1991). Rhodococcus equi infection in patients with and without human immunodeficiency virus infection. Reviews of Infectious Diseases 13, 139-45. Van Etta, L. L., Filke, G. A., Ferguson, R. M. A Gerding, D. N. (1983). Corynebacterium equt a review of 12 cases of human infection. Reviews of Infectious Diseases 5, 1012-8. Saperfafectiom by EsckericUe coB rcsfetant to
fa patients J AntimicTob Chemother 1992; 3fc 730-731 Sir, Empirical antibiotic therapy with dprofloxadn in immunocompromised patients remains controversial (Johnson, Liu Yin & Tooth, 1980; EORTC International Antimicrobial Therapy Cooperative Group, 1991). A prospective randomized study of dprofloxadn vs ceftazidime-amikacin as empirical therapy in patients with haematological malignanties and severe neutropenia was undertaken at our hospital. Between January 1989 and May 1990 a total of 70 febrile episodes were treated with dprofloxadn (200 mg bd iv). Favourable initial responses were observed in 50% of the episodes and the global cure rate was 92-8%. These results were not different to those obtained in the ceftazidime-amikacin arm
Downloaded from http://jac.oxfordjournals.org/ at University of Manchester on May 18, 2015
twelve atypical tests against the description given for R. equi in Bergey's Manual. Since this seems to be a new species, isolated for the first time in Lugano, Switzerland, we propose the name R. luganensis. Acknowledgements. We are grateful to the staff of the Laboratorio Cantonale Batteriosierologico, Lugano (M. Dolina, C. Poloni, J. C. Piffaretti and R. PcduzzQ, to the Red Cross Centre, Lugano, and to Baxter SA for their prompt collaboration in the epidemiological investigation. F. de'CLARI T. MENGHIN1 G. BIAGGI P. MAGNOLI
(Diaz Mediavilla et al., 1991). Since then we have frequently used dprofloxadn, generally combined with vancomydn, as empirical therapy for febrile episodes in compromised hosts. During 1991 a high number of Escherichia coli strains resistant to dprofloxadn have been isolated from patients with haematological malignancies. Twenty-three percent of the E. coli strains isolated (9 out of 39) had MICs of dprofloxadn greater than 2 mg/L and were also resistant to norfloxadn, ofloxadn and pefloxadn. Six were isolated from blood cultures, two from urines and one from trachea! aspirate. In our department of haematology, 12 E. coli strains were isolated from blood cultures during 1991. Hence, 30% of bacteraemia due to E. coli could not be treated with fluoroquinolones in our hospital. Characteristics of the two groups of patients with fluoroquinolone-susceptible or -resistant E. coli strains isolated from blood cultures are shown in the Table. The main difference observed was longer prior therapy with dprofloxadn in patients with resistant strains with a median exposure of 35-5 days (range 10-77). In the subset with susceptible strains only two patients had received prior dprofloxadn therapy (for four and seven days, respectively). Degree of neutropenia, underlying disease, and days of hospitalization were not different between the two groups. None of the patients had suffered prior infection with E. coU or had received prophylactic norfloxadn for intestinal decontamination. We believe that most of our isolates were the result of resistant mutants from the endogenous flora (possibly of intestinal origin), selected by prior prolonged drug exposure. There are many reports describing Pseudomonas aeruginosa and Staphylococcus aureus strains resistant to quinolones (Acar & Francoual, 1990). Emergence of E. coll resistance during treatment with fluoroquinolones has been reported only occasionally (Wolfson & Hooper, 1989). However our experience suggests that prolonged therapy with fluoroquinolones can induce selection of resistant strains with the risk of development of serious systemic infections even with highly susceptible bacteria such as E, coli. Antibiotic monotherapy with fluoroquinolones in immunocompromised patients should not be maintained for long periods. Careful microbiological monitoring is needed for early detection of bacterial strains with abnormally high MICs in order to prevent lifethreatening complications.
731
Correspondence . Table. Characteristics of patients with, haematological malignancies and E. coli bacteraemia in 1991 Characteristics
E. coli susceptible to fluoroquinoloses
Number of patients Prior r^prr*fln^ffcm treatment Prior crproSoxacin exposure (days)
£. coli resistant to fluoroquinolones
6
6
2
4
4&7 each
median 35-5 range 10-77
co-trimoiazole: tetracyefine: Without any other
N. SOMOLINOS R. ARRANZ M. C. DEL REY M. L. JIMENEZ* Servicio de Microbiologia. Hospital de la Princesa. Diego de Leon 62. 28003 Madrid, Spain References Acar, J. F. & Francoual, S. (1990). The clinical problems of bacterial resistance to the new quinolonet. Journal of Antimicrobial Chemotherapy 26, Suppl. B, 207-13. EORTC International Antimicrobial Therapy Cooperative Group (1991). Prospective randomized evaluation of dprofloxacin versus piperadllin plus amikadn for empiric antibiotic therapy of febrile granulocytopenic cancer patients with rymphomas and solid tumors. Antimicrobial Agent* and Chemotherapy 35, 873-8. Diaz Mediavilla, J., Scaglione, C , Martinez, R., Vazquez, L., Figuera, A., Camara, R. el al. (1991). Estudk) prospectivo y ateatorizado de la eflcacia y tolerancia entre dprofloxacma y ceftaTirihna-amiVarinii para d tratamiento empirico de las infecdones en pscientes con hemopatias maKgnm y neutropenia grave. Revista Espakola de Quimioterapia 4, 37-42. Johnson, P. R. E , Uu Yin, J. A. & Tooth, J. A. (1990). High dose intravenous dprofloxacin in febrile neutropenic patients. Journal of Antimicrobial Chemotherapy 26, Supp/. F. 101-7. Wolfson, J. S. &. Hooper, D. C. (1989). Fhioroquinolone antimicrobial agents. Clinical Microbiological Reviews 2, 378-424. 'Corresponding author.
Human skin disposition of cefpodoxbne after oral administration of Its proxetfl ester
/ Antbnicrob Chemother 1992; 30: 731-733 Sir, Cefpodoxime proxctil (RU 51807), an orally active third generation cephalosporin, is the isopropoxy-carbonyloxyethyl ester of cefpodoxime. After oral administration, cefpodoxime proxetil is deesterified in the intestinal mucosa and absorbed into the bloodstream as cefpodoxime (RU 51763) (Hughes et al., 1989). The drug is resistant to various types of 0-lactamase and has good activity against Gram-positive and Gram-negative bacteria, particularly Streptococcus spp., Haemophitus influenzat, Neisseria gonorrhoeae, and Proteus mirabilis (Utsui, Inoue & Mitsuhashi, 1987; Wise et al., 1990). Because cefpodoxime proxetil has potential for the treatment of skin and soft tissue infections (Hoshino, Mogi & Takahashi, 1988), the aim of the present study was to investigate the distribution of the drug in human skin to assess if cefpodoxime achieves adequate therapeutic concentrations. Fourteen patients who were undergoing abdominal surgery were studied; all provided informed consent and the study was approved by the local Ethics Committee. Patients were given four oral doses of cefpodoxime proxetil 100 mg (expressed as cefpodoxime equivalents) at 12-h intervals and they had multiple skin and plasma samples taken between 30 min and 9 h after the last dose was administered. Normal skin was taken from the margins of the abdominal surgical wound.
Downloaded from http://jac.oxfordjournals.org/ at University of Manchester on May 18, 2015
Prior therapy with other intibiotics Resistance to other antibiotics:
