Letters
322
to the Editor
14. Coates D. Kelsey-Sykes Capacity test: origin evolution and current status. Pharm J 1977; 219: 4022403. 15. Best M, Sattar SA, Springthorpe VS, Kennedy ME. Efficacies of selected disinfectants against Mycobacterium tuberculosis. J Clin Microbial 1990; 28: 2234-2239. 16. Tyler R, Ayliffe GAJ. A surface test for virucidal activity of disinfectants: preliminary study with herpes virus. J Hasp Infect 1987; 9: 22-29. 17. Tyler R, Ayliffe GAJ, Bradley C. Virucidal activity of disinfectants: studies with the noliovirus. 7 Hoso Infect 1990: 15: 339-345. 18. Departmen; of health. Spills’of urine: potential risk of misuse of chlorine-releasing disinfecting agents. Safety Action Bulletin iXo 59. SAB (90) 41.
Sir
Enterococcus
faecium
sensitive
to teicoplanin
but not vancomycin
Teicoplanin is a glycopeptide antibiotic with a tetracyclic structure similar to the tricyclic Both glycopeptides inhibit one of vancomycin.’ peptidoglycan synthesis in Gram-positive organisms by binding close to the D-alanyl-D-alanine region of the side chains of peptidoglycan precursors.* Unlike vancomycin, teicoplanin is administered as an intravenous bolus, it is given in a single daily dose, and the risk of nephrotoxicity is very low.’ It is particularly useful in the treatment of serious Gram-positive infections in as the staphylococci or streptococci the immunocompromised patient, responsible are usually resistant to agents other than glycopeptides.’ Resistance to teicoplanin (MIC > 12 mg 1-i) of some coagulase-negative staphylococci has been reported from our own and other centres but most of these strains were sensitive to vancomycin (MIC 2 mg 1-‘).3,4 However, some strains of enterococci have high level resistance (MIC > 128 mg 1-i) to both glycopeptides, associated with production of a cytoplasmic membrane protein of molecular weight 39 kD.’ Others are susceptible to teicoplanin (MIC 2 mg 1-i) and resistant to vancomycin (MIC 64 mg l-‘), and growth in the presence of vancomycin induces synthesis of cytoplasmic membrane proteins of 39.5, 36.0, and 29.0 kD molecular weight.5,6 These strains were isolated from urine and were not associated with clinical disease. We report a case of bacteraemia with a vancomycin-resistant, teicoplanin-sensitive Enterococcus faecium. A 30-year-old man with chronic granulocytic leukaemia was admitted in July 1990 for cytotoxic chemotherapy and total body irradiation prior to marrow transplantation. Over the next month, he was given courses of ceftazidime, teicoplanin and ciprofloxacin for empirical treatment of fever during neutropenia. In the sixth week of admission, he received a match-unrelated bone marrow transplant. One week later, recurrence of his fever prompted treatment with ciprofloxacin, teicoplanin, amphotericin B and acyclovir. Coagulase-negative staphylococci were subsequently isolated from the blood. He responded clinically but developed jaundice and
Letters
323
to the Editor
diarrhoea as the result of graft-versus-host disease. Another episode of fever occasion, imipenem and, on this with was successfully treated Fusobacterium nucleatum was grown from culture of the blood. he remained neutropenic (WBC Four weeks after the transplant, 0.2 x lo9 1l.l) and a further febrile episode was treated with teicoplanin, amphotericin B and acyclovir. Coagulase-negative staphylococci were again isolated from the blood. The fever resolved but a different strain of coagulase-negative staphylococcus was isolated before antibiotics were stopped. A day later, he again became febrile and was treated with ceftazidime and gentamicin. A third strain of coagulase-negative staphylococcus was cultured from the blood before and during this course. All the isolates were sensitive to teicoplanin and vancomycin. From the last Enterococcus faecium was isolated. The set of peripheral blood cultures, Strep 714752) was resistant to ceftazidime (API organism (MIC > 128 mg l-i), gentamicin (MIC 16 mg l-l), azlocillin (MIC 128 mg l-l), ciprofloxacin (MIC 64 mg l-l), amikacin (MIC > 64 mg 1-i) and vancomycin (MIC> 64 mg 1-l). However, it was sensitive to teicoplanin (MIC 2 mg 1-l) and ramoplanin (MIC 0.5 mg 1-l). Treatment with teicoplanin (400 mg iv od) was restarted and two further blood cultures over the next week were negative. Despite evidence of engraftment, the patient then developed pneumonia, which was unresponsive to treatment, including liposomal amphotericin B, and he died 8 days later. At post-mortem, invasive aspergillosis affected the lungs, heart and liver. enterococci can be significant pathogens, Vancomycin-resistant particularly in the immune-suppressed patient who is repeatedly exposed to broad spectrum antibiotics. In some cases, teicoplanin could be an effective alternative. Although some workers’ demonstrate little or no induction of the susceptibility to teicoplanin must be self-resistance by teicoplanin, carefully monitored if infection persists. We thank
A. D. M. R.
Dr A.H.
Goldstone
for permission
to describe
P. R. Wilson Felmingham Robbins Chopra
this case.
Department of Clinical Microbiology, Department of eaematology, University College Hospital, London WClE 6AEU
References 1. Campoli-Richards DM, Brogden antibacterial activity, pharmacokinetic
RN, Faulds D. Teicoplanin. A review of its properties and therapeutic potential. Drugs 1990;
40: 449486. 2. Johnson AP, Uttley AHC, Woodford N, George RC. Resistance to vancomycin teicoplanin: an emerging clinical problem. Clin Microbial Rev 1990; 3: 280-291. 3. Wilson APR, O’Hare MD, Felmingham D, Griineberg RN. Teicoplanin-resistant coagulase negative staphylococcus. Lancet 1986; 2: 973.
and
324
Letters
to the Editor
4. Grant AC, Lacey RW, Brownjohn AM, Turney JH. Teicoplanin-resistant Lancet 1986; 2: 1166-l 167. coagulase-negative staphylococcus. 5. Woodford N, Johnson AP, Morrison D, Chin ATL, Stephenson JR, George RC. Two distinct forms of vancomycin resistance amongst enterococci in the UK. Lancet 1990; 1: 226. 6. Williamson R, Al-Obeid S, Shlaes JH, Goldstein FW, Shlaes DM. Inducible resistance to vancomycin in Enterococcusfaecium D366. J Infect Dis 1989; 1.59: 1095-l 104.
Sir, In-vitro susceptibility and clavulanic acid
of Xanfhomonas maltophilia as a test for the presumptive the species
to aztreonam identification of
is commonly implicated in clinical disease.’ the antimicrobial susceptibility of different strains of X.maZtophiZia has been reported2 and the treatment of infections caused by this organism can be difficult, since strains are often resistant to p-lactam and aminoglycoside antibiotics. 3 We have previously reported a difference in susceptibility to aminoglycosides at 30°C (most resistant) and at 37°C (most susceptible).4 Garcia-Rodriquez et al.” recently described synergism between aztreonam and clavulanic acid (2:l) against X.maZtophiZia. This prompted us to examine the potential use of this phenomenon as a test for the presumptive identification of the species. Bacteriostatic synergy between aztreonam and clavulanic acid was detected using a disc diffusion assay (aztreonam 30 ltg disc-‘, clavulanic acid 10 pg disc-‘) on DST agar (Oxoid) at 30°C (results were more reproducible at this temperature than at 37°C). Of the 43 organisms tested (Table I), only the 16 strains of X. maltophilia showed enhanced susceptibility to the antibiotic combination (Figure 1). Strains of Pseudomonas testosteroni did not show synergy between aztreonam and clavulanic acid but were uniquely susceptible to clavulanic acid alone. We believe, therefore, that the detection of in-vitro synergism between aztreonam and clavulanic acid could indeed be used for the identification of X.maltophilia. Xanthomonas
Variation
maltophilia
in
Table
I. Organism
Organism P.aeruginosa P.cepacia P. testosteroni P.pickettii P.stutzeri X.maltophilia
testedfor synergy between aztreonam clavulanic acid Numbers 8 13 4 1 1 16
and
Numbers showing synergy 0 0 0 0 0 16
322
to the Editor
14. Coates D. Kelsey-Sykes Capacity test: origin evolution and current status. Pharm J 1977; 219: 4022403. 15. Best M, Sattar SA, Springthorpe VS, Kennedy ME. Efficacies of selected disinfectants against Mycobacterium tuberculosis. J Clin Microbial 1990; 28: 2234-2239. 16. Tyler R, Ayliffe GAJ. A surface test for virucidal activity of disinfectants: preliminary study with herpes virus. J Hasp Infect 1987; 9: 22-29. 17. Tyler R, Ayliffe GAJ, Bradley C. Virucidal activity of disinfectants: studies with the noliovirus. 7 Hoso Infect 1990: 15: 339-345. 18. Departmen; of health. Spills’of urine: potential risk of misuse of chlorine-releasing disinfecting agents. Safety Action Bulletin iXo 59. SAB (90) 41.
Sir
Enterococcus
faecium
sensitive
to teicoplanin
but not vancomycin
Teicoplanin is a glycopeptide antibiotic with a tetracyclic structure similar to the tricyclic Both glycopeptides inhibit one of vancomycin.’ peptidoglycan synthesis in Gram-positive organisms by binding close to the D-alanyl-D-alanine region of the side chains of peptidoglycan precursors.* Unlike vancomycin, teicoplanin is administered as an intravenous bolus, it is given in a single daily dose, and the risk of nephrotoxicity is very low.’ It is particularly useful in the treatment of serious Gram-positive infections in as the staphylococci or streptococci the immunocompromised patient, responsible are usually resistant to agents other than glycopeptides.’ Resistance to teicoplanin (MIC > 12 mg 1-i) of some coagulase-negative staphylococci has been reported from our own and other centres but most of these strains were sensitive to vancomycin (MIC 2 mg 1-‘).3,4 However, some strains of enterococci have high level resistance (MIC > 128 mg 1-i) to both glycopeptides, associated with production of a cytoplasmic membrane protein of molecular weight 39 kD.’ Others are susceptible to teicoplanin (MIC 2 mg 1-i) and resistant to vancomycin (MIC 64 mg l-‘), and growth in the presence of vancomycin induces synthesis of cytoplasmic membrane proteins of 39.5, 36.0, and 29.0 kD molecular weight.5,6 These strains were isolated from urine and were not associated with clinical disease. We report a case of bacteraemia with a vancomycin-resistant, teicoplanin-sensitive Enterococcus faecium. A 30-year-old man with chronic granulocytic leukaemia was admitted in July 1990 for cytotoxic chemotherapy and total body irradiation prior to marrow transplantation. Over the next month, he was given courses of ceftazidime, teicoplanin and ciprofloxacin for empirical treatment of fever during neutropenia. In the sixth week of admission, he received a match-unrelated bone marrow transplant. One week later, recurrence of his fever prompted treatment with ciprofloxacin, teicoplanin, amphotericin B and acyclovir. Coagulase-negative staphylococci were subsequently isolated from the blood. He responded clinically but developed jaundice and
Letters
323
to the Editor
diarrhoea as the result of graft-versus-host disease. Another episode of fever occasion, imipenem and, on this with was successfully treated Fusobacterium nucleatum was grown from culture of the blood. he remained neutropenic (WBC Four weeks after the transplant, 0.2 x lo9 1l.l) and a further febrile episode was treated with teicoplanin, amphotericin B and acyclovir. Coagulase-negative staphylococci were again isolated from the blood. The fever resolved but a different strain of coagulase-negative staphylococcus was isolated before antibiotics were stopped. A day later, he again became febrile and was treated with ceftazidime and gentamicin. A third strain of coagulase-negative staphylococcus was cultured from the blood before and during this course. All the isolates were sensitive to teicoplanin and vancomycin. From the last Enterococcus faecium was isolated. The set of peripheral blood cultures, Strep 714752) was resistant to ceftazidime (API organism (MIC > 128 mg l-i), gentamicin (MIC 16 mg l-l), azlocillin (MIC 128 mg l-l), ciprofloxacin (MIC 64 mg l-l), amikacin (MIC > 64 mg 1-i) and vancomycin (MIC> 64 mg 1-l). However, it was sensitive to teicoplanin (MIC 2 mg 1-l) and ramoplanin (MIC 0.5 mg 1-l). Treatment with teicoplanin (400 mg iv od) was restarted and two further blood cultures over the next week were negative. Despite evidence of engraftment, the patient then developed pneumonia, which was unresponsive to treatment, including liposomal amphotericin B, and he died 8 days later. At post-mortem, invasive aspergillosis affected the lungs, heart and liver. enterococci can be significant pathogens, Vancomycin-resistant particularly in the immune-suppressed patient who is repeatedly exposed to broad spectrum antibiotics. In some cases, teicoplanin could be an effective alternative. Although some workers’ demonstrate little or no induction of the susceptibility to teicoplanin must be self-resistance by teicoplanin, carefully monitored if infection persists. We thank
A. D. M. R.
Dr A.H.
Goldstone
for permission
to describe
P. R. Wilson Felmingham Robbins Chopra
this case.
Department of Clinical Microbiology, Department of eaematology, University College Hospital, London WClE 6AEU
References 1. Campoli-Richards DM, Brogden antibacterial activity, pharmacokinetic
RN, Faulds D. Teicoplanin. A review of its properties and therapeutic potential. Drugs 1990;
40: 449486. 2. Johnson AP, Uttley AHC, Woodford N, George RC. Resistance to vancomycin teicoplanin: an emerging clinical problem. Clin Microbial Rev 1990; 3: 280-291. 3. Wilson APR, O’Hare MD, Felmingham D, Griineberg RN. Teicoplanin-resistant coagulase negative staphylococcus. Lancet 1986; 2: 973.
and
324
Letters
to the Editor
4. Grant AC, Lacey RW, Brownjohn AM, Turney JH. Teicoplanin-resistant Lancet 1986; 2: 1166-l 167. coagulase-negative staphylococcus. 5. Woodford N, Johnson AP, Morrison D, Chin ATL, Stephenson JR, George RC. Two distinct forms of vancomycin resistance amongst enterococci in the UK. Lancet 1990; 1: 226. 6. Williamson R, Al-Obeid S, Shlaes JH, Goldstein FW, Shlaes DM. Inducible resistance to vancomycin in Enterococcusfaecium D366. J Infect Dis 1989; 1.59: 1095-l 104.
Sir, In-vitro susceptibility and clavulanic acid
of Xanfhomonas maltophilia as a test for the presumptive the species
to aztreonam identification of
is commonly implicated in clinical disease.’ the antimicrobial susceptibility of different strains of X.maZtophiZia has been reported2 and the treatment of infections caused by this organism can be difficult, since strains are often resistant to p-lactam and aminoglycoside antibiotics. 3 We have previously reported a difference in susceptibility to aminoglycosides at 30°C (most resistant) and at 37°C (most susceptible).4 Garcia-Rodriquez et al.” recently described synergism between aztreonam and clavulanic acid (2:l) against X.maZtophiZia. This prompted us to examine the potential use of this phenomenon as a test for the presumptive identification of the species. Bacteriostatic synergy between aztreonam and clavulanic acid was detected using a disc diffusion assay (aztreonam 30 ltg disc-‘, clavulanic acid 10 pg disc-‘) on DST agar (Oxoid) at 30°C (results were more reproducible at this temperature than at 37°C). Of the 43 organisms tested (Table I), only the 16 strains of X. maltophilia showed enhanced susceptibility to the antibiotic combination (Figure 1). Strains of Pseudomonas testosteroni did not show synergy between aztreonam and clavulanic acid but were uniquely susceptible to clavulanic acid alone. We believe, therefore, that the detection of in-vitro synergism between aztreonam and clavulanic acid could indeed be used for the identification of X.maltophilia. Xanthomonas
Variation
maltophilia
in
Table
I. Organism
Organism P.aeruginosa P.cepacia P. testosteroni P.pickettii P.stutzeri X.maltophilia
testedfor synergy between aztreonam clavulanic acid Numbers 8 13 4 1 1 16
and
Numbers showing synergy 0 0 0 0 0 16
