Correspondence
Gram-posHhre infection in netrtropeak patients: gtycopeptMe antibiotic choice Sir, In their recent paper, Chomarat, Espinouse & Flandrois, (1991) are coming perilously close to suggesting using vancomycin instead of teicoplanin for the treatment of infections caused by coagulase-negative staphylococci on the basis of a unique technical problem. However, a comparative analysis of the characteristics of the two antibiotics suggests that teicoplanin may be a better choice than vancomycin for the combined therapy of Gram-positive infection in the neutropenic patient (Menichetti, 1990; Menichetti & Del Favero, 1991). Both compounds have similar antibacterial activity, except for some strains of coagulase-negative staphylococci (Staphylococcus haemolyticus and Staphylococcus epidermidis), which are more susceptible to vancomycin (Goldstein et al., 1990). Furthermore, previous treatment with a glycopeptide may be responsible for the emergence of resistance to teicoplanin in coagulase-negative staphylococci, as has been shown in strains isolated from neutropenic patients (Maugein et al., 1990). Both glycopeptide antibiotics are synergic 'in vitro' with, for example, aminogrycosides, which are usually a component of empiric antibiotic regimens. Although greater clinical experience has been gained with vancomycin, the efficacy of the two glycopeptides in the combined therapy of Gram-positive infections in neutropenic patients has been demonstrated to be similar (GIMEMA, 1991). In that multicentre trial
comparing patients treated with vancomycin or teicoplanin both combined with amil^c'" and ceftazidime, bacteraemias caused by coagulase-negative staphylococci were documented in 13 of 211 patients; all strains were susceptible to both glycopeptide antibiotics (inhibition zone diameter > 12 mm with a 30 fig disc) and therapy was considered successful in 4/7 patients treated with vancomycin and 5/6 patients receiving teicoplanin. Our previous experience with teicoplanin used in combination regimen for treating 122 febrile neutropenic patients gave similar results: the overall response rate was excellent as 88% of the patients (107/122) improved; it is noteworthy that all 14 coagulase-negative staphylococci bacteraemias were caused by strains susceptible to teicoplanin and were successfully treated (Menichetti et al., 1990). Vancomycin is potentially nephrotoxic, and factors found to be associated with increased risk were concurrent therapy with an aminoglycoside, length of treatment with vancomycin above 21 days, and vancomycin trough serum concentration above 10 mg/L (Rybak et al., 1990). Therefore, in neutropenic patients treated with vancomycin and an aminoglycoside, its seems advisable to monitor closely serum levels of both agents. Teicoplanin seems to be less toxic. Comparison of the nephrotoxic potential of the two glycopeptides in neutropenic patients treated with piperacinin, tobramycin and teicoplanin or vancomycin, revealed that nephrotoxicity occurred only in patients who received vancomycin (Kureishi et al., 1991). Furthermore, despite the fact that teicoplanin is administered by rapid (3-4 min) iv injection, hypotension rarely occurs and the characteristic 'red-man syndrome' described with vancomycin is seldom encountered (Sahai et al., 1990). Teicoplanin has the advantage of being much easier to administer, only one daily dose being required against the four (each given over 60 min) needed for vancomycin. In consequence, it saves valuable nursing time. The choice of the most appropriate dose and administration schedule for teicoplanin is of crucial importance. There seems to be a relationship between the dose, the peak scrum levels and the clinical effectiveness of teicoplanin. Most reported cases of teicoplanin treatment failures (Calain et al., 1987) are clearly related to insufficient dosage (i.e. 200 mg/daily). Increasing the dose of teicoplanin administered to infective endocarditis patients up to 7-14 mg/kg/day should guaran-
Downloaded from http://jac.oxfordjournals.org/ at University of California, Santa Barbara on June 22, 2015
Rodvold, K. A., Blum, R. A., Rscher, J. H., Zokufa, H. Z., Rotichafer, J. C , Crossley, K. B. et al. (1988). Vancomycin phannacokirtetics in patients with various degrees of renal function. Antimicrobial Agenli and Chemotherapy 32, 848-52. Rotschafer, J. C , Crossley, K., Zaske, D. E., Mead, K., Sawchuk, R. J. & Solan, L. D. (1982). Pharmacokinetics of vancomycin: observation in 28 patients and dosage recommendations. Antimicrobial Agents and Chemotherapy 22, 391-4. Soto, J., Sacristan, J. A. & Alsar, M. J. (1991). Necessity of a loading dose when using vancomycin in critical-ill patients. Journal of Antimicrobial Chemotherapy 27, 875. White, L. O., Edwards, R., Holt, H. A., Lovering, A. M., Finch, R. G. & Reeves, D. S. (1988). The in-vitro degradation at 37°C of vancomycin in serum, CAPD fluid and phosphate buffered saline. Journal of Antimicrobial Chemotherapy 22, 739-45.
461
462
Correspondence
htituto di Malaitie Infelliye, Ospedale Polidinico Regionale, 06100 Perugia. Italy
Menkhetti, F. (1990). Chairman's Summary. British Journal of Hatmalology 76, Suppt. 2, 57-9. Menichetti, F. & Del Favero, A. (1991). The role of Gram-positive therapy in the neutropenic patient Journal of Antimicrobial Chemotherapy 27, Suppl. B, 51-60. Menichetti, F. Del Favero, A., Bucaneve, G , Fiorio, M. & Aversa, F. (1990). Using teicoplanin for empirical therapy of febrile neutropenic patients with haematological malignancies. British Journal of HatmauAogy 76, Suppl. 2, 45-8. Rybak, M. J., Albrecht L. M., Boike, S. C. & Chandrasekar, P. H. (1990). Nephrotoxkity of vancomycin, alone and with an aminoglycoside. Journal of Antimicrobial Chemotherapy 25, 679-87. Sahai, J., Healy, D. P., Shehon, M. J., Miller, J. S., Ruberg, S. 1. &. Polk, R- (1990). Comparison of vancomycin- and tetcoplanin-induced hiitamine release and "red man syndrome". Antimicrobial Agents and Chemotherapy 34, 765-9.
References Calain, P., Krause, K. H., Vaudanx, P., Auchentaler, R., Lew, D., WaUvogel, F. et al. (1987). Early termination of a prospective, randomized trial comparing teicoplanin and flucloxacillin for treating severe staphylococcal infections. Journal of Infectious Diseases 155, 187-91. Chomarat M., Espinouse, D. & Flandrois, J. P. (1991). Coagulase-negative staphylococci emerging during teicoplanin therapy and problems in the determination of their sensitivity. Journal of Antimicrobial Chemotherapy 27, 475-80. Goldstein, F. W., Coutrot, A., Sieffer, A. & Acar, J. (1990). Percentage! and distribution of teicoplanin- and vancomycin-resistant strains among coagulase-negative staphylococci. Antimicrobial Agents and Chemotherapy 34, 899-900. Gnrppo Italiano Malattie Ematologkhe Mah'gne delTAduho (GIMEMA) (1991). Teicoplanin fT) vi vancomycin (V) as empiric therapy in febrile neutropenic patients. In Program and Abstracts of the Seventeenth International Congress of Chemotherapy, Berlin, 1991. Abstract 2179. Kureishi, A., Jewesson, P. J., Rubinger, M., Cole, G. D., Recce, D. E , Phillips, G. L. et al. (1991). Double-blind comparison of teicoplanin versus vancomycin in febrile neutropenic patients receiving concomitant tobramycin and piperacillin: effect on cyclosporin A associated nephrotoncity. Antimicrobial Agents and Chemotherapy 35, 2246-52. Martino, P., Venditti, M., Micozzi, A., Brandimarte, C , Gentile, G , Santini, C. el al. (1989). Teicoplanin in the treatment of Gram-positive bacterial endocarditis. Antimicrobial Agents and Chemotherapy 33, 1329-34. Maugein, J., PeDegrin, J. L., Brassard, G., Fourche, J., Leng, B. & Reiffen, J. (1990). In vitro activities of vancomycin and teicoplanin against coagulasenegative staphylococci isolated from nentropenk patients. Antimicrobial Agents and Chemotherapy 34, 901-3.
Reply Sir, We agree with the comments of Dr Menichetti concerning some advantages of teicoplanin compared to vancomycin in that it is easier to administer, better-tolerated and less toxic. In our previous paper (Espinouse & Chomarat, 1990), six patients experiencing reactions to vancomycin manifested as cutaneous allergy or nephrotoxicity were subsequently treated with teicoplanin without any evidence of crosssensitivity, although a patient with red man syndrome has been described recently (Dubettier et al., 1991). The spectrum of activity of teicoplanin is similar, but not identical to that of vancomycin. Certain coagulase-negative staphylococci such as Staphylococcus haemolyticus and some strains of Staphylococcus epidermidis are resistant to teicoplanin. In our paper (Chomarat, Espinouse & Flandrois, 1991), we wished to emphasize two problems, (i) Determination of in-vitro susceptibility of organisms to teicoplanin presents technical difficulties not associated with vancomycin; as infections due to Gram-positive bacteria, especially coagulasenegative staphylococci, increase in immunocompromised patients it would be better to resolve such technical problems. (i>) We reported three cases of septicaemia due to S. haemolyticus or S. epidermidis emerging during teicoplanin prophylactic therapy in neutropenic patients. Although in two cases the dosage given was considered insufficient, the risk of selecting for coagulase-negative staphylococci may be high during a period of
Downloaded from http://jac.oxfordjournals.org/ at University of California, Santa Barbara on June 22, 2015
tee higher serum levels and better therapeutic response (Martino et al., 1989). The increasing prevalence and changing resistance of Grampositive pathogens, as well as their poor response to an aminoglycoside plus 0-lactam regimen point to the need for specific antiGram-poative therapy in the treatment of the neutropenic patient Both vancomycin and teicoplanin have proved efficacious in the treatment of Gram-positive infections in the neutropenic patient. Vancomycin possesses greater in-vitro activity against coagulasenegative staphylococci, but teicoplanin possesses similar clinical efficacy, is less toxic and easier to administer. FRANCESCO MENICHETT1
Gram-posHhre infection in netrtropeak patients: gtycopeptMe antibiotic choice Sir, In their recent paper, Chomarat, Espinouse & Flandrois, (1991) are coming perilously close to suggesting using vancomycin instead of teicoplanin for the treatment of infections caused by coagulase-negative staphylococci on the basis of a unique technical problem. However, a comparative analysis of the characteristics of the two antibiotics suggests that teicoplanin may be a better choice than vancomycin for the combined therapy of Gram-positive infection in the neutropenic patient (Menichetti, 1990; Menichetti & Del Favero, 1991). Both compounds have similar antibacterial activity, except for some strains of coagulase-negative staphylococci (Staphylococcus haemolyticus and Staphylococcus epidermidis), which are more susceptible to vancomycin (Goldstein et al., 1990). Furthermore, previous treatment with a glycopeptide may be responsible for the emergence of resistance to teicoplanin in coagulase-negative staphylococci, as has been shown in strains isolated from neutropenic patients (Maugein et al., 1990). Both glycopeptide antibiotics are synergic 'in vitro' with, for example, aminogrycosides, which are usually a component of empiric antibiotic regimens. Although greater clinical experience has been gained with vancomycin, the efficacy of the two glycopeptides in the combined therapy of Gram-positive infections in neutropenic patients has been demonstrated to be similar (GIMEMA, 1991). In that multicentre trial
comparing patients treated with vancomycin or teicoplanin both combined with amil^c'" and ceftazidime, bacteraemias caused by coagulase-negative staphylococci were documented in 13 of 211 patients; all strains were susceptible to both glycopeptide antibiotics (inhibition zone diameter > 12 mm with a 30 fig disc) and therapy was considered successful in 4/7 patients treated with vancomycin and 5/6 patients receiving teicoplanin. Our previous experience with teicoplanin used in combination regimen for treating 122 febrile neutropenic patients gave similar results: the overall response rate was excellent as 88% of the patients (107/122) improved; it is noteworthy that all 14 coagulase-negative staphylococci bacteraemias were caused by strains susceptible to teicoplanin and were successfully treated (Menichetti et al., 1990). Vancomycin is potentially nephrotoxic, and factors found to be associated with increased risk were concurrent therapy with an aminoglycoside, length of treatment with vancomycin above 21 days, and vancomycin trough serum concentration above 10 mg/L (Rybak et al., 1990). Therefore, in neutropenic patients treated with vancomycin and an aminoglycoside, its seems advisable to monitor closely serum levels of both agents. Teicoplanin seems to be less toxic. Comparison of the nephrotoxic potential of the two glycopeptides in neutropenic patients treated with piperacinin, tobramycin and teicoplanin or vancomycin, revealed that nephrotoxicity occurred only in patients who received vancomycin (Kureishi et al., 1991). Furthermore, despite the fact that teicoplanin is administered by rapid (3-4 min) iv injection, hypotension rarely occurs and the characteristic 'red-man syndrome' described with vancomycin is seldom encountered (Sahai et al., 1990). Teicoplanin has the advantage of being much easier to administer, only one daily dose being required against the four (each given over 60 min) needed for vancomycin. In consequence, it saves valuable nursing time. The choice of the most appropriate dose and administration schedule for teicoplanin is of crucial importance. There seems to be a relationship between the dose, the peak scrum levels and the clinical effectiveness of teicoplanin. Most reported cases of teicoplanin treatment failures (Calain et al., 1987) are clearly related to insufficient dosage (i.e. 200 mg/daily). Increasing the dose of teicoplanin administered to infective endocarditis patients up to 7-14 mg/kg/day should guaran-
Downloaded from http://jac.oxfordjournals.org/ at University of California, Santa Barbara on June 22, 2015
Rodvold, K. A., Blum, R. A., Rscher, J. H., Zokufa, H. Z., Rotichafer, J. C , Crossley, K. B. et al. (1988). Vancomycin phannacokirtetics in patients with various degrees of renal function. Antimicrobial Agenli and Chemotherapy 32, 848-52. Rotschafer, J. C , Crossley, K., Zaske, D. E., Mead, K., Sawchuk, R. J. & Solan, L. D. (1982). Pharmacokinetics of vancomycin: observation in 28 patients and dosage recommendations. Antimicrobial Agents and Chemotherapy 22, 391-4. Soto, J., Sacristan, J. A. & Alsar, M. J. (1991). Necessity of a loading dose when using vancomycin in critical-ill patients. Journal of Antimicrobial Chemotherapy 27, 875. White, L. O., Edwards, R., Holt, H. A., Lovering, A. M., Finch, R. G. & Reeves, D. S. (1988). The in-vitro degradation at 37°C of vancomycin in serum, CAPD fluid and phosphate buffered saline. Journal of Antimicrobial Chemotherapy 22, 739-45.
461
462
Correspondence
htituto di Malaitie Infelliye, Ospedale Polidinico Regionale, 06100 Perugia. Italy
Menkhetti, F. (1990). Chairman's Summary. British Journal of Hatmalology 76, Suppt. 2, 57-9. Menichetti, F. & Del Favero, A. (1991). The role of Gram-positive therapy in the neutropenic patient Journal of Antimicrobial Chemotherapy 27, Suppl. B, 51-60. Menichetti, F. Del Favero, A., Bucaneve, G , Fiorio, M. & Aversa, F. (1990). Using teicoplanin for empirical therapy of febrile neutropenic patients with haematological malignancies. British Journal of HatmauAogy 76, Suppl. 2, 45-8. Rybak, M. J., Albrecht L. M., Boike, S. C. & Chandrasekar, P. H. (1990). Nephrotoxkity of vancomycin, alone and with an aminoglycoside. Journal of Antimicrobial Chemotherapy 25, 679-87. Sahai, J., Healy, D. P., Shehon, M. J., Miller, J. S., Ruberg, S. 1. &. Polk, R- (1990). Comparison of vancomycin- and tetcoplanin-induced hiitamine release and "red man syndrome". Antimicrobial Agents and Chemotherapy 34, 765-9.
References Calain, P., Krause, K. H., Vaudanx, P., Auchentaler, R., Lew, D., WaUvogel, F. et al. (1987). Early termination of a prospective, randomized trial comparing teicoplanin and flucloxacillin for treating severe staphylococcal infections. Journal of Infectious Diseases 155, 187-91. Chomarat M., Espinouse, D. & Flandrois, J. P. (1991). Coagulase-negative staphylococci emerging during teicoplanin therapy and problems in the determination of their sensitivity. Journal of Antimicrobial Chemotherapy 27, 475-80. Goldstein, F. W., Coutrot, A., Sieffer, A. & Acar, J. (1990). Percentage! and distribution of teicoplanin- and vancomycin-resistant strains among coagulase-negative staphylococci. Antimicrobial Agents and Chemotherapy 34, 899-900. Gnrppo Italiano Malattie Ematologkhe Mah'gne delTAduho (GIMEMA) (1991). Teicoplanin fT) vi vancomycin (V) as empiric therapy in febrile neutropenic patients. In Program and Abstracts of the Seventeenth International Congress of Chemotherapy, Berlin, 1991. Abstract 2179. Kureishi, A., Jewesson, P. J., Rubinger, M., Cole, G. D., Recce, D. E , Phillips, G. L. et al. (1991). Double-blind comparison of teicoplanin versus vancomycin in febrile neutropenic patients receiving concomitant tobramycin and piperacillin: effect on cyclosporin A associated nephrotoncity. Antimicrobial Agents and Chemotherapy 35, 2246-52. Martino, P., Venditti, M., Micozzi, A., Brandimarte, C , Gentile, G , Santini, C. el al. (1989). Teicoplanin in the treatment of Gram-positive bacterial endocarditis. Antimicrobial Agents and Chemotherapy 33, 1329-34. Maugein, J., PeDegrin, J. L., Brassard, G., Fourche, J., Leng, B. & Reiffen, J. (1990). In vitro activities of vancomycin and teicoplanin against coagulasenegative staphylococci isolated from nentropenk patients. Antimicrobial Agents and Chemotherapy 34, 901-3.
Reply Sir, We agree with the comments of Dr Menichetti concerning some advantages of teicoplanin compared to vancomycin in that it is easier to administer, better-tolerated and less toxic. In our previous paper (Espinouse & Chomarat, 1990), six patients experiencing reactions to vancomycin manifested as cutaneous allergy or nephrotoxicity were subsequently treated with teicoplanin without any evidence of crosssensitivity, although a patient with red man syndrome has been described recently (Dubettier et al., 1991). The spectrum of activity of teicoplanin is similar, but not identical to that of vancomycin. Certain coagulase-negative staphylococci such as Staphylococcus haemolyticus and some strains of Staphylococcus epidermidis are resistant to teicoplanin. In our paper (Chomarat, Espinouse & Flandrois, 1991), we wished to emphasize two problems, (i) Determination of in-vitro susceptibility of organisms to teicoplanin presents technical difficulties not associated with vancomycin; as infections due to Gram-positive bacteria, especially coagulasenegative staphylococci, increase in immunocompromised patients it would be better to resolve such technical problems. (i>) We reported three cases of septicaemia due to S. haemolyticus or S. epidermidis emerging during teicoplanin prophylactic therapy in neutropenic patients. Although in two cases the dosage given was considered insufficient, the risk of selecting for coagulase-negative staphylococci may be high during a period of
Downloaded from http://jac.oxfordjournals.org/ at University of California, Santa Barbara on June 22, 2015
tee higher serum levels and better therapeutic response (Martino et al., 1989). The increasing prevalence and changing resistance of Grampositive pathogens, as well as their poor response to an aminoglycoside plus 0-lactam regimen point to the need for specific antiGram-poative therapy in the treatment of the neutropenic patient Both vancomycin and teicoplanin have proved efficacious in the treatment of Gram-positive infections in the neutropenic patient. Vancomycin possesses greater in-vitro activity against coagulasenegative staphylococci, but teicoplanin possesses similar clinical efficacy, is less toxic and easier to administer. FRANCESCO MENICHETT1
