Moxifloxacin for Community-Acquired Pneumonia
LETTER+, http://www.100md.com
I read with great interest the moxifloxacin versus co-amoxiclav study in the June issue of Antimicrobial Agents and Chemotherapy (2). It is one of the very rare randomized controlled trials on the treatment of community-acquired pneumonia (CAP) that included a significant amount of severely ill patients and pretreated patients and that showed superiority in an intent-to-treat, as well as in an on-treatment, analysis.+, http://www.100md.com
However, it remains unclear if the superiority of moxifloxacin is a consequence of better coverage of the so called "atypical agents," the increased effectiveness in patients with penicillin-resistant pneumococci, the choice of treatment in the control group, or any other reason. A further analysis of the data might therefore be instructive. It would be interesting to know if the difference in outcome between the two study groups is equally, not, or possibly more apparent in patients pretreated and those not pretreated with antibiotics? Is the difference in outcome between the two study groups clearer in those patients in whom any etiologic agent was demonstrated than in those in whom no agent was found?
Very few CAP studies include a significant number of severely ill patients, and therefore, very little evidence from randomized controlled trials is available to guide the management of patients treated in intensive care units (ICUs). Possibly, the moxifloxacin study might give valuable information. Therefore, it would be interesting to know how many of the patients studied were treated in the ICU and how many of them were ventilated during hospitalization. Was the difference in outcome the same in this subgroup of critically ill CAP patients?5h}{&q, 百拇医药
Finally, it is important to remember that although 36% of the patients included in the trial were pretreated with antibiotics (as is the case for "real-life" hospitalized CAP patients), patients pretreated with a fluoroquinolone were excluded and therefore no conclusions about the effectiveness of moxifloxacin in this setting can be drawn. Avoidance of fluoroquinolones as the treatment of choice in this setting may be important (1, 3).
REFERENCES.x?@^, http://www.100md.com
Davidson, R., R. Cavalcanti, J. L. Brunton, D. J. Bast, J. C. de Azavedo, P. Kibsey, C. Fleming, and D. E. Low. 2002. Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N. Engl. J. Med. 346:747-750..x?@^, http://www.100md.com
Finch, R., D. Schürmann, O. Collins, R. Kubin, J. McGivern, H. Bobbaers, J. L. Izquierdo, P. Nikolaides, F. Ogundare, R. Raz, P. Zuck, and G. Höffken. 2002. Randomized controlled trial of sequential intravenous (i.v.) and oral moxifloxacin compared with sequential i.v. and oral co-amoxiclav with or without clarithromycin in patients with community-acquired pneumonia requiring initial parenteral treatment. Antimicrob. Agents Chemother. 46:1746-1754..x?@^, http://www.100md.com
Ho, P. L., W. S. Tse, K. W. Tsang, T. K. Kwok, T. K. Ng, V. C. Cheng, and R. M. Chan. 2001. Risk factors for acquisition of levofloxacin-resistant Streptococcus pneumoniae: a case-control study. Clin. Infect. Dis. 32:701-707..x?@^, http://www.100md.com
Authors' Reply.x?@^, http://www.100md.com
LETTER.x?@^, http://www.100md.com
B. J. A. Rijnders raises several interesting points regarding the CAP study we reported recently (2). This CAP study demonstrated significant superiority of intravenous-to-oral (i.v./p.o.) moxifloxacin monotherapy to i.v./p.o. amoxicillin-clavulanate with or without clarithromycin (i.v. or p.o.) with respect to clinical success, bacteriological success, and time to fever resolution. In addition, conversion to oral therapy and discharge from the hospital occurred earlier for the patients treated with moxifloxacin.
Rijnders proposes a number of analyses aimed at elucidating the reasons for the superior outcomes observed in moxifloxacin-treated patients. However, the proposed analyses do not reflect prospectively defined endpoints of this study and the numbers of patients available in certain stratifications are small, thus potentially introducing bias and confounding the interpretation of the results. The variables Rijnders proposes to evaluate (e.g., activity against atypical pathogens or effectiveness against CAP in the 10 patients treated in the ICU) certainly warrant investigation but would be best examined in further clinical studies prospectively designed to capture relevant data. We also note that moxifloxacin i.v./p.o. efficacy in patients with severe CAP and CAP due to atypical infections has been analyzed and reported (H. Lode, S. Choudhri, D. Haverstock, P. Jackson, and D. Church, Abstr. 22nd Int. Symp. Intensive Care Emerg. Med., abstr. P88, 2002; S. Larsen, S. Choudhri, D. Haverstock, P. Jackson, and D. Church, Abstr. 41st Intersci. Conf. Antimicrob. Agents Chemother., abstr. 865, 2001) on the basis of a combined analysis of the data generated in our study and a second moxifloxacin i.v./p.o. registration study.
Finally, Rijnders notes that patients who had failed prior fluoroquinolone therapy were excluded from this study. As is routine, patients who had failed prior treatment with the comparator regimen (ß-lactam-ß-lactamase inhibitor combination) were also excluded. Thus, both treatments might have benefited from exclusion of patients at high risk for failure. Rijnders cites two recent publications that suggest that prior treatment with older fluoroquinolones (levofloxacin, ofloxacin, or ciprofloxacin) is a risk factor for development of fluoroquinolone-resistant Streptococcus pneumoniae infection (1, 3). As reflected in recent CAP treatment guidelines from the American Thoracic Society, selection of the most potent fluoroquinolone, with moxifloxacin the most potent (lowest MIC), may be advisable to avoid emergence of fluoroquinolone resistance among S. pneumoniae and maintain the efficacy of this valuable antimicrobial class (4).1rs$\(, http://www.100md.com
REFERENCES1rs$\(, http://www.100md.com
Davidson, R., R. Cavalcanti, J. L. Brunton, D. J. Bast, J. C. de Azavedo, P. Kibsey, C. Fleming, and D. E. Low. 2002. Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N. Engl. J. Med. 346: 747-750.
Finch, R., D. Schürmann, O. Collins, R. Kubin, J. McGivern, H. Bobbaers, J. L. Izquierdo, P. Nikolaides, F. Ogundare, R. Raz, P. Zuck, and G. Höffken. 2002. Randomized controlled trial of sequential intravenous (i.v.) and oral moxifloxacin compared with sequential i.v. and oral co-amoxiclav with or without clarithromycin in patients with community-acquired pneumonia re-quiring initial parenteral treatment. Antimicrob. Agents Chemother. 46: 1746-1754.m(@p1cd, http://www.100md.com
Ho, P. L., W. S. Tse, K. W. Tsang, T. K. Kwok, T. K. Ng, V. C. Cheng, and R. M. Chan. 2001. Risk factors for acquisition of levofloxacin-resistant Streptococcus pneumoniae: a case-control study. Clin. Infect. Dis. 32: 701-707.m(@p1cd, http://www.100md.com
Niederman, M., L. A. Mandell, A. Anzueto, J. B. Bass, W. A. Broughton, G. D. Campell, N. Dean, T. File, M. J. Fine, P. A. Gross, F. Martinez, T. Marrie, J. F. Plouffe, J. Ramirez, G. A. Sarosi, A. Torres, R. Wilson, and V. L. Yu. 2001. Guidelines for the management of adults with community-acquired pneumonia. Am. J. Respir. Crit. Care Med. 163: 1730-1754.
I read with great interest the moxifloxacin versus co-amoxiclav study in the June issue of Antimicrobial Agents and Chemotherapy (2). It is one of the very rare randomized controlled trials on the treatment of community-acquired pneumonia (CAP) that included a significant amount of severely ill patients and pretreated patients and that showed superiority in an intent-to-treat, as well as in an on-treatment, analysis.+, http://www.100md.com
However, it remains unclear if the superiority of moxifloxacin is a consequence of better coverage of the so called "atypical agents," the increased effectiveness in patients with penicillin-resistant pneumococci, the choice of treatment in the control group, or any other reason. A further analysis of the data might therefore be instructive. It would be interesting to know if the difference in outcome between the two study groups is equally, not, or possibly more apparent in patients pretreated and those not pretreated with antibiotics? Is the difference in outcome between the two study groups clearer in those patients in whom any etiologic agent was demonstrated than in those in whom no agent was found?
Very few CAP studies include a significant number of severely ill patients, and therefore, very little evidence from randomized controlled trials is available to guide the management of patients treated in intensive care units (ICUs). Possibly, the moxifloxacin study might give valuable information. Therefore, it would be interesting to know how many of the patients studied were treated in the ICU and how many of them were ventilated during hospitalization. Was the difference in outcome the same in this subgroup of critically ill CAP patients?5h}{&q, 百拇医药
Finally, it is important to remember that although 36% of the patients included in the trial were pretreated with antibiotics (as is the case for "real-life" hospitalized CAP patients), patients pretreated with a fluoroquinolone were excluded and therefore no conclusions about the effectiveness of moxifloxacin in this setting can be drawn. Avoidance of fluoroquinolones as the treatment of choice in this setting may be important (1, 3).
REFERENCES.x?@^, http://www.100md.com
Davidson, R., R. Cavalcanti, J. L. Brunton, D. J. Bast, J. C. de Azavedo, P. Kibsey, C. Fleming, and D. E. Low. 2002. Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N. Engl. J. Med. 346:747-750..x?@^, http://www.100md.com
Finch, R., D. Schürmann, O. Collins, R. Kubin, J. McGivern, H. Bobbaers, J. L. Izquierdo, P. Nikolaides, F. Ogundare, R. Raz, P. Zuck, and G. Höffken. 2002. Randomized controlled trial of sequential intravenous (i.v.) and oral moxifloxacin compared with sequential i.v. and oral co-amoxiclav with or without clarithromycin in patients with community-acquired pneumonia requiring initial parenteral treatment. Antimicrob. Agents Chemother. 46:1746-1754..x?@^, http://www.100md.com
Ho, P. L., W. S. Tse, K. W. Tsang, T. K. Kwok, T. K. Ng, V. C. Cheng, and R. M. Chan. 2001. Risk factors for acquisition of levofloxacin-resistant Streptococcus pneumoniae: a case-control study. Clin. Infect. Dis. 32:701-707..x?@^, http://www.100md.com
Authors' Reply.x?@^, http://www.100md.com
LETTER.x?@^, http://www.100md.com
B. J. A. Rijnders raises several interesting points regarding the CAP study we reported recently (2). This CAP study demonstrated significant superiority of intravenous-to-oral (i.v./p.o.) moxifloxacin monotherapy to i.v./p.o. amoxicillin-clavulanate with or without clarithromycin (i.v. or p.o.) with respect to clinical success, bacteriological success, and time to fever resolution. In addition, conversion to oral therapy and discharge from the hospital occurred earlier for the patients treated with moxifloxacin.
Rijnders proposes a number of analyses aimed at elucidating the reasons for the superior outcomes observed in moxifloxacin-treated patients. However, the proposed analyses do not reflect prospectively defined endpoints of this study and the numbers of patients available in certain stratifications are small, thus potentially introducing bias and confounding the interpretation of the results. The variables Rijnders proposes to evaluate (e.g., activity against atypical pathogens or effectiveness against CAP in the 10 patients treated in the ICU) certainly warrant investigation but would be best examined in further clinical studies prospectively designed to capture relevant data. We also note that moxifloxacin i.v./p.o. efficacy in patients with severe CAP and CAP due to atypical infections has been analyzed and reported (H. Lode, S. Choudhri, D. Haverstock, P. Jackson, and D. Church, Abstr. 22nd Int. Symp. Intensive Care Emerg. Med., abstr. P88, 2002; S. Larsen, S. Choudhri, D. Haverstock, P. Jackson, and D. Church, Abstr. 41st Intersci. Conf. Antimicrob. Agents Chemother., abstr. 865, 2001) on the basis of a combined analysis of the data generated in our study and a second moxifloxacin i.v./p.o. registration study.
Finally, Rijnders notes that patients who had failed prior fluoroquinolone therapy were excluded from this study. As is routine, patients who had failed prior treatment with the comparator regimen (ß-lactam-ß-lactamase inhibitor combination) were also excluded. Thus, both treatments might have benefited from exclusion of patients at high risk for failure. Rijnders cites two recent publications that suggest that prior treatment with older fluoroquinolones (levofloxacin, ofloxacin, or ciprofloxacin) is a risk factor for development of fluoroquinolone-resistant Streptococcus pneumoniae infection (1, 3). As reflected in recent CAP treatment guidelines from the American Thoracic Society, selection of the most potent fluoroquinolone, with moxifloxacin the most potent (lowest MIC), may be advisable to avoid emergence of fluoroquinolone resistance among S. pneumoniae and maintain the efficacy of this valuable antimicrobial class (4).1rs$\(, http://www.100md.com
REFERENCES1rs$\(, http://www.100md.com
Davidson, R., R. Cavalcanti, J. L. Brunton, D. J. Bast, J. C. de Azavedo, P. Kibsey, C. Fleming, and D. E. Low. 2002. Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N. Engl. J. Med. 346: 747-750.
Finch, R., D. Schürmann, O. Collins, R. Kubin, J. McGivern, H. Bobbaers, J. L. Izquierdo, P. Nikolaides, F. Ogundare, R. Raz, P. Zuck, and G. Höffken. 2002. Randomized controlled trial of sequential intravenous (i.v.) and oral moxifloxacin compared with sequential i.v. and oral co-amoxiclav with or without clarithromycin in patients with community-acquired pneumonia re-quiring initial parenteral treatment. Antimicrob. Agents Chemother. 46: 1746-1754.m(@p1cd, http://www.100md.com
Ho, P. L., W. S. Tse, K. W. Tsang, T. K. Kwok, T. K. Ng, V. C. Cheng, and R. M. Chan. 2001. Risk factors for acquisition of levofloxacin-resistant Streptococcus pneumoniae: a case-control study. Clin. Infect. Dis. 32: 701-707.m(@p1cd, http://www.100md.com
Niederman, M., L. A. Mandell, A. Anzueto, J. B. Bass, W. A. Broughton, G. D. Campell, N. Dean, T. File, M. J. Fine, P. A. Gross, F. Martinez, T. Marrie, J. F. Plouffe, J. Ramirez, G. A. Sarosi, A. Torres, R. Wilson, and V. L. Yu. 2001. Guidelines for the management of adults with community-acquired pneumonia. Am. J. Respir. Crit. Care Med. 163: 1730-1754.