Treatment of Anaerobic Pulmonary Infections* Carbenicillin Compared to Clindamycin and Gentamicin Haragopal Thadepalli, M.D.;oO Albert H. Niden, M.D., F.C.C.P.;tand long T. Hoong, M.D.*
Twenty-three patients with aoaeroblc infections of the IUDI were treated with either two antibiotics, cUndamycin and gentamicin (11 patients) or with a single antibiotic, carbeniclDln (12 patients). Cultures were obtained prior to therapy, either by transtracheal needle aspiration (17 patients) or thoracocentesis (six patients). Anaerobic bacteria were foulld In aIL Fifteen patients had aerobic and facultative bacteria in addition. The anaerobic isolates were peptostreptococcl (12), peptococci (12), Bacteroides organisms (eight), clostridia (three), actinomycetes (two), eubacterla (one), and fusobacteria (one). Aerobes in-
eluded streptococci (nine), enterococci (seven), Neisseria organisms (two), KlebsieUa organisms (one), Citrobacter organisms (one), Pseudomonas organisms (one), Mycobacterium tubnculosis (two), and Nocardia (one). The two patients with pulmonary tuberculosis with anaerobic and superinfection received antituberculosis chemotherapy in addition. Therapeutic response was CODsidered exceUent in both groups. ThIs suggests that car· benlcDlln may be used as a single antibiotic in the treat· ment of anaerobic and mixed infections of the lung.
Anaerobic infections of the lung are often associated with aerobic bacteria. 1 Improved anaerobic techniques2 and frequent use of transtracheal aspiration3 for diagnosis has increased the recognition of anaerobic pulmonary infections. The general consensus is that penicillin G is the drug of . choice for anaerobic pulmonary infections! even if associated with aerobic bacteria; however, controlled prospective studies with microbiologic data in comparison to the therapeutic effect of modem antibiotics, such as clindamycin or carbenicillin, are not available. It is unclear if antipolymicrobial therapy,is required to "cover all" aerobic and anaerobic bacteria found in this setting. Combined therapy with clindamycin and gentamicin is becoming popular to treat such mixed infections. 5•6 Therapy with carbenicillin, commonly. used for infections with Pseudomonas, was reported to be effective against anaerobes in vitro. 7 To evaluate the effect of therapy with carbenicillin in the treatment of anaerobic pulmonary infections, a comparison was made to combined therapy with clindamycin and gentamicin.
MATERIALS AND METHODS
Patients Twenty-one men and two women (mean age, 27 years) who were diagnosed to have anaerobic pleuropulmonary infections were treated with either (1) carbenicillin (6 gm intravenously every six hours), or (2) with clindamycin (600 mg intravenously every six hours) and gentamicin (80 mg intravenously every 12 hours). The history, physical signs, clinical symptoms, and roentgenographic Bndings of the chest were the bases of the clinical diagnosis (Table 1). Cultures were obtained by transtracheal aspiration (17 patients) or thoracocentesis (six patients) prior to the administration of protocol antibiotics. Both carbenicillin and clindamycin dosages were later changed to the oral route when the patient's clinical status improved, and gentamicin therapy was then discontinued.
Laboratory Techniques Anaerobic cultures were perfonned according to techniques described in the Anaerobe Laboratory Manual. 2 Aerobes were identified by conventional methods. In vitro testing of anaerobes was perfonned by the agar-dilution Table l-CUnica' Dia«noai. and Di.,ribution of Patien,. by Antibiotic Group
°From the Divisions of Infectious Diseases and Pulmonary Medicine, Department of Internal Medicine, Martin Luther King, Jr. General Hospital, Charles R. Drew Postgraduate Medical School, and University of Southern California School of Medicine, Los Angeles. 00 Assistant Professor of Medicine. tProfessor of Medicine. tFellow in Infectious Diseases. Manuscript received August 11; revision accepted December 29. Reprint requests: Dr. rhadevalli, 12021 South Wilmington,
Diagnosis
Carbenicillin
Lung abscess Necrotizing pneumonia Empyema Aspiration pneumonia Total No. of patients
5 3 2 2 12
CHEST, 69: 6, JUNE, 1976
TREATMENT OF ANAEROBIC PULMONARY INFECTIONS 743
Los Angeles 90059
Total Clindamycin No. of and Gentamicin Patients 1
2 4 4 11
6 5 6 6 23
technique 7 in a glove box. 8 Serum levels of carbenicillin were detennined by a bioassay microtitimetric method against a known susceptible strain of Escherichia coli.
Table 3--.4ndbiode Sueepdbility of Anaerobe.
Follow-Up
Isolates (No.)
Minimal Inhibitory Concentration, pg/ml A
Serial roentgenograms of the chest were obtained at weekly intervals or more often when indicated. Other laboratory tests monitoring the hematologic, hepatic, and renal status of the patient were perfonned at weekly intervals and repeated as often as indicated. REsULTS
Bacteriologic Findings Anaerobes were found in pure culture in the specimens obtained from about one-third (eight) of the patients. The rest (15 patients) had aerobic and facultative bacteria in addition. There were no significant differences e:ther in the total numbers of aerobic (14 and 10) or anaerobic (21 and 18) isolates recovered between the two antibiotic groups. Bacteroides organisms were found in both groups (three and four patients per group). Bacteroides fragilis, subspecies fragilis, was cultured from the transtracheal aspirate of one patient who had aspiration pneumonia. The aerobic and anaerobic bacteria are listed in Table 2.
Anaerobic Bacteria Peptostreptococci (12 isolates) and peptococci (12 isolates) predominated in both antibiotic groups, "followed by Bacteroides (eight isolates) and clostridia (three isolates). Both isolates of Actinomyces were recovered from the carbenicillin group. FusoTable 2-.4erobic and Anaerobic .lao'alea Isolates
Carbenicillin
Aerobic isolates Streptococcus Enterococcus Neisseria Klebsiella Citrobacter Pseudomonas Mycobacterium tuberculosis Nocardia Total aerobic isolates
1 1* 0 14
Anaerobic isolates Peptostreptococcus Peptococcus Bacteroides Fusobacterium Eubacterium Clostridium Actinomyces Total anaerobic isolates
7 5 4 1 0 2 2 21
5 5 1 0 1
*Received antituberculosis therapy.
744 THADEPALLI, NIDEN, HUANG
Clindamycin and Gentamicin 4
2 1 1 0 0 1* 1 10 5 7 4 0 1
1 0 18
Carbenicillin"
Peptostreptococcus (12) PeptococcUB (12) Bacteroides (8) Fusobacterium .(1) Eubacterium (1) Clostridium (3) Actinomyces (2)
Twenty-three patients with aoaeroblc infections of the IUDI were treated with either two antibiotics, cUndamycin and gentamicin (11 patients) or with a single antibiotic, carbeniclDln (12 patients). Cultures were obtained prior to therapy, either by transtracheal needle aspiration (17 patients) or thoracocentesis (six patients). Anaerobic bacteria were foulld In aIL Fifteen patients had aerobic and facultative bacteria in addition. The anaerobic isolates were peptostreptococcl (12), peptococci (12), Bacteroides organisms (eight), clostridia (three), actinomycetes (two), eubacterla (one), and fusobacteria (one). Aerobes in-
eluded streptococci (nine), enterococci (seven), Neisseria organisms (two), KlebsieUa organisms (one), Citrobacter organisms (one), Pseudomonas organisms (one), Mycobacterium tubnculosis (two), and Nocardia (one). The two patients with pulmonary tuberculosis with anaerobic and superinfection received antituberculosis chemotherapy in addition. Therapeutic response was CODsidered exceUent in both groups. ThIs suggests that car· benlcDlln may be used as a single antibiotic in the treat· ment of anaerobic and mixed infections of the lung.
Anaerobic infections of the lung are often associated with aerobic bacteria. 1 Improved anaerobic techniques2 and frequent use of transtracheal aspiration3 for diagnosis has increased the recognition of anaerobic pulmonary infections. The general consensus is that penicillin G is the drug of . choice for anaerobic pulmonary infections! even if associated with aerobic bacteria; however, controlled prospective studies with microbiologic data in comparison to the therapeutic effect of modem antibiotics, such as clindamycin or carbenicillin, are not available. It is unclear if antipolymicrobial therapy,is required to "cover all" aerobic and anaerobic bacteria found in this setting. Combined therapy with clindamycin and gentamicin is becoming popular to treat such mixed infections. 5•6 Therapy with carbenicillin, commonly. used for infections with Pseudomonas, was reported to be effective against anaerobes in vitro. 7 To evaluate the effect of therapy with carbenicillin in the treatment of anaerobic pulmonary infections, a comparison was made to combined therapy with clindamycin and gentamicin.
MATERIALS AND METHODS
Patients Twenty-one men and two women (mean age, 27 years) who were diagnosed to have anaerobic pleuropulmonary infections were treated with either (1) carbenicillin (6 gm intravenously every six hours), or (2) with clindamycin (600 mg intravenously every six hours) and gentamicin (80 mg intravenously every 12 hours). The history, physical signs, clinical symptoms, and roentgenographic Bndings of the chest were the bases of the clinical diagnosis (Table 1). Cultures were obtained by transtracheal aspiration (17 patients) or thoracocentesis (six patients) prior to the administration of protocol antibiotics. Both carbenicillin and clindamycin dosages were later changed to the oral route when the patient's clinical status improved, and gentamicin therapy was then discontinued.
Laboratory Techniques Anaerobic cultures were perfonned according to techniques described in the Anaerobe Laboratory Manual. 2 Aerobes were identified by conventional methods. In vitro testing of anaerobes was perfonned by the agar-dilution Table l-CUnica' Dia«noai. and Di.,ribution of Patien,. by Antibiotic Group
°From the Divisions of Infectious Diseases and Pulmonary Medicine, Department of Internal Medicine, Martin Luther King, Jr. General Hospital, Charles R. Drew Postgraduate Medical School, and University of Southern California School of Medicine, Los Angeles. 00 Assistant Professor of Medicine. tProfessor of Medicine. tFellow in Infectious Diseases. Manuscript received August 11; revision accepted December 29. Reprint requests: Dr. rhadevalli, 12021 South Wilmington,
Diagnosis
Carbenicillin
Lung abscess Necrotizing pneumonia Empyema Aspiration pneumonia Total No. of patients
5 3 2 2 12
CHEST, 69: 6, JUNE, 1976
TREATMENT OF ANAEROBIC PULMONARY INFECTIONS 743
Los Angeles 90059
Total Clindamycin No. of and Gentamicin Patients 1
2 4 4 11
6 5 6 6 23
technique 7 in a glove box. 8 Serum levels of carbenicillin were detennined by a bioassay microtitimetric method against a known susceptible strain of Escherichia coli.
Table 3--.4ndbiode Sueepdbility of Anaerobe.
Follow-Up
Isolates (No.)
Minimal Inhibitory Concentration, pg/ml A
Serial roentgenograms of the chest were obtained at weekly intervals or more often when indicated. Other laboratory tests monitoring the hematologic, hepatic, and renal status of the patient were perfonned at weekly intervals and repeated as often as indicated. REsULTS
Bacteriologic Findings Anaerobes were found in pure culture in the specimens obtained from about one-third (eight) of the patients. The rest (15 patients) had aerobic and facultative bacteria in addition. There were no significant differences e:ther in the total numbers of aerobic (14 and 10) or anaerobic (21 and 18) isolates recovered between the two antibiotic groups. Bacteroides organisms were found in both groups (three and four patients per group). Bacteroides fragilis, subspecies fragilis, was cultured from the transtracheal aspirate of one patient who had aspiration pneumonia. The aerobic and anaerobic bacteria are listed in Table 2.
Anaerobic Bacteria Peptostreptococci (12 isolates) and peptococci (12 isolates) predominated in both antibiotic groups, "followed by Bacteroides (eight isolates) and clostridia (three isolates). Both isolates of Actinomyces were recovered from the carbenicillin group. FusoTable 2-.4erobic and Anaerobic .lao'alea Isolates
Carbenicillin
Aerobic isolates Streptococcus Enterococcus Neisseria Klebsiella Citrobacter Pseudomonas Mycobacterium tuberculosis Nocardia Total aerobic isolates
1 1* 0 14
Anaerobic isolates Peptostreptococcus Peptococcus Bacteroides Fusobacterium Eubacterium Clostridium Actinomyces Total anaerobic isolates
7 5 4 1 0 2 2 21
5 5 1 0 1
*Received antituberculosis therapy.
744 THADEPALLI, NIDEN, HUANG
Clindamycin and Gentamicin 4
2 1 1 0 0 1* 1 10 5 7 4 0 1
1 0 18
Carbenicillin"
Peptostreptococcus (12) PeptococcUB (12) Bacteroides (8) Fusobacterium .(1) Eubacterium (1) Clostridium (3) Actinomyces (2)
