å¡ CASE REPORT å¡ Fatal Pneumonia Caused by Corynebacterium Group JK after Treatment of Staphylococcus aureus Pneumonia Yuko Yoshitomi, Shigeru Kohno, Hironobu Koga, Shigefumi Maesaki, Yasuhito Higashiyama, Haruko Matsuda, Kohtarou Mitsutake, Yoshitsugu Miyazaki, Hiroshi Yamada, Kohei Hara, Kazuyuki Sugahara* and Mitsuo Kaku* A 76-year-old man who was admitted to the hospital because of chronic renal insufficiency and chronic hepatitis died of Corynebacterium group JK pneumonia, after showing a slight improvement by treatment of Staphylococcus aureus with sulbactam/cefoperazone and mino cycline. Transtracheal aspiration (TTA) just before his death revealed numerous gram-positive bacilli phagocytized by many neutrophils and more than 108 colony forming units (CFU)/ml of Corynebacterium group JK. A drug susceptibility test showed Corynebacterium group JK was (Internal resistant Medicine to many antibiotics, 31: 930-932, with 1992) the exception of vancomycin and amikacin. Key words: nondiphtheria corynebacteria, transtracheal aspiration, bacterial change
Introduction
of 3 1/min showed hypoxia (Po2 50 Torr) and hypocapnia (Pco2 33.2 Torr). A chest radiograph showed old lesions Nondiphtheria corynebacteria are normal skin flora of pulmonary tuberculosis in the right upper lobe and (1-4) and although respiratory tract infection caused infiltrates in the middle field of the right lung (Fig. 1). by these organisms has recently been reported (5-10), The first transtracheal aspiration (TTA) was per their pathogenicity in respiratory tract infection has not formed. Many neutrophils and phagocytized gram been proven. Corynebacterium group JK in particular positive cocci were observed in a gram stain of the is resistant to many antibiotics and can cause serious specimen (Fig. 2); most were gram-positive cocci, but infection in compromised hosts (1-3, 5-7, ll). This is gram-positive bacilli phagocytized by neutrophils were the first case of Corynebacterium group JK pneumonia also found sparsely distributed. More than 107 CFU/ml in Japan. of Staphylococcus aureus, 106 CFU/ml of Corynebacterium Case Report group JK, and 103 CFU/ml of Pseudomonas aeruginosa were isolated from the specimen. S. aureus was also iso The patient, a 76-year-old man with old pulmonary lated from blood. Following administration of sulbactam/ tuberculosis, developed fever, stridor, and vomiting in cefoperazone 2 g/day and minocycline 200mg/day, the early May 1990 during hospitalization, because of chronic patient's fever abated somewhat and laboratory data However, his condition soon deteriorated, and the tem renal insufficiency and chronic hepatitis. At that time his improved (the WBC 4,200/mm3 and CRP 1.6mg/dl). perature rose to 40°C. The second TTA was performed temperature was 38.5°C. He presented cyanosis and 9 days after the first. A gram stained specimen revealed had moist rales in both lungs. Laboratory data revealed numerous gram-positive bacilli, some of which were a white blood cell (WBC) count of 19,200/mm3 with phagocytized by neutrophils, but there were few gram 35% segmented forms and 33% band forms, C-reactive positive cocci (Fig. 3). More than 108 CFU/ml of Coryne protein (CRP) 19.8 mg/dl, total protein 5.5 g/dl, albumin bacterium group JK, 104 CFU/ml of P. aeruginosa, and 2.7g/dl, GOT 43IU/1, GPT 21IU/1, total bilirubin 103CFU/ml of S. aureus were isolated from the second Arterial blood gas values under nasal oxygen supply 1.4mg/dl, BUN 87.0mg/dl, and the creatinine 3.3mg/dl. TTA. The patient died of respiratory failure on the day From the Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, and *the Department of Clinica Laboratory, Nagasaki University Hospital, Nagasaki Received for publication July 7, 1991; Accepted for publication March 31, 1992 Reprint requests should be addressed to Dr. Yuko Yoshitomi, the Second Department of Internal Medicine, Nagasaki University Schoo Medicine. 7-1, 1-chome Sakamoto, Nagasaki 852, Japan 930
Internal
Medicine
Vol. 31, No. 7 (July
1992)
Corynebacterium
Group JK Pneumonia
Fig. 3. Gram stain of the second TTA (x1,000) showing num erous gram-positive bacilli, which are phagocytized in neutrophils. T able 1. B io ch em ical C haracteristics of C o ry'nebacterium G rou p JK
Fig. 1. A chest radiograph of the first episode of pneu monia. Old lesions of pulmonary tuberculosis in the right upper lobe and infiltrates in the middle field of the right lung can be seen.
G ram stain C ataiase G lucose M altose Sucrose M an nitol X ylo se E sculin U rease N itrate redu ctio n O N PG *
G ram -p ositive rod s
: o-Nitrophenyl-/3-D-galactopyranoside.
Table 2. MICs of Corynebacterium Group JK (/ig/ml)
Fig. 2. Gram stain of the first TTA (x1,000) showing many neutrophils and phagocytized gram-positive cocci. of the second TTA. Corynebacterium group JK was identified by gram stain, catalase, carbohydrate utilization, esculin, urease, nitrate reduction, o-nitrophenyl-/3-D-galactopyranoside (ONPG) (Table 1) (1, 2, ll). The Minitek system (BBL, U.S.A.) and ID test NF-18 (Nissui, Japan) were used for identification (12, 13). The organism grew well on agar supplemented with Tween 80.(MICs) of anti Minimal inhibitory concentrations biotics were determined by the microbroth dilution method. The MIC of vancomycin was 1.56 ^g/ml, amika cin 2.5 -|Ug/ml, erythromycin 5.0 /ig/ml, and the MICs of Internal
Medicine
Vol. 31, No. 7 (July
1992)
penicillin G >25 cefuzonam >25 ampicillin > 25 gentamicin > 25 cloxacillin >25 amikacin 2. 5 imipenem/cilastatin 25 erythromycin 5. 0 cefaclor >25 clindamycin > 25 cefazolin > 25 minocycline 25 cefotiam >25 ofloxacin > 25 cefmetazole > 25 vancomycin 1. 56 other antibiotics were more than 25 /ig/ml (Table 2). Discussion Infections caused by nondiphtheria corynebacteria include lymphadenitis, pneumonia, pharyngitis, and wound infections due to C. pseudotuberculosis, C. equi, C. ulcerans, and C. bovis, which are pathogens of animals (1, 2, 14); and as sepsis, endocarditis, and respiratory tract infections due to C. pseudodiphtheriticum, Coryne bacterium group JK, and C. xerosis, which are part of the normal flora of the skin or mucous membrane have been reported (1-3, 5-ll, 15-17). Corynebacterium group JK can cause infection in 931
Yoshitomi et al immunocompromised hosts, and particularly in neutro penic patients (3, 5, 7, ll). Among the infections, sepsis is common, and pneumonia in immunocompromised hosts, or endocarditis in prosthetic valve patients have also been reported (1-3, 5-7, ll, 17). Pathologic findings of pneumonia due to Corynebacterium group JK are characterized by necrosis (5). Bacteriological study shows this organism to be resistant to many antibiotics We not perform an autopsy, but we anddid susceptible to only vancomycin (3,deduced 5-7, ll, 17). that the patient died of Corynebacterium group JK pneumonia from the bacteriological results just before his death. We attributed the first episode of pneumonia to S. aureus, as it was the main isolate from the first TTA specimen and blood. A few phagocytized gram positive bacilli were also seen in a gram stained specimen of the first TTA, and 106CFU/ml of Corynebacterium group JK were isolated from that specimen. Corynebac terium group JK was not isolated from the blood, but it has been reported that the isolation of this organism from blood culture usually takes several days or weeks (5, 17). Therefore, the first episode of pneumonia might have been caused by mixed infection of S. aureus and Corynebacterium group JK. We assumed the principal cause to be S. aureus because administration of sulbactam/ cefoperazone and minocycline, both of which have anti microbial activity against S. aureus, brought about an improvement and decreased S. aureus in the second TTA. But soon his condition deteriorated and he died of respiratory failure. The second TTA revealed insig nificant amounts of S. aureus (103 CFU/ml) compared with the large amounts of Corynebacterium group JK, which we assumed to be the pathogen of the terminal Pneumonia by this organism has been reported pneumonia.caused We concluded that the patient died of in one patient withgroup chronic dis Corynebacterium JK obstructive pneumonia pulmonary following treat ease but without impaired immunity (6). In the present ment for S. aureus pneumonia. patient, the neutrophil function or other immunity was not examined, but he was in a condition of malnutrition and showed chronic renal insufficiency and chronic hepatitis. In North America, infections such as sepsis, endo carditis, and pneumonia caused by Corynebacterium group JK in immunocompromised hosts have been reported (1-3, 5-7, ll). In Japan, however, this is the first report of pneumonia caused by Corynebacterium groupcolonization JK, as far asofwe ascertain from previous Skin Corynebacterium group JKreports. in Japanese who have stayed in the United States has been reported (18). Uncommon reports may be due to the mistaking of isolated organisms for contamination from skin flora, and the difficulty of its isolation and identi-
932
fication because of its poor growth and inactive bio chemical reaction (3. ll-13, 17). Thus Corynebacterium group JK should be recognized as a potential pathogen in immunocompromised hosts; furthermore, it is noteworthy that this organism is resist ant to many antibiotics. References 1) Coyle MB, Hollis DG, Groman NB. Manual of Clinical Micro biology, 4th ed , American Society for Microbiology, Washington, D.C., 1985, p. 193. 2) Lipsky BA, Goldberger AC, Tompkins LS, Plorde JJ. Infections caused by nondiphtheria corynebacteria. Rev Infect Dis 4: 1220, 1982. 3) Gill VJ, Manning C, Lamson M, Woltering P, Pizzo PA. Anti biotic-resistant group JK bacteria in hospitals. J Clin Microbiol 13: 472, 1981. 4) Soriano F, Rodrigues-tudela JL, Fernandez-roblas R, Aguado JM, Santamaria M. Skin colonization by Corynebacterium group D2 and JK in hospitalized patients. J Clin Microbiol 26: 1878, 1988. 5) Waters BL. Pathology culture-proven JK corynebacterium pneumonia. Am J Clin Pathol 91: 616, 1989. 6) McNaughton RD, Villanueva RR, Donnelly R, Freedman J, Nawrot R. Cavitating pneumonia caused by Corynebacterium group JK. J Clin Microbiol 26: 2216, 1988. 7) Guarino MJ, Qazi R, Woll JE, Rubins J. Septicemia, rash, and pulmonary infiltrates secondary to Corynebacterium group JK infection. Am J Med 82: 132, 1987. 8) Yoshitomi Y, Koga H, Kohno S, Hara K, et al. Four cases of respiratory tract infections caused by Corynebacterium pseudo diphtheriticum. J Jpn Assoc Infect Dis 66: 87, 1992 (in Japanese). 9) Rikitomi N, Nagatake T, Matsumoto K, Watanabe K, Mbaki N. Lower respiratory tract infections due to non-diphtheria Corynebacteria in 8 patients with underlying lung diseases. Tohoku J Exp Med 153: 313, 1987. 10) Donaghy M, Cohen J. Pulmonary infection with Corynebacterium hofmannii complicating systemic lupus erythematosus. J Infect Dis 147: 962, 1983. ll) Riley PS, Hollis DG, Utter GB, Weaver RE, Baker CN. Charac terization and identification of 95 diphtheroid (group JK) cultures isolated from clinical specimens. J Clin Microbiol 9: 418, 1979. 12) Slifkin M, Gil GM, Engwall C. Rapid identification of group JK and other corynebacteria with the Minitek system. J Clin Microbiol 24: 177, 1986. 13) Sako H, Tanaka M, Watanabe S, Oku K, Hishimoto T, Funabashi N. Application of ID test NF-18 to identification of the genus Corynebacterium. Media Circle 35: 191, 1990 (in Japanese). 14) Egawa T, Hara H, Kawase I, et al. Human pulmonary infection with Corynebacterium equi. Eur Respir J 3: 240, 1990. 15) Johnson WD, Cobbs CG, Arditi LI, Kaye D. Diphtheroid endo carditis after infection of a prosthetic heart valve. JAMA 203: 919, 1968. 16) Mizuno H, Wada I, Miyaji T. Acute suppurative otitis media with Corynebacterium pseudodiphtheriticum. Rinsho-to-Biseibutsu 15: 380, 1988 (in Japanese). 17) Scoy REV, Cohen SN, Geraci JE, Washington JA. Coryneform bacterial endocarditis. Mayo Clin Proc 52: 216, 1977. 18) Nishijima S, McGinley KJ, Leyden JJ. Group JK (Corynebacte rium jeikeium sp. nov.) isolated from Japanese skin flora. Jpn J Dermatol 99: 1121, 1989 (in Japanese).
Internal
Medicine
Vol. 31, No. 7 (July
1992)
Introduction
of 3 1/min showed hypoxia (Po2 50 Torr) and hypocapnia (Pco2 33.2 Torr). A chest radiograph showed old lesions Nondiphtheria corynebacteria are normal skin flora of pulmonary tuberculosis in the right upper lobe and (1-4) and although respiratory tract infection caused infiltrates in the middle field of the right lung (Fig. 1). by these organisms has recently been reported (5-10), The first transtracheal aspiration (TTA) was per their pathogenicity in respiratory tract infection has not formed. Many neutrophils and phagocytized gram been proven. Corynebacterium group JK in particular positive cocci were observed in a gram stain of the is resistant to many antibiotics and can cause serious specimen (Fig. 2); most were gram-positive cocci, but infection in compromised hosts (1-3, 5-7, ll). This is gram-positive bacilli phagocytized by neutrophils were the first case of Corynebacterium group JK pneumonia also found sparsely distributed. More than 107 CFU/ml in Japan. of Staphylococcus aureus, 106 CFU/ml of Corynebacterium Case Report group JK, and 103 CFU/ml of Pseudomonas aeruginosa were isolated from the specimen. S. aureus was also iso The patient, a 76-year-old man with old pulmonary lated from blood. Following administration of sulbactam/ tuberculosis, developed fever, stridor, and vomiting in cefoperazone 2 g/day and minocycline 200mg/day, the early May 1990 during hospitalization, because of chronic patient's fever abated somewhat and laboratory data However, his condition soon deteriorated, and the tem renal insufficiency and chronic hepatitis. At that time his improved (the WBC 4,200/mm3 and CRP 1.6mg/dl). perature rose to 40°C. The second TTA was performed temperature was 38.5°C. He presented cyanosis and 9 days after the first. A gram stained specimen revealed had moist rales in both lungs. Laboratory data revealed numerous gram-positive bacilli, some of which were a white blood cell (WBC) count of 19,200/mm3 with phagocytized by neutrophils, but there were few gram 35% segmented forms and 33% band forms, C-reactive positive cocci (Fig. 3). More than 108 CFU/ml of Coryne protein (CRP) 19.8 mg/dl, total protein 5.5 g/dl, albumin bacterium group JK, 104 CFU/ml of P. aeruginosa, and 2.7g/dl, GOT 43IU/1, GPT 21IU/1, total bilirubin 103CFU/ml of S. aureus were isolated from the second Arterial blood gas values under nasal oxygen supply 1.4mg/dl, BUN 87.0mg/dl, and the creatinine 3.3mg/dl. TTA. The patient died of respiratory failure on the day From the Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, and *the Department of Clinica Laboratory, Nagasaki University Hospital, Nagasaki Received for publication July 7, 1991; Accepted for publication March 31, 1992 Reprint requests should be addressed to Dr. Yuko Yoshitomi, the Second Department of Internal Medicine, Nagasaki University Schoo Medicine. 7-1, 1-chome Sakamoto, Nagasaki 852, Japan 930
Internal
Medicine
Vol. 31, No. 7 (July
1992)
Corynebacterium
Group JK Pneumonia
Fig. 3. Gram stain of the second TTA (x1,000) showing num erous gram-positive bacilli, which are phagocytized in neutrophils. T able 1. B io ch em ical C haracteristics of C o ry'nebacterium G rou p JK
Fig. 1. A chest radiograph of the first episode of pneu monia. Old lesions of pulmonary tuberculosis in the right upper lobe and infiltrates in the middle field of the right lung can be seen.
G ram stain C ataiase G lucose M altose Sucrose M an nitol X ylo se E sculin U rease N itrate redu ctio n O N PG *
G ram -p ositive rod s
: o-Nitrophenyl-/3-D-galactopyranoside.
Table 2. MICs of Corynebacterium Group JK (/ig/ml)
Fig. 2. Gram stain of the first TTA (x1,000) showing many neutrophils and phagocytized gram-positive cocci. of the second TTA. Corynebacterium group JK was identified by gram stain, catalase, carbohydrate utilization, esculin, urease, nitrate reduction, o-nitrophenyl-/3-D-galactopyranoside (ONPG) (Table 1) (1, 2, ll). The Minitek system (BBL, U.S.A.) and ID test NF-18 (Nissui, Japan) were used for identification (12, 13). The organism grew well on agar supplemented with Tween 80.(MICs) of anti Minimal inhibitory concentrations biotics were determined by the microbroth dilution method. The MIC of vancomycin was 1.56 ^g/ml, amika cin 2.5 -|Ug/ml, erythromycin 5.0 /ig/ml, and the MICs of Internal
Medicine
Vol. 31, No. 7 (July
1992)
penicillin G >25 cefuzonam >25 ampicillin > 25 gentamicin > 25 cloxacillin >25 amikacin 2. 5 imipenem/cilastatin 25 erythromycin 5. 0 cefaclor >25 clindamycin > 25 cefazolin > 25 minocycline 25 cefotiam >25 ofloxacin > 25 cefmetazole > 25 vancomycin 1. 56 other antibiotics were more than 25 /ig/ml (Table 2). Discussion Infections caused by nondiphtheria corynebacteria include lymphadenitis, pneumonia, pharyngitis, and wound infections due to C. pseudotuberculosis, C. equi, C. ulcerans, and C. bovis, which are pathogens of animals (1, 2, 14); and as sepsis, endocarditis, and respiratory tract infections due to C. pseudodiphtheriticum, Coryne bacterium group JK, and C. xerosis, which are part of the normal flora of the skin or mucous membrane have been reported (1-3, 5-ll, 15-17). Corynebacterium group JK can cause infection in 931
Yoshitomi et al immunocompromised hosts, and particularly in neutro penic patients (3, 5, 7, ll). Among the infections, sepsis is common, and pneumonia in immunocompromised hosts, or endocarditis in prosthetic valve patients have also been reported (1-3, 5-7, ll, 17). Pathologic findings of pneumonia due to Corynebacterium group JK are characterized by necrosis (5). Bacteriological study shows this organism to be resistant to many antibiotics We not perform an autopsy, but we anddid susceptible to only vancomycin (3,deduced 5-7, ll, 17). that the patient died of Corynebacterium group JK pneumonia from the bacteriological results just before his death. We attributed the first episode of pneumonia to S. aureus, as it was the main isolate from the first TTA specimen and blood. A few phagocytized gram positive bacilli were also seen in a gram stained specimen of the first TTA, and 106CFU/ml of Corynebacterium group JK were isolated from that specimen. Corynebac terium group JK was not isolated from the blood, but it has been reported that the isolation of this organism from blood culture usually takes several days or weeks (5, 17). Therefore, the first episode of pneumonia might have been caused by mixed infection of S. aureus and Corynebacterium group JK. We assumed the principal cause to be S. aureus because administration of sulbactam/ cefoperazone and minocycline, both of which have anti microbial activity against S. aureus, brought about an improvement and decreased S. aureus in the second TTA. But soon his condition deteriorated and he died of respiratory failure. The second TTA revealed insig nificant amounts of S. aureus (103 CFU/ml) compared with the large amounts of Corynebacterium group JK, which we assumed to be the pathogen of the terminal Pneumonia by this organism has been reported pneumonia.caused We concluded that the patient died of in one patient withgroup chronic dis Corynebacterium JK obstructive pneumonia pulmonary following treat ease but without impaired immunity (6). In the present ment for S. aureus pneumonia. patient, the neutrophil function or other immunity was not examined, but he was in a condition of malnutrition and showed chronic renal insufficiency and chronic hepatitis. In North America, infections such as sepsis, endo carditis, and pneumonia caused by Corynebacterium group JK in immunocompromised hosts have been reported (1-3, 5-7, ll). In Japan, however, this is the first report of pneumonia caused by Corynebacterium groupcolonization JK, as far asofwe ascertain from previous Skin Corynebacterium group JKreports. in Japanese who have stayed in the United States has been reported (18). Uncommon reports may be due to the mistaking of isolated organisms for contamination from skin flora, and the difficulty of its isolation and identi-
932
fication because of its poor growth and inactive bio chemical reaction (3. ll-13, 17). Thus Corynebacterium group JK should be recognized as a potential pathogen in immunocompromised hosts; furthermore, it is noteworthy that this organism is resist ant to many antibiotics. References 1) Coyle MB, Hollis DG, Groman NB. Manual of Clinical Micro biology, 4th ed , American Society for Microbiology, Washington, D.C., 1985, p. 193. 2) Lipsky BA, Goldberger AC, Tompkins LS, Plorde JJ. Infections caused by nondiphtheria corynebacteria. Rev Infect Dis 4: 1220, 1982. 3) Gill VJ, Manning C, Lamson M, Woltering P, Pizzo PA. Anti biotic-resistant group JK bacteria in hospitals. J Clin Microbiol 13: 472, 1981. 4) Soriano F, Rodrigues-tudela JL, Fernandez-roblas R, Aguado JM, Santamaria M. Skin colonization by Corynebacterium group D2 and JK in hospitalized patients. J Clin Microbiol 26: 1878, 1988. 5) Waters BL. Pathology culture-proven JK corynebacterium pneumonia. Am J Clin Pathol 91: 616, 1989. 6) McNaughton RD, Villanueva RR, Donnelly R, Freedman J, Nawrot R. Cavitating pneumonia caused by Corynebacterium group JK. J Clin Microbiol 26: 2216, 1988. 7) Guarino MJ, Qazi R, Woll JE, Rubins J. Septicemia, rash, and pulmonary infiltrates secondary to Corynebacterium group JK infection. Am J Med 82: 132, 1987. 8) Yoshitomi Y, Koga H, Kohno S, Hara K, et al. Four cases of respiratory tract infections caused by Corynebacterium pseudo diphtheriticum. J Jpn Assoc Infect Dis 66: 87, 1992 (in Japanese). 9) Rikitomi N, Nagatake T, Matsumoto K, Watanabe K, Mbaki N. Lower respiratory tract infections due to non-diphtheria Corynebacteria in 8 patients with underlying lung diseases. Tohoku J Exp Med 153: 313, 1987. 10) Donaghy M, Cohen J. Pulmonary infection with Corynebacterium hofmannii complicating systemic lupus erythematosus. J Infect Dis 147: 962, 1983. ll) Riley PS, Hollis DG, Utter GB, Weaver RE, Baker CN. Charac terization and identification of 95 diphtheroid (group JK) cultures isolated from clinical specimens. J Clin Microbiol 9: 418, 1979. 12) Slifkin M, Gil GM, Engwall C. Rapid identification of group JK and other corynebacteria with the Minitek system. J Clin Microbiol 24: 177, 1986. 13) Sako H, Tanaka M, Watanabe S, Oku K, Hishimoto T, Funabashi N. Application of ID test NF-18 to identification of the genus Corynebacterium. Media Circle 35: 191, 1990 (in Japanese). 14) Egawa T, Hara H, Kawase I, et al. Human pulmonary infection with Corynebacterium equi. Eur Respir J 3: 240, 1990. 15) Johnson WD, Cobbs CG, Arditi LI, Kaye D. Diphtheroid endo carditis after infection of a prosthetic heart valve. JAMA 203: 919, 1968. 16) Mizuno H, Wada I, Miyaji T. Acute suppurative otitis media with Corynebacterium pseudodiphtheriticum. Rinsho-to-Biseibutsu 15: 380, 1988 (in Japanese). 17) Scoy REV, Cohen SN, Geraci JE, Washington JA. Coryneform bacterial endocarditis. Mayo Clin Proc 52: 216, 1977. 18) Nishijima S, McGinley KJ, Leyden JJ. Group JK (Corynebacte rium jeikeium sp. nov.) isolated from Japanese skin flora. Jpn J Dermatol 99: 1121, 1989 (in Japanese).
Internal
Medicine
Vol. 31, No. 7 (July
1992)
