REVIEWS OF INFECTIOUS DISEASES • VOL. 12, NUMBER 3 • MAY-JUNE 1990
© 1990 by The University of Chicago. All rights reserved. 0162-0886/90/1203-0005$02.00
Peritonitis Due to Kluyvera ascorbata: Case Report and Review Ram Yogev and Steven Kozlowski
From the Department of Pediatrics, Northwestern University Medical School; the Division of Infectious Disease, Children's Memorial Hospital; and the Department oj Pediatrics, University oj Illinois Medical Center, Chicago, Illinois
Kluyvera, a new genus in the family Enterobacteriaceae, was formerly known as enteric group 8 and as API group 1. Although Kluyvera species have been isolated from various clinical specimens such as sputum, urine, stool, and blood, the clinical significance of these isolates has not been established. Recently, we treated a child who developed peritonitis due to Kluyvera ascorbata. The repeated isolation of the organism in pure culture from the peritoneal fluid and its isolation from postmortem subdiaphragmatic microabscesses suggest that Kluyvera can be clinically significant. Review of the literature clearly indicates that Kluyvera strains are infrequent but potentially dangerous pathogens in humans. Further experience is needed to determine the therapeutic efficacy of the various antibiotics to which these bacteria are sensitive in vitro.
Kluyvera was proposed in 1982 as a new genus in the family Enterobacteriaceae for a group of gram-
and creatinine, 1.3mg/dL. Chest radiograph showed cardiomegaly (cardiothoracic ratio, 0.75) and a diffuse alveolar infiltrate. Electrocardiogram showed atrial fibrillation. The patient was transferred to the intensive care unit, where the low serum sodium level did not respond to treatment with desoxycorticosterone acetate. On the fourth hospital day, she suddenly developed peripheral edema and became asystolic. She was successfully resuscitated and was then transferred to Children's Memorial Hospital. Upon her arrival, physical examination revealed a pale, afebrile, intubated girl with respirations of 40/min, a regular pulse of 120/min, and a blood pressure of 90/50 mm Hg. Both lung bases had decreased aeration and rales. Cardiac examination was unremarkable except for weak peripheral pulses. The abdomen was distended with shifting dullness and mild hepatomegaly. Neurologic examination showed decreased strength in both lower extremities, pes varus, and diffuse hyporeflexia. The patient was treated with hyperalimentation, severalcardiac medications, and multivitamins. Laboratory studies, including heavy metal screen, antinuclear antibody assay, plasma lipid profile, serum carnitine assay, lumbar puncture, and virus assays, were negative. Immunoglobulin levels were in the low-normal to normal range, with IgG at 680 mg/dL, IgA at 110mg/ dL, and IgM at 154 mg/dL. An electromyogram suggested peripheral neuropathy. An electrocardiogram showed atrial fibrillation, and an echocardiogram showed a very dilated heart with poor contrac-
negative bacilli formerly known as enteric group 8 (also known as API group 1) [1]. The majority of the isolates of this genus from patients have been from sputum, urine, and stool, with Kluyvera ascorbata the most common species. Many of the case reports describing patients with cultures positive for Kluyvera lack clinical and laboratory data to associate the bacterium with definite pathogenicity. We report on a child who developed peritonitis and urinary tract infection due to K. ascorbata, and we review the literature concerning the pathogenicity of Kluyvera species in humans. Case Report A 13-year-old girl who had previously appeared healthy was admitted to a local hospital for evaluation of 2 weeks of nausea and vomiting following 1 year of weight loss. On admission her weight was 28.5 kg (50th percentile for a 9-year-old). Except for revealing a very thin girl with an irregular pulse, the physical examination was negative. Laboratory data included the following: sodium, 123 meq/L; potassium, 6.2 meq/L; blood urea nitrogen, 59 mg/dL; Received for publication 28 January 1987and in revised form 16 August 1989. Please address requests for reprints to Dr. Ram Yogev, Division of Infectious Disease, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, Illinois 60614.
399
Yogev and Kozlowski
400
tility and a moderate pericardial effusion. The patient had multiple episodes of tachycardia (300/ min), which were thought to represent atrial flutter without atrioventricular node block. During two of these episodes, she became unresponsive without a measurable blood pressure. Multiple antiarrhythmic medications, pressors, intubation with ventilatory assistance, and a permanent pacemaker were required during her hospitalization. Twelvedays after transfer (hospital day 16), K. ascorbata was first recovered from a culture of an endotracheal tube aspirate; this finding was not associated with respiratory decompensation or chest radiographic changes. Three weeks later the patient developed prerenal azotemia secondary to congestive heart -failure, and peritoneal dialysis was instituted. Three days later the peritoneal fluid became cloudy, with 1,250 white blood cells/rum" (98070 neutrophils). Gram stain showed gram-negative bacilli, and K. ascorbata was isolated from the culture. (The isolate's identification was kindly confirmed by Dr. J. Farmer, Enteric Bacteriology Section, Centers for Disease Control, Atlanta.) The MICs (ug/ml.) of various antibiotics were as follows: gentamicin, 0.5; tobramycin, 1; amikacin, 2; trimethoprim-sulfamethoxazole, ~0.5/9.5; ampicillin, >64; cephalothin, 8; penicillin, >128; moxalactam, 1.25; and chloramphenicol, 2.0. Gentamicin (10 ug/ml.) was added to the dialysate, but the infection did not clear. Therefore, intravenous gentamicin was added to the regimen at a dosage that resulted in a peak blood level of 4 ug/rnl., Although the patient became afebrile, peritoneal fluid cultures remained positive for K. ascorbata. In addition, 1 week after the start of gentamicin therapy, two urine cultures yielded positive results, with >105 cfu of K. ascorbata/mL and the same antibiogram as had been seen with the earlier isolates. Although the gentamicin level in urine was found to be 78 ug/ml., urine cultures remained positive. An in vitro synergy study by the tube dilution method showed an additive effect between moxalactam and gentamicin for K. ascorbata. Therefore, moxalactam was added to the regimen. Two days later, however, the peritoneal fluid appeared stool-tinged, irreversible ventricular fibrillation developed, and the patient died. At autopsy, examination of the abdomen revealed a perforated ileum that was partially walled off by omentum. In addition, multiple small subdiaphragmatic abscesses were found. Cultures of the peritoneal fluid and several subdiaphragmatic abscesses
grew K. ascorbata and group D nonenterococcal Streptococcus. Lung histology showed extensive acute and organizing aspiration pneumonia. Lung tissue culture revealed a pure growth of K. ascorbata. Blood cultures were negative. Microscopic examination of the CNS showed degeneration of the posterior columns and the spinocerebellar tracts of the spinal cord. The cerebellar cortex also showed cell loss compatible with Friedreich's ataxia. Discussion In 1956 Asai and co-workers identified a group of polarly flagellated gram-negative bacilli that produced large amounts of a-ketoglutaric acid during glucose fermentation [2]. Because of their ability to ferment sugars, these organisms could not be placed in the genus Pseudomonas, and their polar flagella precluded assignment to the genus Escherichia. Asai and associates named these bacteria Kluyvera because of their similarity to an organism predicted in 1936 by Kluyver and van Niel [3], who postulated a group of polarly flagellated organisms in the genus Pseudomonas with a mixed-acid type of fermentation resembling that of Escherichia. In 1962 Asai et al. proposed that the new genus Kluyvera be transferred to the genus Escherichia because it had peritrichous rather than polar flagella [4]. Thus the genus Kluyvera was abolished and did not appear on the "Approved Lists of Bacterial Names" published in 1976 [5]. More recently, Farmer and co-workers [1], using DNA-DNA hybridization and biochemical tests, found that the K luyvera isolates were identical to isolates of what had been termed enteric group 8 (API group 1). Therefore, they proposed a new genus, Kluyvera, in the family Enterobacteriaceae. Strains of this genus are gram-negative rods, motile with peritrichous flagella, catalase-positive, and oxidasenegative. They grow on MacConkey agar and ferment D-glucose with the production of acid and gas. They are usually indole-positive, methyl red-positive, Voges Proskauer-negative, citrate-positive, H 2S (triple sugar iron)-negative, urea-negative, phenylalanine deaminase-negative, lysine decarboxylase-positive, arginine dihydrolase-negative, and ornithine decarboxylase-positive. They ferment many of the sugars and polyhydroxyl alcohols used in identification, and they are susceptible to many antibiotics [1]. The genus Kluyvera has two species: K. ascor-
Kluyvera in Human Injection
bata and K. cryocrescens. A third group, which is distinct by DNA hybridization, has been named Kluyvera species 3. The first two Kluyvera species are very close biochemically but can be differentiated by their ability to utilize ascorbate and to ferment D-glucose at 5°C and by differences in the zones of inhibition around disks of carbenicillin (100 ug per disk) and cephalothin (30 ug per disk). In addition, the strains can be differentiated by their response to irgasan [6]: K. ascorbata shows no zone of inhibition, while K. cryocrescens produces zones of ~15 mm around a disk containing 5 ug of irgasan. Most isolated strains of Kluyvera belong to K. ascorbata, and most K. ascorbata isolates have been derived from human clinical specimens, such as sputum, urine, and stool, and appear not to be of clinical significance. In vitro antimicrobial susceptibility studies of K. ascorbata strains suggest that they are almost alwayssensitiveto aminoglycosides, chloramphenicol, and tetracycline [1, 4]. The clinical significance of Kluyvera in most circumstances is unclear, although one isolate of K. ascorbata reported by Farmer et al. was cultured from a lung at autopsy [7]. Schwach [8] reported three isolates of enteric group 8 (K. ascorbata [1]) from the upper respiratory tract. Because the isolates were obtained in mixed culture with Klebsiella pneumoniae and were not isolated on repeated attempts, they were not considered pathogens. Braunstein et al. [9] reported two isolates of what was termed a Citrobacter-Enterobacter intermediate, later reclassified as K. ascorbata [1]. One isolate was from sputum of a 6-year-oldchild with pulmonary tuberculosis. Review of this patient's records suggests that the sputum isolate was a contaminant. The other isolate, from gallbladder drainage of a 63-year-old woman with acute pancreatitis, was considered a pathogen. The isolation of pure K. cryocrescens from the gallbladder of another 76year-old woman with acute cholecystitis [10] suggests that strains of Kluyvera can be pathogens in humans. Five of the 144 Kluyvera strains reported by Farmer [7] were isolated from blood (three strains of K. ascorbata, one of K. cryocrescens, and one of Kluyvera species 3). No clinical data were provided to allow assessment of these isolates. In addition, K. cryocrescens was isolated from a blood sample drawn from an infant with Broviac catheter-related infection [11], and Kluyvera species were grown from blood and suprapubic urine aspirate of another infant with sepsis and urinary tract infection [12]. These seven blood isolates further suggest that
401
Kluyvera can cause human infections. The potential ability of Kluyvera to cause diarrhea was reported by Fainstein et al. [13], who isolated Kluyvera species from the stools of 11 patients with and without diarrhea. Most of these patients were elderly, neutropenic, and febrile. A soft-tissue infection caused by Kluyvera species in a previously healthy host [14] is another indication of the organism's pathogenicity. The patient described herein appears to represent the first well-documented case of definite infection with K. .ascorbata. The repeated isolations of this microbe in pure culture from the peritoneal fluidtogether with peritoneal fluid pleocytosis with predominance of neutrophils and the postmortem demonstration of both subdiaphragmatic microabscesses and lung cultures also yielding K. ascorbata - indicate that this organism was definitely a pathogen in our patient. Although serum immunoglobulin levelswere within the normal range, the possibility that this girl contracted her infection because of an immunocompromised status cannot be ruled out. In vitro data documented that the K. ascorbata isolate from our patient was sensitive to gentamicin, but this antibiotic - in appropriate doses - did not eradicate the organism from either the peritoneal dialysate or the urine. This failure may have been attributable to the presence of foreign bodies or may have indicated that with Kluyvera (as with Salmonel/a) a discordance exists between the in vitro sensitivity to aminoglycosides and the in vivo efficacy of these antibiotics. Additional clinical experience will be necessary in order to formulate therapeutic recommendations. It is clear that Kluyvera strains are infrequent but potentially dangerous pathogens. Further experience will be needed to determine their potential pathogenicity in the normal as well as the immunocompromised host and to assess the therapeutic efficacy of antibiotics that show in vitro activity. References
1. Farmer 11 III, Fanning GR, Huntley-Carter GP, Holmes B, Hickman FW, Richard C, Brenner OJ. K/uyvera, a new (redefined) genus in the family Enterobacteriaceae: identification of K/uyvera ascorbata sp. nov. and K/uyvera cryocrescens sp. nov. in clinical specimens. J Clin Microbiol 1982;12:919-33 2. Asai T, Okumura S, Tsunoda T. On a new genus, Kluyvera. Proceedings of the Japanese Academy 1956;32:488-93 3. Kluyver AJ, van Niel CB. Prospects for a natural system of classification of bacteria. Zentralbl Bakteriol [orig] 1936; 94:369-403
402
4. Asai T, Iizuka H, Komagata K. The flagellation of genus Kluyvera. Journal of General and Applied Microbiology (Japan) 1962;8:187-91 5. Steigerwalt AG, Fanning GR, Fife-Asbury MA, Brenner DJ. DNA relatedness among species of Enterobacterand Serratia. Can J Microbiol 1976;22:121-37 6. Altweoo M, Zollenger-Iten J, Graevenita A. Differentiation of Kluyvera cryocrescens from Kluyvera ascorbata by irgasan susceptibility testing. Annales de l'Institut Pas 1986;137:159-68 7. Farmer JJ III, Davis BR, Hickman-Brenner FW, McWhorter A, Huntley-Carter GP, Asbury MA, Riddle C, WathenGrady HG, Fanning GR, Elias C, Steigerwalt AG, O'Hara CM, Morris GK, Smith PB, Brenner OJ. Biochemical identification of new species and biogroups of Enterobacteriaceae isolated from clinical specimens. J Clin Microbiol 1985;21:46-76 8. Schwach T. Case report [letter no. 16]. Clinical Microbiology 1979;1:4-5
Yogev and Kozlowski
9. Braunstein H, Tomasulo M, Scott S, Chadwick MP. A biotype of Enterobacteriaceae intermediate between Citrobacter and Enterobacter. Am J Clin Pat hoi 1980;73:114-6 10. Thaller R, Berlutti F, Thaller Me. A Kluyvera cryocrescens strain from a gall-bladder infection. Eur J Epidemiol1988; 1:124-6 II. Wong VK. Broviac catheter infection with Kluyvera cryocrescens: a case report. J Clin Microbiol 1987;25:1115-6 12. Tristram DA, Forbes BA. Kluyvera: a case report of urinary tract infection and sepsis. Pediatr Infect Dis 1988;7:297-8 13. Fainstein V, Hopfer RL, Mills K, Bodey GP. Colonization by or diarrhea due to Kluyvera species. J Infect Dis 1982; 145:127 14. Luttrell RE, Rannick GA, Soto-Hernandez JL, VergheseA. Kluyvera species soft tissue infection: case report and review. J Clin Microbiol 1988;26:2650-1
© 1990 by The University of Chicago. All rights reserved. 0162-0886/90/1203-0005$02.00
Peritonitis Due to Kluyvera ascorbata: Case Report and Review Ram Yogev and Steven Kozlowski
From the Department of Pediatrics, Northwestern University Medical School; the Division of Infectious Disease, Children's Memorial Hospital; and the Department oj Pediatrics, University oj Illinois Medical Center, Chicago, Illinois
Kluyvera, a new genus in the family Enterobacteriaceae, was formerly known as enteric group 8 and as API group 1. Although Kluyvera species have been isolated from various clinical specimens such as sputum, urine, stool, and blood, the clinical significance of these isolates has not been established. Recently, we treated a child who developed peritonitis due to Kluyvera ascorbata. The repeated isolation of the organism in pure culture from the peritoneal fluid and its isolation from postmortem subdiaphragmatic microabscesses suggest that Kluyvera can be clinically significant. Review of the literature clearly indicates that Kluyvera strains are infrequent but potentially dangerous pathogens in humans. Further experience is needed to determine the therapeutic efficacy of the various antibiotics to which these bacteria are sensitive in vitro.
Kluyvera was proposed in 1982 as a new genus in the family Enterobacteriaceae for a group of gram-
and creatinine, 1.3mg/dL. Chest radiograph showed cardiomegaly (cardiothoracic ratio, 0.75) and a diffuse alveolar infiltrate. Electrocardiogram showed atrial fibrillation. The patient was transferred to the intensive care unit, where the low serum sodium level did not respond to treatment with desoxycorticosterone acetate. On the fourth hospital day, she suddenly developed peripheral edema and became asystolic. She was successfully resuscitated and was then transferred to Children's Memorial Hospital. Upon her arrival, physical examination revealed a pale, afebrile, intubated girl with respirations of 40/min, a regular pulse of 120/min, and a blood pressure of 90/50 mm Hg. Both lung bases had decreased aeration and rales. Cardiac examination was unremarkable except for weak peripheral pulses. The abdomen was distended with shifting dullness and mild hepatomegaly. Neurologic examination showed decreased strength in both lower extremities, pes varus, and diffuse hyporeflexia. The patient was treated with hyperalimentation, severalcardiac medications, and multivitamins. Laboratory studies, including heavy metal screen, antinuclear antibody assay, plasma lipid profile, serum carnitine assay, lumbar puncture, and virus assays, were negative. Immunoglobulin levels were in the low-normal to normal range, with IgG at 680 mg/dL, IgA at 110mg/ dL, and IgM at 154 mg/dL. An electromyogram suggested peripheral neuropathy. An electrocardiogram showed atrial fibrillation, and an echocardiogram showed a very dilated heart with poor contrac-
negative bacilli formerly known as enteric group 8 (also known as API group 1) [1]. The majority of the isolates of this genus from patients have been from sputum, urine, and stool, with Kluyvera ascorbata the most common species. Many of the case reports describing patients with cultures positive for Kluyvera lack clinical and laboratory data to associate the bacterium with definite pathogenicity. We report on a child who developed peritonitis and urinary tract infection due to K. ascorbata, and we review the literature concerning the pathogenicity of Kluyvera species in humans. Case Report A 13-year-old girl who had previously appeared healthy was admitted to a local hospital for evaluation of 2 weeks of nausea and vomiting following 1 year of weight loss. On admission her weight was 28.5 kg (50th percentile for a 9-year-old). Except for revealing a very thin girl with an irregular pulse, the physical examination was negative. Laboratory data included the following: sodium, 123 meq/L; potassium, 6.2 meq/L; blood urea nitrogen, 59 mg/dL; Received for publication 28 January 1987and in revised form 16 August 1989. Please address requests for reprints to Dr. Ram Yogev, Division of Infectious Disease, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, Illinois 60614.
399
Yogev and Kozlowski
400
tility and a moderate pericardial effusion. The patient had multiple episodes of tachycardia (300/ min), which were thought to represent atrial flutter without atrioventricular node block. During two of these episodes, she became unresponsive without a measurable blood pressure. Multiple antiarrhythmic medications, pressors, intubation with ventilatory assistance, and a permanent pacemaker were required during her hospitalization. Twelvedays after transfer (hospital day 16), K. ascorbata was first recovered from a culture of an endotracheal tube aspirate; this finding was not associated with respiratory decompensation or chest radiographic changes. Three weeks later the patient developed prerenal azotemia secondary to congestive heart -failure, and peritoneal dialysis was instituted. Three days later the peritoneal fluid became cloudy, with 1,250 white blood cells/rum" (98070 neutrophils). Gram stain showed gram-negative bacilli, and K. ascorbata was isolated from the culture. (The isolate's identification was kindly confirmed by Dr. J. Farmer, Enteric Bacteriology Section, Centers for Disease Control, Atlanta.) The MICs (ug/ml.) of various antibiotics were as follows: gentamicin, 0.5; tobramycin, 1; amikacin, 2; trimethoprim-sulfamethoxazole, ~0.5/9.5; ampicillin, >64; cephalothin, 8; penicillin, >128; moxalactam, 1.25; and chloramphenicol, 2.0. Gentamicin (10 ug/ml.) was added to the dialysate, but the infection did not clear. Therefore, intravenous gentamicin was added to the regimen at a dosage that resulted in a peak blood level of 4 ug/rnl., Although the patient became afebrile, peritoneal fluid cultures remained positive for K. ascorbata. In addition, 1 week after the start of gentamicin therapy, two urine cultures yielded positive results, with >105 cfu of K. ascorbata/mL and the same antibiogram as had been seen with the earlier isolates. Although the gentamicin level in urine was found to be 78 ug/ml., urine cultures remained positive. An in vitro synergy study by the tube dilution method showed an additive effect between moxalactam and gentamicin for K. ascorbata. Therefore, moxalactam was added to the regimen. Two days later, however, the peritoneal fluid appeared stool-tinged, irreversible ventricular fibrillation developed, and the patient died. At autopsy, examination of the abdomen revealed a perforated ileum that was partially walled off by omentum. In addition, multiple small subdiaphragmatic abscesses were found. Cultures of the peritoneal fluid and several subdiaphragmatic abscesses
grew K. ascorbata and group D nonenterococcal Streptococcus. Lung histology showed extensive acute and organizing aspiration pneumonia. Lung tissue culture revealed a pure growth of K. ascorbata. Blood cultures were negative. Microscopic examination of the CNS showed degeneration of the posterior columns and the spinocerebellar tracts of the spinal cord. The cerebellar cortex also showed cell loss compatible with Friedreich's ataxia. Discussion In 1956 Asai and co-workers identified a group of polarly flagellated gram-negative bacilli that produced large amounts of a-ketoglutaric acid during glucose fermentation [2]. Because of their ability to ferment sugars, these organisms could not be placed in the genus Pseudomonas, and their polar flagella precluded assignment to the genus Escherichia. Asai and associates named these bacteria Kluyvera because of their similarity to an organism predicted in 1936 by Kluyver and van Niel [3], who postulated a group of polarly flagellated organisms in the genus Pseudomonas with a mixed-acid type of fermentation resembling that of Escherichia. In 1962 Asai et al. proposed that the new genus Kluyvera be transferred to the genus Escherichia because it had peritrichous rather than polar flagella [4]. Thus the genus Kluyvera was abolished and did not appear on the "Approved Lists of Bacterial Names" published in 1976 [5]. More recently, Farmer and co-workers [1], using DNA-DNA hybridization and biochemical tests, found that the K luyvera isolates were identical to isolates of what had been termed enteric group 8 (API group 1). Therefore, they proposed a new genus, Kluyvera, in the family Enterobacteriaceae. Strains of this genus are gram-negative rods, motile with peritrichous flagella, catalase-positive, and oxidasenegative. They grow on MacConkey agar and ferment D-glucose with the production of acid and gas. They are usually indole-positive, methyl red-positive, Voges Proskauer-negative, citrate-positive, H 2S (triple sugar iron)-negative, urea-negative, phenylalanine deaminase-negative, lysine decarboxylase-positive, arginine dihydrolase-negative, and ornithine decarboxylase-positive. They ferment many of the sugars and polyhydroxyl alcohols used in identification, and they are susceptible to many antibiotics [1]. The genus Kluyvera has two species: K. ascor-
Kluyvera in Human Injection
bata and K. cryocrescens. A third group, which is distinct by DNA hybridization, has been named Kluyvera species 3. The first two Kluyvera species are very close biochemically but can be differentiated by their ability to utilize ascorbate and to ferment D-glucose at 5°C and by differences in the zones of inhibition around disks of carbenicillin (100 ug per disk) and cephalothin (30 ug per disk). In addition, the strains can be differentiated by their response to irgasan [6]: K. ascorbata shows no zone of inhibition, while K. cryocrescens produces zones of ~15 mm around a disk containing 5 ug of irgasan. Most isolated strains of Kluyvera belong to K. ascorbata, and most K. ascorbata isolates have been derived from human clinical specimens, such as sputum, urine, and stool, and appear not to be of clinical significance. In vitro antimicrobial susceptibility studies of K. ascorbata strains suggest that they are almost alwayssensitiveto aminoglycosides, chloramphenicol, and tetracycline [1, 4]. The clinical significance of Kluyvera in most circumstances is unclear, although one isolate of K. ascorbata reported by Farmer et al. was cultured from a lung at autopsy [7]. Schwach [8] reported three isolates of enteric group 8 (K. ascorbata [1]) from the upper respiratory tract. Because the isolates were obtained in mixed culture with Klebsiella pneumoniae and were not isolated on repeated attempts, they were not considered pathogens. Braunstein et al. [9] reported two isolates of what was termed a Citrobacter-Enterobacter intermediate, later reclassified as K. ascorbata [1]. One isolate was from sputum of a 6-year-oldchild with pulmonary tuberculosis. Review of this patient's records suggests that the sputum isolate was a contaminant. The other isolate, from gallbladder drainage of a 63-year-old woman with acute pancreatitis, was considered a pathogen. The isolation of pure K. cryocrescens from the gallbladder of another 76year-old woman with acute cholecystitis [10] suggests that strains of Kluyvera can be pathogens in humans. Five of the 144 Kluyvera strains reported by Farmer [7] were isolated from blood (three strains of K. ascorbata, one of K. cryocrescens, and one of Kluyvera species 3). No clinical data were provided to allow assessment of these isolates. In addition, K. cryocrescens was isolated from a blood sample drawn from an infant with Broviac catheter-related infection [11], and Kluyvera species were grown from blood and suprapubic urine aspirate of another infant with sepsis and urinary tract infection [12]. These seven blood isolates further suggest that
401
Kluyvera can cause human infections. The potential ability of Kluyvera to cause diarrhea was reported by Fainstein et al. [13], who isolated Kluyvera species from the stools of 11 patients with and without diarrhea. Most of these patients were elderly, neutropenic, and febrile. A soft-tissue infection caused by Kluyvera species in a previously healthy host [14] is another indication of the organism's pathogenicity. The patient described herein appears to represent the first well-documented case of definite infection with K. .ascorbata. The repeated isolations of this microbe in pure culture from the peritoneal fluidtogether with peritoneal fluid pleocytosis with predominance of neutrophils and the postmortem demonstration of both subdiaphragmatic microabscesses and lung cultures also yielding K. ascorbata - indicate that this organism was definitely a pathogen in our patient. Although serum immunoglobulin levelswere within the normal range, the possibility that this girl contracted her infection because of an immunocompromised status cannot be ruled out. In vitro data documented that the K. ascorbata isolate from our patient was sensitive to gentamicin, but this antibiotic - in appropriate doses - did not eradicate the organism from either the peritoneal dialysate or the urine. This failure may have been attributable to the presence of foreign bodies or may have indicated that with Kluyvera (as with Salmonel/a) a discordance exists between the in vitro sensitivity to aminoglycosides and the in vivo efficacy of these antibiotics. Additional clinical experience will be necessary in order to formulate therapeutic recommendations. It is clear that Kluyvera strains are infrequent but potentially dangerous pathogens. Further experience will be needed to determine their potential pathogenicity in the normal as well as the immunocompromised host and to assess the therapeutic efficacy of antibiotics that show in vitro activity. References
1. Farmer 11 III, Fanning GR, Huntley-Carter GP, Holmes B, Hickman FW, Richard C, Brenner OJ. K/uyvera, a new (redefined) genus in the family Enterobacteriaceae: identification of K/uyvera ascorbata sp. nov. and K/uyvera cryocrescens sp. nov. in clinical specimens. J Clin Microbiol 1982;12:919-33 2. Asai T, Okumura S, Tsunoda T. On a new genus, Kluyvera. Proceedings of the Japanese Academy 1956;32:488-93 3. Kluyver AJ, van Niel CB. Prospects for a natural system of classification of bacteria. Zentralbl Bakteriol [orig] 1936; 94:369-403
402
4. Asai T, Iizuka H, Komagata K. The flagellation of genus Kluyvera. Journal of General and Applied Microbiology (Japan) 1962;8:187-91 5. Steigerwalt AG, Fanning GR, Fife-Asbury MA, Brenner DJ. DNA relatedness among species of Enterobacterand Serratia. Can J Microbiol 1976;22:121-37 6. Altweoo M, Zollenger-Iten J, Graevenita A. Differentiation of Kluyvera cryocrescens from Kluyvera ascorbata by irgasan susceptibility testing. Annales de l'Institut Pas 1986;137:159-68 7. Farmer JJ III, Davis BR, Hickman-Brenner FW, McWhorter A, Huntley-Carter GP, Asbury MA, Riddle C, WathenGrady HG, Fanning GR, Elias C, Steigerwalt AG, O'Hara CM, Morris GK, Smith PB, Brenner OJ. Biochemical identification of new species and biogroups of Enterobacteriaceae isolated from clinical specimens. J Clin Microbiol 1985;21:46-76 8. Schwach T. Case report [letter no. 16]. Clinical Microbiology 1979;1:4-5
Yogev and Kozlowski
9. Braunstein H, Tomasulo M, Scott S, Chadwick MP. A biotype of Enterobacteriaceae intermediate between Citrobacter and Enterobacter. Am J Clin Pat hoi 1980;73:114-6 10. Thaller R, Berlutti F, Thaller Me. A Kluyvera cryocrescens strain from a gall-bladder infection. Eur J Epidemiol1988; 1:124-6 II. Wong VK. Broviac catheter infection with Kluyvera cryocrescens: a case report. J Clin Microbiol 1987;25:1115-6 12. Tristram DA, Forbes BA. Kluyvera: a case report of urinary tract infection and sepsis. Pediatr Infect Dis 1988;7:297-8 13. Fainstein V, Hopfer RL, Mills K, Bodey GP. Colonization by or diarrhea due to Kluyvera species. J Infect Dis 1982; 145:127 14. Luttrell RE, Rannick GA, Soto-Hernandez JL, VergheseA. Kluyvera species soft tissue infection: case report and review. J Clin Microbiol 1988;26:2650-1
