Central venous catheter infection in a child: case report and review of Kluyvera infection in children. (Case Report).

Abstract

Kluyvera is an opportunistic pathogen that can occur in immunosuppressed as well as immunocompetent hosts. We report a case of Kluyvera species infection involving a central venous catheter, and we review the literature on Kluyvera infections in children. Our case demonstrates that removal of the central venous catheter was necessary to eradicate the infection and hasten the resolution of refractory neutropenia. The spectrum of disease due to Kluyvera infection in children includes central venous catheter infection and/or sepsis, urinary tract infection, enteritis, and, in one instance, fatal peritonitis. It is clear on the basis of our case report that uncommon, opportunistic organisms such as Kluyvera can be significant pathogens.

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Kluyvera, a genus in the family Enterobacteriaceae, is a Gram-negative bacillus previously described as an opportunistic pathogen. Kluyvera has been isolated from a variety of human specimens (most commonly sputum, where it is unlikely to be clinically significant). Kluyvera has been found in food, water, soil, sewage, and hospital environments. After Farmer et al's (1) redefinition of the Kluyvera genus in 1981, reports of its isolation in other clinical specimens began to appear. In 1998, West et a1 (2) reviewed 18 cases of Kluyvera infection in humans (primarily in adults). We report a case of this disease in a child and review the literature regarding Kluyvera infection exclusively in children. Our case demonstrates that opportunistic organisms such as Kluyvera species can infect a central venous catheter in an immunosuppressed patient and cause significant illness.

Discussion

In 1981, Farmer et al (1) proposed a new genus for the group of organisms that formerly had been termed enteric Group 8. These organisms were compared with strains of Kluyvera, a group of organisms that had been discovered in Japan and placed in the genus Escherichia. After extensive studies of the organisms, it was found that the isolates did not fit any of the existing species in the family Enterobacteriaceae. Therefore, Farmer et al (1) proposed Kluyvera as a new genus and, on the basis of DNA hybridization, further speciated it into three groups: Kluyvera ascorbate, Kluyvera cryo-crescens, and Kluyvera species Group 3. Kluyvera organisms are Gram-negative, motile bacilli with peritrichous flagella that have a biochemica[ profile similar to that of other Enterobacteriaceae. They are oxidase-negative and catalase-positive, and they ferment glucose. (3) The most common isolates in humans have been found in sputum, although urine, stool, throat swabs, and blood have grown Kluyvera species. (4)

In our review of seven pediatric cases, (4-9) we noted that four isolates were from blood (including our case), four were from urine, and one each were from peritoneal fluid, endo-tracheal aspirate, autopsy lung tissue, and stool (Table 2). No isolates from the central nervous system have been reported in children or adults. (2) The ages of the patients ranged from 3 weeks to 17 years. Two had no underlying disease, one had a malignancy, and the remainder of the patients had a variety of other nonimmunosuppressive conditions (Table 2). The clinical presentations included diarrhea, sepsis, urinary tract infections, and peritonitis. Two of the seven patients died. One death was attributed to infection with Kluyvera species, as evidenced by the isolation of Kluyvera organisms from multiple organ sites at autopsy. (5) The other patient died as a result of cardiopulmonary arrest unrelated to the Kluyvera species infection. (6) It is apparent that Kluyvera causes infection in both immunocompromised and immunocompet ent hosts.

In the cases in which antibiotic sensitivities were reported, the Kluyvera species was found to be resistant to ampicillin; (2,4,5,7,8) by contrast, it was very sensitive to the aminoglycosides. The latter antibiotics should be considered the treatment of choice, pending the report of antibiotic sensitivities. In our case, the Kluyvera species was also sensitive to cephalosporins, quinolones, and trimethoprim/sulfamethoxazole.

A question might arise about the mechanism of the catheter infection in our case. Kluyvera is found in sewage, soil, food, and feces. Our patient with neutropenia had mild abdominal pain without any other clinical evidence of colitis (eg, diarrhea, bloody stool). The mild abdominal pain resolved within 24 hours. Kluyvera and B. cereus can be found in the gastrointestinal tract. Because of the mild nature of the abdominal symptoms and their quick resolution, however, we do not think that this was the source of the CVC infection. Furthermore, we did not consider the B. cereus as a cause of the catheter infection. The B. cereus cleared rapidly with the blood cultures negative for the organism after less than 24 hours of treatment with antibiotics to which it was not susceptible. Our laboratory did not speciate the Gram-negative bacilli from the stool culture; thus, it is unknown if the gastrointestinal tract was colonized with Kluyvera organisms. We do not think that the gastrointestinal tract was the source of the Kluyvera species infection. We propose that the patient's port site, which was found to be erythematous at the time of admission, could have been contaminated from the environment.

There has been only one other report of a child with a central-line infection due to Kluyvera species. In 1987, Wong (6) described a 17-month-old child with congenital heart disease who developed a Kluyvera species infection in a Broviac catheter. The patient received 10 days of treatment with ampicillin and gentamicin through the Broviac catheter. Two days after treatment, the catheter was removed, and a culture of the tip was sterile. This case suggests that CVC infection by Kluyvera species may be managed successfully with antibiotics administered through the infected catheter. In our case, however, we noted that after apparent clearing of the CVC infection (blood cultures were negative for the Kluyvera organism while antibiotics were infused through the CVC), the patient relapsed while undergoing appropriate therapy. The relapse was temporally associated with the change in administration of antibiotics from the CVC to a peripheral vein, which was necessitated by the reappearance of inflammation at the CVC site. It seems that antibiotic therapy had only suppressed the growth of the organism, thus making it difficult to isolate the organism from the blood cultures obtained through the catheter. In retrospect, the reappearance of erythema at the CVC site on hospital Day 12 suggests that perhaps the catheter infection had persisted and that systemic therapy had not been effective. It is again noted that the CVC in this patient was not tunneled. After discontinuing the administration of antibiotics through the catheter, the infection became apparent within 24 hours, manifested as fever and a blood culture from the catheter positive for Kluyvera species. After removal of the CVC, the patient defervesced and the neutropenia improved.

One recent innovation in the treatment of catheter-related infection is antibiotic lock therapy. (10) Antibiotic lock therapy involves installing in the catheter lumen a high concentration of an antibiotic to which the causative microbe is susceptible. The antibiotics are installed, or "locked," into the catheter lumen during periods when the catheter is not used. Little information is available on the effectiveness of antibiotic lock therapy in the setting of nonbacteremic, nontunneled catheter infection. (10,11) Further studies are needed to determine whether antibiotic lock therapy can be used for catheter salvage.

Conclusions

Kluyvera is an uncommon, opportunistic pathogen in immunosuppressed and immunocompetent hosts. The spectrum of diseases caused by Kluyvera in children includes CVC infection and/or sepsis, urinary tract infection, enteritis, and, in one instance, fatal peritonitis. Our case suggests that the catheter apparently was sterile only while antibiotics were being infused through it. We speculate that a persistently infected catheter could contribute to delayed resolution of neutropenia, despite a prolonged course of granulocyte colony-stimulating factor. Although clinical experience with CVC-associated Kluyvera species infection is limited, we think that reluctance to remove a CVC infected with this organism could potentially increase the patient's risk for refractory neutropenia. Our case shows that uncommon opportunistic organisms such as Kluyvera can be significant pathogens.

Table 1

Clinical course (a)

                                        Hospital day

                        1         2        3           4       5

Laboratory tests
 Max T ([degrees]F)   104.8     104.4    102.8     102.9     103.4
 WBC (X 10 (9)/L)       0.153     0.10     0.10      0.20      0.11
CVC                  BAC, KLU  BAC, KLU   KLU         --      KLU
Antibiotics
 Oxacillin              +         +        +
 Clindamycin                                           +       +
 Tobramycin             +         +        +           +       +
 Vancomycin

                                        Hospital day

                       6         7        8         9         10

Laboratory tests
 Max T ([degrees]F)  103.6     101.3     99.7      98.3      98.9
 WBC (X 10 (9)/L)      0.23      0.43     0.25      0.20      0.26
CVC                   --        --        --        --        --
Antibiotics
 Oxacillin
 Clindamycin           +
 Tobramycin            +         +        +         +         +
 Vancomycin            +         +        +         +         +

                                        Hospital day

                      11        12        13        14        15

Laboratory tests
 Max T ([degrees]F)  98.8      99.4      99.5      100.1     98.8
 WBC (X 10 (9)/L)     0.60      0.39      0.49       1.19     1.51
CVC                   --        --       KLU        --        --
Antibiotics
 Oxacillin
 Clindamycin
 Tobramycin           +         +         +          +        +
 Vancomycin           +         +         +          +        +

                      Hospital
                        day

                      16

Laboratory tests
 Max T ([degrees]F)  99.3
 WBC (X 10 (9)/L)     2.21
CVC                   --
Antibiotics
 Oxacillin
 Clindamycin
 Tobramycin           +
 Vancomycin           +

(a)WBC, white blood cell count; Max T, maximum, temperature; KLU,
Kluyvera species; BAC, Bacillus species; CVC, central venous catheter.

(b)Access changed to peripheral.

(c)CVC removed.

Table 2

Pediatric cases of infection with Kluyvera species (a)

                               Patient       Underlying
Case report (ref. no.)         age/sex         disease

Aevaliotis et al, 1985 (7)      3 wk/F  None
Wang, 1987 (6)                 17 mo/M  Congenital heart
                                         disease
Tristram and Forbes, 1988 (8)  11 mo/F  Vesicoureteral reflux

Dollberg et al, 1990 (4)        5 yr/F  None
Yogev and Kozlowski            13 yr/M  Friedrich's ataxia
  1990 (5)

Ortega Calvo et al, 1999 (9)   10 y/F   Proteinuria

Brooks and Feldman, 2003,      17 yr/F  Ewing's sarcoma
 present ease

                                  Clinical             Source of
Case report (ref. no.)            diagnosis            organism

Aevaliotis et al, 1985 (7)     Diarrhea         Stool
Wang, 1987 (6)                 CVC infection/   Blood
                                sepsis
Tristram and Forbes, 1988 (8)  Sepsis/UTI       Blood/urine

Dollberg et al, 1990 (4)       Pyelonephritis   Urine
Yogev and Kozlowski            Peritonitis/UTI  Respiratory secretions,
  1990 (5)                                       peritoneal fluid,
                                                 urine, lung tissue
Ortega Calvo et al, 1999 (9)   UTI              Urine

Brooks and Feldman, 2003,      CVC infection/   Blood
 present ease                   sepsis


Case report (ref. no.)          Treatment          Outcome

Aevaliotis et al, 1985 (7)     Symptomatic  Cured
Wang, 1987 (6)                 Ampicillin,  Died (cardiopulmonary
                                gentamicin   arrest)
Tristram and Forbes, 1988 (8)  Tobramycin,  Cured
                                cefoxitin
Dollberg et al, 1990 (4)       Cefazolin    Cured
Yogev and Kozlowski            Moxalactam,  Died (perforated
  1990 (5)                      gentamicin   ileum, peritonitis,
                                             pneumonia)
Ortega Calvo et al, 1999 (9)   Cefuroxime   Cured
                                axetil
Brooks and Feldman, 2003,      Tobramycin   Cured
 present ease

(a)UTI, uninary tract infection; CVC, central venous catheter.

Accepted January 21, 2002.

References

(1.) Farmer JJ III, Fanning GR, Huntley-Carter GP, Holmes B, Hickman FW, Richard C, et al. Kluyvera, a new (redefined) genus in the family Enterobacteriaceae: Identification of Kluyvera ascorbata sp. nov. and Kluyvera cryocrescens sp. nov. in clinical specimens. J Clin Microbiol 1981;13:919-933.

(2.) West BC, Vijayan H, Shekar R. Kluyvera cyocrescens finger infection: Case report and review of eighteen Kluyvera infections in human beings. Diagn Microbiol Infect Dis 1998;32:237-241.

(3.) Balows A, Hausler WJ Jr, Herrmann KL, Isenberg HD, Shadomy HJ (eds). Manual of Clinical Microbiology. Washington, DC, American Society for Microbiology, 1991, ed 5, pp 376-377.

(4.) Dollberg S, Gandacu A, Klar A. Acute pyelonephritis due to a Kluyvera species in a child. Eur J Clin Microbial Infect Dis 1990;9:281-283.

(5.) Yogev R, Kozlowski S. Peritonitis due to Kluyvera ascorbata: Case report and review. Rev Infect Dis 1990;12:399-402.

(6.) Wong VK. Broviac catheter infection with Kluyvera cryocrescens: A case report. J Clin Microbiol 1987;25:11l5-1116.

(7.) Aevaliotis A, Belle AM, Chanione JP, et al. Kluyvera ascorbata isolated from a baby with diarrhea. Clin Microbial Newsl 1985;7:51.

(8.) Tristram DA, Forbes BA. Kluyvera: A case report of urinary tract infection and sepsis. Pediatr Infect Dis J 1988;7:297-298.

(9.) Ortega Calvo M, Delgado Zamora R, Fernandez Arance P, Elgorriaga Guillen LJ, Del Valle Vazquez L, Gutierrez Caracuel J. Kluyvera cryocrescens: A positive urine culture in a young girl with persistent proteinuria [in Spanish]. Actas Urol Esp 1999;23:528-531.

(10.) Mermel LA, Farr BM, Sherertz RJ, Raad II, O'Grady N, Harris JS, et al. Guidelines for the management of intravascular catheter-related infections: Society for Healthcare Epidemiology of America. Clin Infect Dis 2001;32:1249-1272.

(11.) Johnson DC, Johnson FL, Goldman S. Preliminary results treating persistent central venous catheter infections with the antibiotic lock technique in pediatric patients. Pediatr Infect Dis J 1994;13:930-931.

RELATED ARTICLE: Key Points

* Kluyvera is an uncommon, opportunistic organism that can be a significant pathogen.

* Six previously reported pediatric cases of Kluyvera infection are reviewed here.

* The new case described here demonstrates that removal of the central venous catheter was necessary to eradicate the organism and improve the patient's neutropenia.

Case Report

A 17-year-old white girl with Ewing's sarcoma was admitted to the hospital with fever and neutropenia 4 days after undergoing chemotherapy with etoposide, mesna, and ifosfamide. On the previous day, the patient had been evaluated in the clinic for mild erythema of her peripheral access system port site (henceforth referred to as the central venous catheter [CVC]). The patient had a peripherally inserted, nontunneled CVC. At admission, the patient's temperature was 102[degrees]F, her pulse was 142 beats/mm, her respiratory rate was 24 breaths/mm, and her blood pressure was 110/68 mm Hg. Her physical examination was unremarkable, except for mild tenderness over the left lower abdominal quadrant and erythema over the CVC site, which were unchanged from the previous day. Hepatosplenomegaly, bruising, and petechiae were absent. The complete blood cell count revealed the following values: white blood cell count, 0.153 X [10.sup.9]/L, with an absolute neutrophil count (ANC) of 0; hemoglobin, 10.0 g/L; hematocrit, 28 %; and platelets, 10.6 X [10.sup.9]/L. The chest x-ray film was normal. Blood cultures were obtained from the patient's CVC and from a peripheral vein. The samples were inoculated into aerobic and anaerobic blood culture collection bottles. A skin culture was obtained from an erythematous area at the CVC site. Organisms were identified with the use of routine laboratory methods.

The initial treatment consisted of tobramycin and oxacillin. All antibiotics were infused through the CVC on an interval basis. Supportive therapy included transfusions of red blood cells and platelets as well as daily treatment with granulocyte colony-stimulating factor, without apparent response in her blood cell count. Gram-positive and Gram-negative bacilli were isolated from the initial CVC blood culture. The peripheral blood culture and the culture from the CVC site were negative for microorganisms. The patient's CVC was infusing well. The patient's erythema resolved within 24 hours of admission. Despite treatment with antibiotics, however, the patient remained febrile.

The Gram-positive bacillus was identified as a Bacillus cereus (B. cereus). Antibiotic treatment was changed from oxacillin to clindamycin on hospital Day 3. On the sixth hospital day, the Gram-negative bacillus was identified as Kluyvera species susceptible to tobramycin and resistant to ampicillin. At this time, the infectious disease service was consulted; the recommendation was that dindamycin therapy be discontinued and vancomycin treatment, to which the B. cereus was susceptible, be initiated. The role of B. cereus is unclear, because it cleared rapidly with blood cultures negative for B. cereus after less than 24 hours of treatment with antibiotics to which the organism was not susceptible. The patient was considered to have a CVC infection. The physicians elected to treat the infection without removing the CVC by using periodic systemic infusions of tobramycin and vancomycin through the CVC.

The blood culture from the CVC remained positive for Kluyvera species until the sixth hospital day, at which time the only additional peripheral blood culture was drawn, and it was again negative for this organism. The patient remained febrile for another 2 days, however (Table 1). There was no clinical evidence of other foci of infection. Thereafter, the patient was afebrile, clinically stable, and the blood cultures from the CVC were negative for Kluyvera species. No additional peripheral blood cultures were obtained during this period. Throughout this time, the patient remained severely neutropenic (Table 1). She had virtually no neutrophils until hospital Day 15, when her white blood cell count rose to 1.51 X 109 and her ANG was 477.

On hospital Day 12, the patient's CVC site was again noted to be erythematous and mildly tender; therefore, the use of the CVC was discontinued. It is noteworthy that before this time, all antibiotics had been administered through the CVC. A blood culture obtained from the CVC on hospital Day 13 again grew Kluyvera species (Table 1). The patient's temperature reached a maximum of 100.1[degrees]F. Because of the recurrence of the Kluyvera species infection, the CVC was removed on hospital Day 14. The catheter tip was not cultured.

The patient became afebrile after the CVC was removed, and subsequent blood cultures obtained within 24 hours of removal of the CVC were negative for Kluyvera organisms. On hospital Day 16, the patient's ANC was greater than 1,000. She was then discharged to home to complete an additional 5 days of tobramycin therapy after CVC removal.

From the Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS.

Reprint requests to Tami Brooks, MD, Department of Pediatrics, University of Mississippi Medical Center, 2500 N. State Street,-Jackson, MS 39211.

Copyright [c] 2003 by The Southern Medical Association 0038-4345/03/9602-0214