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Table 1. 
Significant Difference Between Community-Acquired and Nosocomial Klebsiella pneumoniae Bacteremia Among Various Underlying Conditions*
Significant Difference Between Community-Acquired and Nosocomial Klebsiella pneumoniae Bacteremia Among Various Underlying Conditions*
Table 2. 
Significant Difference Between Community-Acquired and Nosocomial Klebsiella pneumoniae Bacteremia Among Predisposing Factor, Source of Infection, and Clinical Finding*
Significant Difference Between Community-Acquired and Nosocomial Klebsiella pneumoniae Bacteremia Among Predisposing Factor, Source of Infection, and Clinical Finding*
Table 3. 
Differences of the Antimicrobial Resistance for Klebsiella pneumoniae Bacteremic Isolates From Community-Acquired and Nosocomial Infections
Differences of the Antimicrobial Resistance for Klebsiella pneumoniae Bacteremic Isolates From Community-Acquired and Nosocomial Infections
Table 4. 
Significant Difference of Capsular Serotype in Bacteremic Klebsiella pneumoniae Isolates Between Community-Acquired and Nosocomial Infections
Significant Difference of Capsular Serotype in Bacteremic Klebsiella pneumoniae Isolates Between Community-Acquired and Nosocomial Infections
Table 5. 
Source of Infection and Capsular Serotype of Bacteremic Klebsiella pneumoniae Between Community-Acquired and Nosocomial Infections
Source of Infection and Capsular Serotype of Bacteremic Klebsiella pneumoniae Between Community-Acquired and Nosocomial Infections
Table 6. 
Significant Risk Factors for Mortality in Patients With Klebsiella pneumoniae Bacteremia*
Significant Risk Factors for Mortality in Patients With Klebsiella pneumoniae Bacteremia*
1.
Yinnon  AMButnaru  ARaveh  DJerassy  ZRudensky  B Klebsiella bacteraemia: community versus nosocomial infection. QJM. 1996;89933- 941Article
2.
Montgomerie  JZ Epidemiology of Klebsiella and hospital-associated infections. Rev Infect Dis. 1979;1736- 753Article
3.
Bryan  CSReynolds  KLBrenner  ER Analysis of 1186 episodes of gram-negative bacteremia in non-university hospitals: the effects of antimicrobial therapy. Rev Infect Dis. 1983;5629- 638Article
4.
Meyer  KSUrban  CEagan  JABerger  BJRahal  JJ Nosocomial outbreak of Klebsiella infection resistant to late-generation cephalosporins. Ann Intern Med. 1993;119353- 358Article
5.
Philippon  ALabia  RJacoby  G Extended-spectrum β-lactamases. Antimicrob Agents Chemother. 1989;331131- 1136Article
6.
Wang  LSLee  FYCheng  DLLiu  CYHinthorn  DRJost  PM Klebsiella pneumoniae bacteremia: analysis of 100 episodes. J Formos Med Assoc. 1990;89756- 763
7.
Domenico  PJohanson  WG  JrStraus  DC Lobar pneumonia in rats produced by clinical isolates of Klebsiella pneumoniae. Infect Immun. 1982;37327- 335
8.
Ehrenworth  LBaer  H The pathogenicity of Klebsiella pneumoniae for mice: the relationship to the quantity and rate of production of type-specific polysaccharide. J Bacteriol. 1956;72713- 717
9.
Martin  WJYu  PKWWashington  JA Epidemiological significance of Klebsiella pneumoniae: a 3-month study. Mayo Clin Proc. 1971;46785- 793
10.
Selden  RLee  SWang  WLLBennett  JVEickhoff  TC Nosocomial Klebsiella infections: intestinal colonization as a reservoir. Ann Intern Med. 1971;74657- 664Article
11.
Riser  ENoone  P Klebsiella capsular type versus site of isolations. J Clin Pathol. 1981;34552- 555Article
12.
Fung  CPHu  BSChang  FY  et al.  A 5-year study of the seroepidemiology of Klebsiella pneumoniae: high prevalence of capsular serotype K1 in Taiwan and implication for vaccine efficacy. J Infect Dis. 2000;1812075- 2079Article
13.
Cryz  SJ  JrMortimer  PMMansfield  VGermanier  R Seroepidemiology of Klebsiella bacteremic isolates and implications for vaccine development. J Clin Microbiol. 1986;23687- 690
14.
National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disk Susceptibility Tests: Approved Standard M2-A6.  Villanova, Pa National Committee for Clinical Laboratory Standards1997;
15.
Palfreyman  JM Klebsiella serotyping by counter-current immunoelectrophoresis. J Hyg (Lond). 1978;81219- 225Article
16.
Knaus  WAWagner  DPDraper  EA  et al.  The APACHE III prognostic system: risk prediction of hospital mortality for critically ill hospitalized adults. Chest. 1991;1001619- 1636Article
17.
Korvick  JABryan  CSFarber  B  et al.  Prospective observational study of Klebsiella bacteremia in 230 patients: outcome for antibiotic combinations versus monotherapy. Antimicrob Agents Chemother. 1992;362639- 2644Article
18.
Watanakunakorn  CJura  J Klebsiella bacteremia: a review of 196 episodes during a decade (1980-1989). Scand J Infect Dis. 1991;23399- 405Article
19.
Garcia de la Torres  MRomero-Vivas  JMartinez-Beltran  JGuerrero  AMeseguer  MBouza  E Klebsiella bacteremia: an analysis of 100 episodes. Rev Infect Dis. 1985;7143- 150Article
20.
Bodey  GPElting  LSRodriquez  SHernandez  M Klebsiella bacteremia: A 10-year review in a cancer institution. Cancer. 1989;642368- 2376Article
21.
Haddy  RILee  L  IIISangal  SPWalbroehl  GSHambrick  CSSanti  GM Klebsiella pneumoniae bacteremia in the community hospital. J Fam Pract. 1989;28686- 690
22.
Montgomerie  JZOta  JK Klebsiella bacteremia. Arch Intern Med. 1980;140525- 527Article
23.
Bonadio  WA Klebsiella pneumoniae bacteremia in children: fifty-seven cases in 10 years. AJDC. 1989;1431061- 1063
24.
Feldman  CSmith  CLevy  HGinsburg  PMiller  SDKoornhof  HJ Klebsiella pneumoniae bacteremia at an urban general hospital. J Infect. 1990;2021- 31Article
25.
Umsawasdi  TMiddleman  EALuna  MBodey  GP Klebsiella bacteremia in cancer patients. Am J Med Sci. 1973;265473- 482Article
26.
Lee  KHHui  KPTan  WCLim  TK Klebsiella bacteremia: a report of 101 cases from National University Hospital, Singapore. J Hosp Infect. 1994;27299- 305Article
27.
Chang  FYChou  MY Comparison of pyogenic liver abscesses caused by Klebsiella pneumoniae and non–K pneumoniae pathogens. J Formos Med Assoc. 1995;94232- 237
28.
Chang  FYChou  MYFan  RLShaio  MF A clinical study of Klebsiella liver abscess. Taiwan Yi Xue Hui Za Zhi. 1988;87282- 287
29.
Rose  HDSchrerer  J The effect of hospitalization and antibiotic therapy on the gram-negative fecal flora. Am J Med Sci. 1968;225228- 236Article
30.
Schiappa  DAHayden  MKMatushek  MG  et al.  Ceftazidime-resistant Klebsiella pneumoniae and Escherichea coli bloodstream infection: a case-control and molecular epidemiologic investigation. J Infect Dis. 1996;174529- 536Article
31.
Wang  JHLiu  YCLee  SS  et al.  Primary liver abscess due to Klebsiella pneumoniae in Taiwan. Clin Infect Dis. 1998;261434- 1438Article
32.
Liu  YCCheng  DLLin  CL Klebsiella pneumoniae liver abscess associated with septic endophthalmitis. Arch Intern Med. 1986;1461913- 1916Article
33.
Cheng  DLLiu  YCYen  MYLiu  CYWang  RS Septic metastatic lesions of pyogenic liver abscess. Arch Intern Med. 1991;1511557- 1559Article
34.
Mizuta  KOhta  MMori  MHasegawa  TNakashima  IKato  N Virulence for mice of Klebsiella strains belonging to O1 group: relationship to their capsular (K) types. Infect Immun. 1983;4056- 61
35.
Casewell  MTalsania  HG Predominance of certain Klebsiella capsular types in hospital in the United Kingdom. J Infect. 1979;177- 79Article
36.
Riser  ENoone  P Klebsiella capsular type versus site of isolation. J Clin Pathol. 1981;34552- 555Article
37.
Paterson  DLKo  WCVon Gottberg  A  et al.  Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum β-lactamases: implications for the clinical microbiology laboratory. J Clin Microbiol. 2001;392206- 2212Article
Original Investigation
May 13, 2002

Characteristics of Bacteremia Between Community-Acquired and Nosocomial Klebsiella pneumoniae InfectionRisk Factor for Mortality and the Impact of Capsular Serotypes as a Herald for Community-Acquired Infection

Author Affiliations

From the Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center (Drs Tsay and Chang), the Division of Clinical Research, National Health Research Institute (Dr Siu), and the Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University (Dr Fung), Taipei, Taiwan. Dr Tsay is now with the Division of Infectious Diseases, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.

Arch Intern Med. 2002;162(9):1021-1027. doi:10.1001/archinte.162.9.1021
Abstract

Background  Although several epidemiological surveys of Klebsiella clinical isolates have been performed, few studies have correlated the clinical isolate with disease.

Objective  To compare the clinical and bacteriological characteristics of Klebsiella pneumoniae bacteremia acquired as community or nosocomial infections.

Methods  We prospectively enrolled 158 consecutively hospitalized patients with K pneumoniae bacteremia. Clinical data were reviewed. Antimicrobial susceptibility testing and capsular serotyping were performed. We used the χ2 test, the Fisher exact test, or the t test for statistic analysis.

Results  Underlying diabetes mellitus was more common in community-acquired than in nosocomial infection (46/94 [49%] vs 8/64 [12%]; P<.001). On the other hand, neoplastic disease (34/64 [53%] vs 13/94 [14%]; P<.001) and antibiotic resistance (P<.01) were more frequent in patients with nosocomial compared with community-acquired infections. Klebsiella pneumoniae liver abscesses, which were all community acquired, accounted for the source of 22 (23%) of 94 community-acquired K pneumoniae infections. No attributable source of infection was found for 37 (58%) of the 64 nosocomial infections vs 15 (16%) of the 94 community-acquired infections. Only 58 isolates (36.7%) could be serotyped; of these, capsular serotypes K1, K2, and K28 accounted for 37 (23.4%), 8 (5.1%), and 6 (3.8%), respectively, of all strains. However, typeable isolates were significantly more common among community-acquired than nosocomial isolates (42/94 [45%] vs 16/64 [25%]; P = .01), especially for serotype K1 (28/94 [30%] vs 9/64 [14%]; P = .02). Significant risk factors for mortality included nosocomial infection, lung infection, thrombocytopenia, leukopenia, ceftazidime resistance, inappropriate antimicrobial therapy, and septic shock.

Conclusions  Significant differences were identified between community-acquired and nosocomial K pneumoniae bacteremia. Ceftazidime resistance in nosocomial K pneumoniae bacteremia carried a high risk for mortality, and serotype K1 in K pneumoniae was more prevalent in community-acquired infection, suggesting more virulence.

KLEBSIELLA PNEUMONIAE causes suppurative infections, bacteremia, and a substantial percentage of nosocomal infections. It is the second most common cause of gram-negative bacteremia.13 Strains of K pneumoniae that are resistant to multiple antibiotics, including the newer cephalosporins, have developed.4 Infections caused by these extended-spectrum β-lactamase–producing K pneumoniae are frequently epidemic in nature and have complicated chemotherapy significantly.46 Most clinical isolates of K pneumoniae possess a well-defined polysaccharide capsule that appears to be a critical virulence factor.7,8 Although several seroepidemiological surveys of Klebsiella clinical isolates have been performed,912 few studies have correlated the clinical isolate with disease.9,10 Some capsular serotypes are isolated at significantly higher frequency than others.12,13 We conducted this study to compare the clinical and bacteriological characteristics of K pneumoniae bacteremia acquired as community or nosocomial infection.

MATERIALS AND METHODS
DURATION OF STUDY

From April 1, 1997, through March 31, 1999, patients with a blood culture positive for K pneumoniae at the Tri-Service General Hospital, a 1300-bed university hospital in Taipei, Taiwan, were prospectively enrolled. The clinical features of these patients and the bacteriological characteristics of these K pneumoniae strains were collected and analyzed.

DEFINITIONS

Klebsiella pneumoniae bacteremia was defined as the isolation of K pneumoniae in 1 or more blood cultures in association with the clinical features of bacteremia and/or sepsis. Bacteremia was considered to be nosocomial if a blood culture that yielded positive findings was obtained later than 72 hours after admission, and if the bacteremia was not obviously associated with the clinical conditions of the patient at the time of admission. Otherwise, bacteremia was considered to be community acquired.

Previous corticosteroid treatment was defined as corticosteroid therapy for at least 2 weeks before the onset of the K pneumoniae bacteremia. Recent surgery was defined as a surgical procedure that had been performed within 1 month of the onset of K pneumoniae bacteremia. The source of bacteremia was defined clinically or by the isolation of K pneumoniae from the site of entry or both. An infiltrate had to be seen on the chest radiograph to substantiate the presence of pneumonia.

Shock was defined as a decrease in systolic blood pressure to a level of less than 90 mm Hg or a decrease of at least 40 mm Hg below baseline blood pressure, despite adequate fluid resuscitation, in conjunction with organ dysfunction and perfusion abnormalities (eg, lactic acidosis, oliguria, obtundation). Jaundice was defined as a total serum bilirubin level of at least 2.0 mg/dL (≥34.2 µmol/L).

Leukocytosis was defined as a white blood cell count of greater than 10 000/µL; leukopenia, a white blood cell count of less than 4000/µL; and thrombocytopenia, a platelet count of less than 100 000/µL.

ANTIMICROBIAL THERAPY

Antimicrobial therapy was considered to be appropriate if 1 or more antimicrobial agents were active in vitro against the corresponding isolate when the agent(s) was given at an adequate dosage via an appropriate route for at least 2 days within 3 days of obtaining a blood culture that yielded positive results. Mortality was considered to be related to bacteremia if the patient was being treated for bacteremia when death occurred, unless clinical and pathological data clearly suggested otherwise.

BACTERIAL ISOLATES AND ANTIMICROBIAL SUSCEPTIBILITY TESTING

All isolates were identified by means of the API 20E system (bioMérieux SA, Marcy I'Etoile, France). Antimicrobial susceptibilities were determined by means of the Kirby-Bauer disk-diffusion test on Mueller-Hinton agar (BBL Microbiologic System, Cockeysville, Md) for the following antibiotics: ampicillin (10 µg), amikacin (30 µg), aztreonam (30 µg), cefazolin (30 µg), cefuroxime (30 µg), ceftriaxone (30 µg), ceftazidime (30 µg), ciprofloxacin (30 µg), gentamicin (10 µg), imipenem (30 µg), piperacillin (100 µg), and a combination of trimethoprim and sulfamethoxazole (1.25 µg and 23.75 µg, respectively). Interpretations were performed according to the guidelines of the National Committee for Clinical Laboratory Standards.14

CAPSULAR SEROTYPE

The isolates were serotyped by means of the countercurrent immunoelectrophoresis method.15 Antisera were provided by the Laboratory of Hospital Infection, Central Public Health Laboratory, London, England. In brief, strains to be serotyped were grown overnight on MacConkey agar (Difco Laboratories, Detroit, Mich), and a light suspension of bacteria was resuspended in isotonic sodium chloride solution with different antisera. Each isolate was tested against 14 antiserum pools by means of countercurrent immunoelectrophoresis and then tested again with the specific antisera of the reacting pool. Isolates were examined by means of the quellung (capsular swelling) reaction with antisera if cross-reactions occurred or if equivocal results were obtained by means of countercurrent immunoelectrophoresis. Isolates that failed to react in both methods were considered nontypeable. Klebsiella pneumoniae ATCC 9997 (K2, where K indicates capsular serotype) was used as a control strain.

The severity of illness was evaluated by means of the APACHE III (Acute Physiology and Chronic Health Evaluation III) score system.16

STATISTICAL ANALYSIS

We performed statistical analysis using the χ2 test, the Fisher exact test, or the t test. When the P value was less than .05, the difference was considered statistically significant.

RESULTS
UNDERLYING CONDITIONS

During the 2-year study, 158 patients with an episode of K pneumoniae bacteremia were prospectively enrolled. Ninety-four episodes (59.5%) were community acquired, and 64 (40.5%) were nosocomial in origin (Table 1). The ages of patients ranged from 25 weeks to 90 years (mean ± SD age, 60 ± 19 years). The male-female ratio was 1.4:1.

The common underlying diseases associated with community-acquired K pneumoniae bacteremia were diabetes mellitus (n = 46 [49%]), hepatobiliary disease (n = 29 [31%]), and neoplastic diseases (n = 13 [14%]). The common underlying diseases associated with nosocomial K pneumoniae bacteremia were neoplastic diseases (n = 34 [53%]), hepatobiliary diseases (n = 14 [22%]), and diabetes mellitus (n = 8 [12%]). Underlying diabetes mellitus was more common in community-acquired than in nosocomial infection (49% vs 12%; P<.001). Neoplastic disease was more frequently noted in patients with nosocomial compared with community-acquired infection (53% vs 14%; P<.001; Table 1).

CLINICAL FEATURES AND TREATMENT OF THE ENROLLED PATIENTS

In the nosocomial K pneumoniae bacteremia group, 15 patients (23%) had indwelling urinary catheters or had undergone recent urinary manipulations. Eleven patients (17%) were receiving immunosuppressive therapy, including chemotherapy for neoplastic diseases (n = 9) and corticosteroid treatment (n = 2). Five of 11 patients with bacteremia who required respiratory assistance had pneumonia. Of the 37 patients with an unknown source of nosocomial bacteremia, 5 patients had a central venous catheter in place, 2 were receiving corticosteroid therapy, 6 were receiving chemotherapy, 2 had a central venous catheter and had undergone recent abdominal surgery, and 1 had undergone recent abdominal surgery. All of these predisposing factors were found more frequently in patients with nosocomial bacteremia (P = .01; Table 2).

For infection origin, intra-abdominal (P<.001) and urinary tract (P = .01) infections were significantly higher in community-acquired bacteremia. On the contrary, patients with an unknown origin of infection had a significantly higher incidence of nosocomial than community-acquired bacteremia (P<.001; Table 2).

Shock developed in 34 (21.5%) of 158 patients. Twenty patients (12.7%) displayed leukopenia. Of these, 10 (50.0%) had received chemotherapy for underlying hematologic neoplasms. Of the patients with leukopenia, 2 had undergone radiotherapy, 4 had cirrhosis of liver, 1 had aplastic anemia, and 3 had no underlying condition. One hundred eight patients (68.4%) showed leukocytosis. Sixty patients (38.0%) showed thrombocytopenia. Thirty patients (19.0%) had jaundice. The APACHE III score was higher in patients with nosocomial infections compared with those with community-acquired K pneumoniae bacteremia (mean ± SD score, 41 ± 24 vs 33 ± 21; P = .03). The overall mortality rate was 22.8% (36/158 patients). The mortality rate was higher in patients with nosocomial infections compared with those with community-acquired infections (36% vs 14%; P = .001) (Table 2). No significant differences between community-acquired and nosocomial bacteremia were observed in corticosteroid use, lung infection, leukocytosis, thrombocytopenia, creatinine levels of at least 2 mg/dL (≥176.8 µmol/L), ceftazidime resistance, inappropriate antibiotic therapy, metastatic foci, and shock.

PATIENTS WITH POLYMICROBIAL INFECTION AND ANTIMICROBIAL SUSCEPTIBILITY TESTING

Of the 158 patients, 21 (13.3%) were identified as having polymicrobial bacteremia. The concomitant organisms were Enterococcus (n = 7), Enterobacter cloacae (n = 4), Proteus mirabilis (n = 3), Escherichia coli (n = 3), methicillin-sensitive Staphylococcus aureus (n = 2), Pseudomonas aeruginosa (n = 1), Serratia marcescens (n = 1), Bacteroides species (n = 1), Streptococcus pneumoniae (n = 1), Enterobacter gergoviae (n = 1), and Citrobacter freundii (n = 1). The underlying disease in these patients included malignancies (n = 8 [38%]), cholangitis complicating hepatobiliary calculus (n = 5 [24%]), and urinary tract infection in debilitated conditions (n = 5 [24%]). In these patients with polymicrobial infections, the 8 patients with malignancy acquired the infection in the hospital, whereas the 5 patients with urinary tract infection acquired it in the community.

The antimicrobial susceptibility of the bacteremic isolates of K pneumoniae is shown in Table 3. Community-acquired isolates showed the highest frequency of resistance to trimethoprim-sulfamethoxazole (n = 22 [23%]), followed by piperacillin (n = 16 [17%]), cefazolin (n = 13 [14%]), and gentamicin (n = 10 [11%]). Resistance to third-generation cephalosporins was low (<5%). Among hospital-acquired isolates, resistance to trimethoprim sulfamethoxazole or piperacillin was most common (n = 28 [44%]), followed by cefazolin (n = 23 [36%]), gentamicin (n = 18 [28%]), cefuroxime (n = 16 [25%]), aztreonam (n = 16 [25%]), and amikacin (n = 11 [17%]). Resistance to ceftazidime and ceftriaxone was found in 14 (22%) and 11 patients (17%), respectively. The resistance of hospital-acquired isolates was significantly higher than that of the community-acquired isolates (P<.005), except imipenem. Nosocomial isolates also had a higher overall frequency of resistance to multiple antibiotics.

SEROTYPING AND CORRELATION AMONG DIFFERENT INFECTIOUS SITES

Of the 158 strains of K pneumoniae, 58 (36.7%) could be serotyped, and 9 different serotypes were identified (Table 4). The most common were serotypes K1, K2, and K28, and these accounted for 37 (23.4%), 8 (5.1%), and 6 (3.8%) strains, respectively (Table 4). Typeable isolates were significantly more common among the community-acquired isolates than among nosocomial isolates (42/94 [45%] vs 16/64 [25%]; P = .01). Isolation of the K1 serotype in community-acquired infection was significantly higher than in nosocomial infection (28/94 [30%] vs 9/64 [14%]; P = .02). On the contrary, nontypeable K pneumoniae was significantly higher in nosocomial infection (48/64 [75%] vs 52/94 [55%]; P = .01; Table 4).

The sources of infection and capsular serotypes of K pneumoniae are shown in Table 5. Most of the bacteremic K pneumoniae isolates were of a nontypeable serotype when the infection source was the lung, the urinary tract, or unknown. In contrast, most of the K pneumoniae isolates had an identifiable serotype when the infection source was in the abdomen. This higher rate of typeable isolates for intra-abdominal infection compared with other sources of infection was statistically significant (P = .001). Klebsiella pneumoniae liver abscesses, which were all community acquired, accounted for 23% of the source of community-acquired K pneumoniae bacteremia. Infection caused by serotypes K1 and K2 was statistically significantly higher in liver abscess compared with other sources of infection (P = .02). Serotype K1 isolate from unknown infection sources was more common in the community-acquired infections than in the nosocomial infections at a statistically significant level (7/15 [47%] vs 4/37 [11%]; P = .02). The presence of serotype K1 isolates, however, was not correlated with the presence of underlying diabetes mellitus.

RISK FACTOR FOR MORTALITY

Nosocomial bacteremia, ceftazidime resistance, leukopenia, and higher APACHE III scores were identified as risk factors for higher mortality (P<.005; Table 6). Although no significant difference between community-acquired and nosocomial bacteremia were observed in lung infection, thrombocytopenia, inappropriate antibiotic therapy, and septic shock, these variables were all identified as risk factors associated with significantly higher mortality (P<.05; Table 6).

COMMENT

Most of the patients in this study were elderly (mean ± SD age, 60 ± 19 years), with a slight male predominance (59%) in the group. The rate of hospital-acquired K pneumoniae bacteremia was 40.5%, which was lower than in studies during the past 28 years,1,6,1725 except for a study from Singapore.26

Diabetes mellitus was the most commonly associated condition in patients with community-acquired K pneumoniae bacteremia, and the percentage of patients with diabetes (49%) was higher than in previous studies.1,6,1726 The association of diabetes mellitus and K pneumoniae liver abscess in Taiwan was reported previously in studies from our institution.27,28 Neoplastic diseases (53%) were the most commonly associated condition in patients with nosocomial K pneumoniae bacteremia. Longer hospitalization, invasive procedures, chemotherapy, and the use of antibiotics are common in patients with neoplastic diseases. A higher rate of fecal colonization by K pneumoniae has been noted in patients with neoplastic diseases than in control subjects, and this has been associated with antibiotic use.29

Fever occurred at a statistically significant lower rate in patients with nosocomial bacteremia than those with community-acquired bacteremia (53/64 [83%] vs 88/94 [94%]; P = .03). A higher percentage of neoplastic diseases, uremia, and corticosteroid use in patients with nosocomial bacteremia may be responsible. There was a higher percentage of leukopenia in nosocomial vs community-acquired bacteremia (14/64 [22%] vs 6/94 [6%]; P = .004), and this could have been due to a higher rate of chemotherapy for neoplastic diseases in the patients with nosocomial bacteremia. Thrombocytopenia, leukocytosis, shock, and polymicrobial causes were not significantly different between nosocomial and community-acquired bacteremia.

The nosocomial isolates were significantly more resistant to the antimicrobial agents that were tested, except for imipenem, when compared with the community-acquired isolates. More than 20% of the nosocomial strains were resistant to one of the third-generation cephalosporins, which raises a concern over an increasing prevalence of extended-spectrum β-lactamase (ESBL)–producing K pneumoniae, particularly in hospitals. The ESBL-producing K pneumoniae infections are a risk factor associated with treatment failure30; therefore, aggressive infection control, including isolation of patients infected with ESBL-producing K pneumoniae and the imposition of restrictions on the use of third-generation cephalosporin, should be implemented.

A source of infection was identifiable in 67.1% of cases. The most common source was a urinary tract infection (20.9%), followed by liver abscess (13.9%). This finding is similar to those of a study performed in Singapore,25 but has not been reported elsewhere for other Klebsiella bacteremia studies. In our study, of the 22 patients with liver abscess, a metastatic infection developed in 3 (one had endophthalmitis, a brain abscess, and septic pulmonary emboli; endophthalmitis developed in another; and the last one had meningitis). Metastatic infection is a characteristic feature of K pneumoniae liver abscesses in Taiwan.27,3133 Bacteremia with an unknown source of infection was more commonly associated with nosocomial than with community-acquired infections (58% vs 16%; P<.001). Many patients in whom nosocomial bacteremia develops have been subjected to invasive procedures such as urinary catheterization or manipulation, respiratory assistance, central venous catheterization, and recent surgery, which suggests that the procedure itself may be responsible for the bacteremia.

The seroepidemiology of Klebsiella infection has been explored in a number of studies, but none of them have clearly identified a relationship between the capsular serotype and specific clinical diseases. The aim of the present study was to correlate the relationship between the capsular serotype of bacteremic K pneumoniae and the source of infection. We found that serotypes K1 and K2 were common in isolates from patients with abdominal infections, such as liver abscesses, and with community-acquired infections from an unknown source. Klebsiella pneumoniae liver abscess is a well-known disease in Taiwan that presents as a serious infectious complication in patients with diabetes.28 For nosocomial infections, nontypeable isolates were predominant when the source of infection was identified as the lung, the urinary tract, or an unknown source.

Of the 158 strains of K pneumoniae, 58 (36.7%) could be serotyped, and 9 different serotypes were identified. This differed from previous reports in which more than 90% of the isolates have been typeable and the distribution of the serotypes was very wide.9,13 In Europe and North America, serotypes K2, K21, and K55 (accounting for 8.9%, 7.8% and 4.8%, respectively), made up 21.5% of all isolates, and this was significantly higher than the remaining serotypes in K pneumoniae bacteremic isolates. In contrast, we found serotypes K1, K2, and K28 accounted for 37 (23.4%), 8 (5.1%), and 6 (3.8%), respectively, of all strains in this study.

Of the typeable community-acquired bacteremic isolates (n = 42), 34 (81%) were serotypes K1 and K2, especially with an intra-abdominal infection or an unknown source of infection. Of nosocomial bacteremic isolates, nontypeable serotypes predominated (48/64 [75%]). Serotypes K1 and K2 have been described as the predominant typeable serotype in Taiwan.12 Serotypes K1 and K2 showed more virulence than other serotypes in mice.34 However, nontypeable capsular serotypes may possess an epidemiological advantage compared with other strains, and this may enable them to colonize and infect hospital patients more easily.35,36 Nontypeable serotypes accounted for most of the bacteremic isolates where the urinary tract or a lung was identified as an infection source. Serotypes K1 and K2 were significantly more common in patients in whom the source of infection was liver abscess (11 of 22) than in those with other sources of infection (P = .02). For all patients with liver abscesses who developed complications involving metastatic foci, their disease was attributable to serotype K1 isolates. Whether a specific bacterial strain of K pneumoniae is associated with liver abscesses or whether other factors such as race, environment, or the presence of diabetes mellitus are involved requires further clarification. The high proportion of nontypeable strains in the study also requires further investigation.

The overall mortality in our series was 22.8%. The reported mortalities in Klebsiella bacteremia range from 20% to 62%.1,6,1726 In the present study, risk factors for mortality in patients with K pneumoniae bacteremia included nosocomial infection, lung infection, thrombocytopenia, leukopenia, infection with ceftazidime-resistant isolates, inappropriate antimicrobial therapy, and septic shock. In contrast to previous studies,18,24 an increase in serum creatinine or total serum bilirubin level at the onset of bacteremia was not associated significantly with a higher mortality rate. We could not detect any statistically significant difference for mortality between any typeable serotype and the nontypeable serotypes.

CONCLUSIONS

Klebsiella pneumoniae bacteremia is a very important cause of morbidity and mortality in gram-negative bacteremia in Taiwan, and this is similar to the situation in most medically well-developed countries. Urinary tract infection and liver abscess were the most common infection sources for K pneumoniae bacteremia. Diabetes mellitus, neoplastic diseases, and hepatobiliary diseases were the most common underlying conditions. Of all community-acquired and nosocomial isolates, 2% and 22%, respectively, were ceftazidime resistant. Thus, strict control of the use of third-generation cephalosporins and other antibiotics should be instituted in the community and in the hospital.37 Only 36.7% of K pneumoniae bacteremia isolates could be serotyped; of these, 45 (78%) were serotypes K1 and K2. This study shows a significantly higher prevalence of K1 in bacteremic K pneumoniae isolate in Taiwan, especially in patients with an infection source identified as liver abscess, biliary tract infection, or unknown. Of the nosocomial bacteremic isolates, a nontypeable serotype was predominant in 48 (75%). Further study on the capsular serotype and the virulence of the K pneumoniae is warranted. The mortality rate remains high, despite proper antimicrobial treatment and supportive measures. Factors indicating poor prognosis include the presence of a nosocomial infection, a lung infection, thrombocytopenia, leukopenia, the presence of a ceftazidime-resistant isolate, the application of an inappropriate antimicrobial therapy, and septic shock.

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Article Information

Accepted for publication September 6, 2001.

This study was partly supported by grant TSGH-C88-09 from Tri-Service General Hospital and a grant from the National Health Research Institute, Taipei, Taiwan.

We thank Monto Ho, MD, for his critical review of the report.

Corresponding author and reprints: Feng-Yee Chang, MD, PhD, Division of Infectious Diseases and Tropical Medicine, Tri-Service General Hospital, No. 325, Section 2, Cheng-Kung Road, Neihu, 114 Taipei, Taiwan (e-mail: fychang@ndmctsgh.edu.tw).

References
1.
Yinnon  AMButnaru  ARaveh  DJerassy  ZRudensky  B Klebsiella bacteraemia: community versus nosocomial infection. QJM. 1996;89933- 941Article
2.
Montgomerie  JZ Epidemiology of Klebsiella and hospital-associated infections. Rev Infect Dis. 1979;1736- 753Article
3.
Bryan  CSReynolds  KLBrenner  ER Analysis of 1186 episodes of gram-negative bacteremia in non-university hospitals: the effects of antimicrobial therapy. Rev Infect Dis. 1983;5629- 638Article
4.
Meyer  KSUrban  CEagan  JABerger  BJRahal  JJ Nosocomial outbreak of Klebsiella infection resistant to late-generation cephalosporins. Ann Intern Med. 1993;119353- 358Article
5.
Philippon  ALabia  RJacoby  G Extended-spectrum β-lactamases. Antimicrob Agents Chemother. 1989;331131- 1136Article
6.
Wang  LSLee  FYCheng  DLLiu  CYHinthorn  DRJost  PM Klebsiella pneumoniae bacteremia: analysis of 100 episodes. J Formos Med Assoc. 1990;89756- 763
7.
Domenico  PJohanson  WG  JrStraus  DC Lobar pneumonia in rats produced by clinical isolates of Klebsiella pneumoniae. Infect Immun. 1982;37327- 335
8.
Ehrenworth  LBaer  H The pathogenicity of Klebsiella pneumoniae for mice: the relationship to the quantity and rate of production of type-specific polysaccharide. J Bacteriol. 1956;72713- 717
9.
Martin  WJYu  PKWWashington  JA Epidemiological significance of Klebsiella pneumoniae: a 3-month study. Mayo Clin Proc. 1971;46785- 793
10.
Selden  RLee  SWang  WLLBennett  JVEickhoff  TC Nosocomial Klebsiella infections: intestinal colonization as a reservoir. Ann Intern Med. 1971;74657- 664Article
11.
Riser  ENoone  P Klebsiella capsular type versus site of isolations. J Clin Pathol. 1981;34552- 555Article
12.
Fung  CPHu  BSChang  FY  et al.  A 5-year study of the seroepidemiology of Klebsiella pneumoniae: high prevalence of capsular serotype K1 in Taiwan and implication for vaccine efficacy. J Infect Dis. 2000;1812075- 2079Article
13.
Cryz  SJ  JrMortimer  PMMansfield  VGermanier  R Seroepidemiology of Klebsiella bacteremic isolates and implications for vaccine development. J Clin Microbiol. 1986;23687- 690
14.
National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disk Susceptibility Tests: Approved Standard M2-A6.  Villanova, Pa National Committee for Clinical Laboratory Standards1997;
15.
Palfreyman  JM Klebsiella serotyping by counter-current immunoelectrophoresis. J Hyg (Lond). 1978;81219- 225Article
16.
Knaus  WAWagner  DPDraper  EA  et al.  The APACHE III prognostic system: risk prediction of hospital mortality for critically ill hospitalized adults. Chest. 1991;1001619- 1636Article
17.
Korvick  JABryan  CSFarber  B  et al.  Prospective observational study of Klebsiella bacteremia in 230 patients: outcome for antibiotic combinations versus monotherapy. Antimicrob Agents Chemother. 1992;362639- 2644Article
18.
Watanakunakorn  CJura  J Klebsiella bacteremia: a review of 196 episodes during a decade (1980-1989). Scand J Infect Dis. 1991;23399- 405Article
19.
Garcia de la Torres  MRomero-Vivas  JMartinez-Beltran  JGuerrero  AMeseguer  MBouza  E Klebsiella bacteremia: an analysis of 100 episodes. Rev Infect Dis. 1985;7143- 150Article
20.
Bodey  GPElting  LSRodriquez  SHernandez  M Klebsiella bacteremia: A 10-year review in a cancer institution. Cancer. 1989;642368- 2376Article
21.
Haddy  RILee  L  IIISangal  SPWalbroehl  GSHambrick  CSSanti  GM Klebsiella pneumoniae bacteremia in the community hospital. J Fam Pract. 1989;28686- 690
22.
Montgomerie  JZOta  JK Klebsiella bacteremia. Arch Intern Med. 1980;140525- 527Article
23.
Bonadio  WA Klebsiella pneumoniae bacteremia in children: fifty-seven cases in 10 years. AJDC. 1989;1431061- 1063
24.
Feldman  CSmith  CLevy  HGinsburg  PMiller  SDKoornhof  HJ Klebsiella pneumoniae bacteremia at an urban general hospital. J Infect. 1990;2021- 31Article
25.
Umsawasdi  TMiddleman  EALuna  MBodey  GP Klebsiella bacteremia in cancer patients. Am J Med Sci. 1973;265473- 482Article
26.
Lee  KHHui  KPTan  WCLim  TK Klebsiella bacteremia: a report of 101 cases from National University Hospital, Singapore. J Hosp Infect. 1994;27299- 305Article
27.
Chang  FYChou  MY Comparison of pyogenic liver abscesses caused by Klebsiella pneumoniae and non–K pneumoniae pathogens. J Formos Med Assoc. 1995;94232- 237
28.
Chang  FYChou  MYFan  RLShaio  MF A clinical study of Klebsiella liver abscess. Taiwan Yi Xue Hui Za Zhi. 1988;87282- 287
29.
Rose  HDSchrerer  J The effect of hospitalization and antibiotic therapy on the gram-negative fecal flora. Am J Med Sci. 1968;225228- 236Article
30.
Schiappa  DAHayden  MKMatushek  MG  et al.  Ceftazidime-resistant Klebsiella pneumoniae and Escherichea coli bloodstream infection: a case-control and molecular epidemiologic investigation. J Infect Dis. 1996;174529- 536Article
31.
Wang  JHLiu  YCLee  SS  et al.  Primary liver abscess due to Klebsiella pneumoniae in Taiwan. Clin Infect Dis. 1998;261434- 1438Article
32.
Liu  YCCheng  DLLin  CL Klebsiella pneumoniae liver abscess associated with septic endophthalmitis. Arch Intern Med. 1986;1461913- 1916Article
33.
Cheng  DLLiu  YCYen  MYLiu  CYWang  RS Septic metastatic lesions of pyogenic liver abscess. Arch Intern Med. 1991;1511557- 1559Article
34.
Mizuta  KOhta  MMori  MHasegawa  TNakashima  IKato  N Virulence for mice of Klebsiella strains belonging to O1 group: relationship to their capsular (K) types. Infect Immun. 1983;4056- 61
35.
Casewell  MTalsania  HG Predominance of certain Klebsiella capsular types in hospital in the United Kingdom. J Infect. 1979;177- 79Article
36.
Riser  ENoone  P Klebsiella capsular type versus site of isolation. J Clin Pathol. 1981;34552- 555Article
37.
Paterson  DLKo  WCVon Gottberg  A  et al.  Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum β-lactamases: implications for the clinical microbiology laboratory. J Clin Microbiol. 2001;392206- 2212Article
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