Kang-Won Choe

Bloodstream Infections Caused by Antibiotic-Resistant Gram-Negative Bacilli: Risk Factors for Mortality and Impact of Inappropriate Initial Antimicrobial Therapy on Outcome

ABSTRACT The marked increase in the incidence of infections due to antibiotic-resistant gram-negative bacilli in recent years is of great concern, as patients infected by those isolates might initially receive antibiotics that are inactive against the responsible pathogens. To evaluate the effect of inappropriate initial antimicrobial therapy on survival, a total of 286 patients with antibiotic-resistant gram-negative bacteremia, 61 patients with Escherichia coli bacteremia, 65 with Klebsiella pneumoniae bacteremia, 74 with Pseudomonas aeruginosa bacteremia, and 86 with Enterobacter bacteremia, were analyzed retrospectively. If a patient received at least one antimicrobial agent to which the causative microorganisms were susceptible within 24 h of blood culture collection, the initial antimicrobial therapy was considered to have been appropriate. High-risk sources of bacteremia were defined as the lung, peritoneum, or an unknown source. The main outcome measure was 30-day mortality. Of the 286 patients, 135 (47.2%) received appropriate initial empirical antimicrobial therapy, and the remaining 151 (52.8%) patients received inappropriate therapy. The adequately treated group had a 27.4% mortality rate, whereas the inadequately treated group had a 38.4% mortality rate (P = 0.049). Multivariate analysis showed that the significant independent risk factors of mortality were presentation with septic shock, a high-risk source of bacteremia, P. aeruginosa infection, and an increasing APACHE II score. In the subgroup of patients (n = 132) with a high-risk source of bacteremia, inappropriate initial antimicrobial therapy was independently associated with increased mortality (odds ratio, 3.64; 95% confidence interval, 1.13 to 11.72; P = 0.030). Our data suggest that inappropriate initial antimicrobial therapy is associated with adverse outcome in antibiotic-resistant gram-negative bacteremia, particularly in patients with a high-risk source of bacteremia.

Pseudomonas aeruginosa Bacteremia: Risk Factors for Mortality and Influence of Delayed Receipt of Effective Antimicrobial Therapy on Clinical Outcome

Among the nosocomial pathogens, Pseudomonas aeruginosa is recognized as a major cause of morbidity and mortality. Data on 136 patients with P. aeruginosa bacteremia were retrospectively analyzed to evaluate risk factors for mortality. The median age of the patients was 55 years (range, 15-85 years), 78.7% of the cases were hospital-acquired, and the 30-day mortality rate was 39% (53 of 136 patients). Multivariate analysis demonstrated that risk factors for mortality included severe sepsis, pneumonia, delay in starting effective antimicrobial therapy, and an increasing APACHE II score (all P values <.05). In 123 of the 136 patients (excluding 13 patients treated with inadequate definitive antibiotics), 30-day mortality was 27.7% (13 of 47 patients) in the group of patients who received initially effective empirical antimicrobial therapy, and 43.4% (33 of 76) in the group of patients who received delayed effective antimicrobial therapy (P=.079). There was a trend toward higher mortality as the length of delay increased. Delay in starting effective antimicrobial therapy for P. aeruginosa bacteremia tended to be associated with higher mortality.

Bloodstream Infections Due to Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae: Risk Factors for Mortality and Treatment Outcome, with Special Emphasis on Antimicrobial Therapy

ABSTRACT This study was conducted to evaluate risk factors for mortality and treatment outcome of bloodstream infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK). ESBL production in stored K. pneumoniae and E. coli blood isolates from Jan 1998 to Dec 2002 was phenotypically determined according to NCCLS guidelines and/or the double-disk synergy test. A total of 133 patients with ESBL-EK bacteremia, including 66 patients with ESBL-producing K. pneumoniae and 67 with ESBL-producing E. coli, were enrolled. The overall 30-day mortality rate was 25.6% (34 of 133). Independent risk factors for mortality were severe sepsis, peritonitis, neutropenia, increasing Acute Physiology and Chronic Health Evaluation II score, and administration of broad-spectrum cephalosporin as definitive antimicrobial therapy (P < 0.05 for each of these risk factors). In 117 of the 133 patients, excluding 16 patients who died within 3 days after blood culture sample acquisition, the 30-day mortality rates according to definitive antibiotics were as follows: carbapenem, 12.9% (8 of 62); ciprofloxacin, 10.3% (3 of 29); and others, such as cephalosporin or an aminoglycoside, 26.9% (7 of 26). When patients who received appropriate definitive antibiotics, such as carbapenem or ciprofloxacin, were evaluated, mortality in patients receiving inappropriate empirical antimicrobial therapy was found not to be significantly higher than mortality in those receiving appropriate empirical antimicrobial therapy (18.9 versus 15.5%; P = 0.666). Carbapenem and ciprofloxacin were the most effective antibiotics in antimicrobial therapy for ESBL-EK bacteremia. A delay in appropriate definitive antimicrobial therapy was not associated with higher mortality if antimicrobial therapy was adjusted appropriately according to the susceptibility results. Our data suggest that more prudent use of carbapenem as empirical antibiotic may be reasonable.

Outcome of Vancomycin Treatment in Patients with Methicillin-Susceptible Staphylococcus aureus Bacteremia

ABSTRACT Limited data on the clinical outcome of vancomycin treatment compared with that of beta-lactam treatment in patients with methicillin-susceptible Staphylococcus aureus bacteremia (MSSA-B) are available. We used different and complementary approaches: (i) a retrospective cohort study using a propensity score to adjust for confounding by treatment assignment and (ii) a matched case-control study. Of all patients with S. aureus bacteremia (SAB) in two university-affiliated hospitals over a 7-year period, 294 patients with MSSA-B were enrolled in the cohort study. The cases for the case-control study were defined as patients who received vancomycin treatment for MSSA-B; the controls, who were patients that received beta-lactam treatment for MSSA-B, were selected at a 1:2 (case:control) ratio according to the objective matching scoring system and the propensity score system. In the cohort study, SAB-related mortality in patients with vancomycin treatment (37%, 10/27) was significantly higher than that in those with beta-lactam treatment (18%, 47/267) (P = 0.02). In addition, multivariate analysis revealed that vancomycin treatment was associated with SAB-related mortality when independent predictors for SAB-related mortality and propensity score were considered (adjusted odds ratio of 3.3, 95% confidence interval of 1.2 to 9.5). In the case-control study using the objective matching scoring system and the propensity score system, SAB-related mortality in case patients was 37% (10/27) and in control patients 11% (6/54) (P < 0.01). Our data suggest that vancomycin is inferior to beta-lactam in the treatment of MSSA-B.

Outcome of Staphylococcus aureus Bacteremia in Patients with Eradicable Foci versus Noneradicable Foci

To determine the outcome of Staphylococcus aureus bacteremia (SAB) on mortality, including the impact of methicillin resistance and an initial delay (< or =48 h) of appropriate antibiotics, a retrospective cohort study including 238 patients with SAB was performed. By logistic regression, noneradicable or noneradicated foci, underlying cirrhosis, and cancer were found to be independent predictors of mortality. In patients with eradicable foci, there were no significant differences in the associated mortality rate between methicillin-resistant SAB (11%) and methicillin-susceptible SAB (13%), and between inappropriate (13%) and appropriate (10%) empirical therapy, respectively (P=.79 and P=.78, respectively). By logistic regression, it was found that, in the subgroup of patients with noneradicable foci, underlying cirrhosis (odds ratio [OR], 3.1) and methicillin-resistant SAB (OR, 2.4) were independently associated with mortality.

Evidence of Two Distinct Subsubtypes within the HIV-1 Subtype A Radiation

Members of HIV-1 group M are responsible for the vast majority of AIDS cases worldwide and have been classified on the basis of their phylogenetic relationships into nine roughly equidistant clades, termed subtypes. Although there are no known phenotypic correlates for these genotypes, the disproportionate spread of certain of these lineages has been taken to indicate that subtype-specific biological differences may exist. The subtype nomenclature thus remains an important molecular epidemiological tool with which to track the course of the group M pandemic. In this study, we have characterized HIV-1 strains described previously as unusual subtype A variants on the basis of partial sequence analysis. Six such strains from Cyprus (CY), South Korea (KR), and the Democratic Republic of Congo (CD) were PCR amplified from infected cell culture or patient PBMC DNA, cloned, and sequences in their entirety (94CY017, 97KR004, 97CDKTB48, and 97CDKP58) or as half genomes (97CDKS10 and 97CDKFE4). Distance and phylogenetic analyses showed that four of these viruses (94CY017, 97CDKTB48, 97CDKFE4, and 97CDKS10) were closely related to each other, but quite divergent from all other HIV-1 strains, except for subtype A viruses, which represented their closest relatives. In phylogenetic trees from gag, pol, env, and nef regions, the four newly characterized HIV-1 strains formed a distinct sister clade to subtype A, which was as closely related to subtype A as subsubtypes F1 and F2 are to each other. According to current nomenclature rules, this defines a subsubtype, which we have tentatively termed A2. The two other viruses, 97KR004 and 97CDKP58, as well as a full-length HIV-1 sequence from the sequence database (ZAM184), were found to represent complex A2/D, A2/G, and A2/C recombinants, respectively. These results indicate that HIV-1 subtype A is composed of two subsubtypes (A1 and A2), both of which appear to have a widespread geographic distribution. The A2 viruses described here represent the first reference reagents for this new group M lineage.

Diagnostic usefulness of a T-cell-based assay for extrapulmonary tuberculosis in immunocompromised patients

BACKGROUNDnThe low reactivity of the tuberculin skin test limits its clinical use in immunocompromised patients with extrapulmonary tuberculosis. A recently developed T-cell-based assay for diagnosing tuberculosis infection gave promising results. However, there were few data on the usefulness of this assay for diagnosing extrapulmonary tuberculosis in immunocompromised patients.nnnMETHODSnAll adult patients with suspected extrapulmonary tuberculosis were prospectively enrolled at 2 university-affiliated hospitals over an 18-month period. In addition to the conventional tests for diagnosing extrapulmonary tuberculosis, enzyme-linked immunospot (ELISPOT) assay for the interferon-gamma-producing T-cell response to early secretory antigenic target-6 and culture filtrate protein-10 was performed. The final diagnoses in patients with suspected extrapulmonary tuberculosis were classified by clinical category.nnnRESULTSnThere were 179 patients with suspected extrapulmonary tuberculosis enrolled: 59 (33%) were classified as immunocompromised. Of the 179 patients, 75 (42%) were classified as extrapulmonary tuberculosis, including 56 confirmed tuberculosis plus 19 probable tuberculosis, and 97 (54%) were classified as not tuberculosis. The remaining 7 (4%) had possible tuberculosis and were excluded from the final analysis. The tuberculin skin test (induration size >or=10 mm) was less sensitive in immunocompromised patients (38%; 95% confidence interval [CI], 19%-59%) than in immunocompetent patients (69%; 95% CI, 54%-81%, P=.01). In contrast, the ELISPOT assay retained a high sensitivity: (88%; 95% CI, 68%-97%) in immunocompromised patients compared with 96% (95% CI, 87%-100%) in immunocompetent patients (P=.32).nnnCONCLUSIONnThe immunosuppressive condition does not affect the diagnostic sensitivity of the ELISPOT assay for extrapulmonary tuberculosis.

Spectrum of Opportunistic Infections and Malignancies in Patients with Human Immunodeficiency Virus Infection in South Korea

To determine the frequency and types of major opportunistic diseases in patients with HIV infection in South Korea, we reviewed the medical records of 173 HIV-infected patients. The patients were seen from 1985 to 1998 at a referral hospital for AIDS in South Korea. Most patients (85%) were male, and 107 (62%) were infected by heterosexual contacts. CD4+ lymphocyte counts at presentation were <200/microL in 27% of the patients. Tuberculosis was the most frequent opportunistic infection (25% of patients), followed by candidiasis (21%), herpes zoster (20%), Pneumocystis carinii pneumonia (10%), cytomegalovirus disease (9.8%). There were no cases of toxoplasmosis. Kaposis sarcoma developed in 3 patients (1.7%), and non-Hodgkins lymphoma, in 2 (1.2%). Eleven patients (6.4%) developed peripheral neuropathy, and 8 (4.6%) had HIV encephalopathy. Tuberculosis was the single most important HIV-related infection in South Korean patients.

Bloodstream infections caused by Enterobacter species: predictors of 30-day mortality rate and impact of broad-spectrum cephalosporin resistance on outcome.

BACKGROUNDnEnterobacter species have become increasingly important nosocomial pathogens. However, resistance to cephalosporins often complicates the treatment of Enterobacter infection. This study was conducted to evaluate the predictors of mortality and the impact of cephalosporin resistance on outcome in patients with Enterobacter bacteremia.nnnMETHODSnA total of 183 patients with Enterobacter bacteremia were retrospectively analyzed. Broad-spectrum cephalosporin resistance was defined as in vitro resistance to cefotaxime or ceftazidime. The main outcome measure was the 30-day mortality rate.nnnRESULTSnOf 183 patients, 86 (47%) had bacteremia caused by broad-spectrum cephalosporin-resistant Enterobacter species, and their infections were classified as resistant. The 30-day mortality rate of patients with resistant infections (the resistant group) was significantly higher than that of patients with susceptible infections (the susceptible group) (33.7% vs. 18.6%; P=.021). When the 30-day mortality rates were compared according to the primary sites of infection and underlying conditions, the 30-day mortality rates of the resistant group were significantly higher than those of the susceptible group, in patients with an unknown primary site of infection, or in patients with septic shock. Multivariate analysis showed that broad-spectrum cephalosporin resistance was one of the independent risk factors associated with 30-day mortality (odds ratio [OR], 3.69; 95% confidence interval [CI], 1.01-13.52; P=.049). Presentation with septic shock and an increasing Acute Physiology and Chronic Health Evaluation II score were also independent risk factors for mortality (OR, 59.91 [95% CI, 14.93-240.15; P<.001] and 1.52 [95% CI, 1.24-1.86; P<.001], respectively).nnnCONCLUSIONSnBroad-spectrum cephalosporin resistance adversely affects the outcome of patients with Enterobacter bacteremia, especially those with an unknown primary site of infection and those with septic shock.

Diagnosis of central nervous system tuberculosis by T-cell-based assays on peripheral blood and cerebrospinal fluid mononuclear cells.

ABSTRACT In active tuberculosis (TB), Mycobacterium tuberculosis-specific T cells are compartmentalized more to the site of infection than to the circulating blood. Therefore, an M. tuberculosis-specific enzyme-linked immunospot (ELISPOT) assay with samples from the site of infection may permit a more sensitive or specific diagnosis of active central nervous system (CNS) TB than that achieved by the assay with blood alone. Therefore, we prospectively evaluated the usefulness of circulating and compartmentalized mononuclear cell (MC; i.e., peripheral blood mononuclear cell [PBMC] and cerebrospinal fluid [CSF] MC)-based ELISPOT assays (i.e., the T-SPOT.TB test) for the diagnosis of active TB in patients with suspected CNS TB. The clinical categories of CNS TB were classified as described previously (G. E. Thwaites, T. T. Chau, K. Stepniewska, N. H. Phu, L. V. Chuong, D. X. Sinh, N. J. White, C. M. Parry, and J. J. Farrar, Lancet 360:1287-1292, 2002). Thirty-seven patients with suspected CNS TB were enrolled over a 12-month period. Of these, 31 (84%) showed clinical manifestations of suspected TB meningitis and 6 (16%) gave indications of intracranial tuberculoma with disseminated TB. The final clinical categories of the 37 patients with suspected CNS TB were as follows: 12 (32%) were classified as having CNS TB (7 with confirmed TB, 3 with probable TB, and 2 with possible TB) and 25 (68%) were classified as not having active TB. The sensitivity and specificity of the PBMC ELISPOT assay were 91% (95% confidence interval [CI], 59% to 100%) and 63% (95% CI, 41% to 81%), respectively. By comparison, the sensitivity and specificity of the CSF MC ELISPOT assay were 75% (95% CI, 19% to 99%) and 75% (95% CI, 43% to 95%), respectively. When the ratio of the CSF MC ELISPOT assay results to the PBMC ELISPOT results was 2 or more, the sensitivity and specificity were 50% (95% CI, 7% to 93%) and 100% (95% CI, 74% to 100%), respectively. The ELISPOT assay with PBMCs and CSF MCs is a useful adjunct to the current tests for the diagnosis of CNS TB.