Generative adversarial network for automatic quantification of Coronavirus disease 2019 pneumonia on chest radiographs.

PURPOSE: To develop a generative adversarial network (GAN) to quantify COVID-19 pneumonia on chest radiographs automatically. MATERIALS AND METHODS: This retrospective study included 50,000 consecutive non-COVID-19 chest CT scans in 2015-2017 for training. Anteroposterior virtual chest, lung, and pneumonia radiographs were generated from whole, segmented lung, and pneumonia pixels from each CT scan. Two GANs were sequentially trained to generate lung images from radiographs and to generate pneumonia images from lung images. GAN-driven pneumonia extent (pneumonia area/lung area) was expressed from 0% to 100%. We examined the correlation of GAN-driven pneumonia extent with semi-quantitative Brixia X-ray severity score (one dataset, n = 4707) and quantitative CT-driven pneumonia extent (four datasets, n = 54-375), along with analyzing a measurement difference between the GAN and CT extents. Three datasets (n = 243-1481), where unfavorable outcomes (respiratory failure, intensive care unit admission, and death) occurred in 10%, 38%, and 78%, respectively, were used to examine the predictive power of GAN-driven pneumonia extent. RESULTS: GAN-driven radiographic pneumonia was correlated with the severity score (0.611) and CT-driven extent (0.640). 95% limits of agreements between GAN and CT-driven extents were -27.1% to 17.4%. GAN-driven pneumonia extent provided odds ratios of 1.05-1.18 per percent for unfavorable outcomes in the three datasets, with areas under the receiver operating characteristic curve (AUCs) of 0.614-0.842. When combined with demographic information only and with both demographic and laboratory information, the prediction models yielded AUCs of 0.643-0.841 and 0.688-0.877, respectively. CONCLUSION: The generative adversarial network automatically quantified COVID-19 pneumonia on chest radiographs and identified patients with unfavorable outcomes.

Comparison of Antibody Response Elicited by ChAdOx1 and BNT162b2 COVID-19 Vaccine.

BACKGROUND: ChAdOx1 and BNT162b2 vaccines are currently commonly used against coronavirus disease 2019 worldwide. Our study was designed to determine the serostatus and relative levels of anti-S and neutralizing antibodies in patients who were administered either ChAdOx1 or BNT162b2 vaccine. In addition, we investigated whether the antibody response to each vaccine differed according to sex and age. METHODS: Healthcare workers (HCWs) at a general hospital who were vaccinated with two doses of either ChAdOx1 or BNT162b2 were invited to participate in this prospective cohort study. Blood samples of HCWs vaccinated with both ChAdOx1 doses over a period of 12 weeks were collected at weeks 4 and 8 post first vaccination and 2 weeks post second vaccination. Blood samples of HCWs vaccinated with BNT162b2 were collected in the third week after the first dose, and the second dose was then administered on the same day; two weeks post second dose (5 weeks after the first dose), blood samples were collected to assess the antibody response. The titers of anti-S antibodies against the severe acute respiratory syndrome coronavirus 2 spike (S) protein receptor-binding domain and the neutralizing antibodies in the collected blood were evaluated. RESULTS: Of the 309 HCWs enrolled in the study, 205 received ChAdOx1 and 104 received BNT162b2. Blood samples from participants receiving either the ChAdOx1 or BNT162b2 vaccine exhibited substantial anti-S and neutralizing antibody seropositivity subsequent to the second dose. All participants (100%) from both vaccine groups were seropositive for anti-S antibody, while 98% (201/205) of ChAdOx1-vaccinated individuals and 100% (104/104) of BNT162b2-vaccinated individuals were seropositive for neutralizing antibodies. The median levels of anti-S and neutralizing antibodies were significantly higher in the BNT162b2-vaccinated group than the ChAdOx1-vaccinated group; in particular, anti-S antibody titers of 1,020 (interquartile range, 571.0-1,631.0) U/mL vs. 2,360 (1,243-2,500) U/mL, P < 0.05, were recorded for the ChAdOx1 and BNT162b2 groups, respectively, and neutralizing antibody titers of 85.0 (65.9-92.1%) vs. 95.8 (94.4-96.6%), P < 0.05, were recorded for the ChAdOx1 and BNT162b2 groups, respectively. In the ChAdOx1 vaccine group, the neutralizing antibody level was significantly higher in women than in men (85.7 [70.3-92.5%] vs. 77.7 [59.2-91.0%], P < 0.05); however, the neutralizing antibody titer in the BNT162b2 vaccine group did not vary between the two sexes (95.9 [95.2-96.6%] vs. 95.2 [93.5-96.3%], P = 0.200). Analysis of the correlation of antibody profiles with age revealed that the levels of anti-S antibodies and signal inhibition rate (SIR) of neutralizing antibodies decreased significantly with age. CONCLUSION: Both the ChAdOx1- and BNT162b2-vaccinated groups showed high seropositivity for anti-S and neutralizing antibodies. The SIR of neutralizing antibodies in the ChAdOx1 vaccine group was higher in women than in men. Enhanced antibody responses were observed in participants vaccinated with BNT162b2 compared to those vaccinated with the ChAdOx1 vaccine.

Reactogenicity after the first and second doses of BNT162b2 mRNA coronavirus disease vaccine: a single-center study.

PURPOSE: This study was conducted to determine differences in adverse events associated with the first and second doses of the BNT162b2 coronavirus disease 2019 vaccine based on the age and sex of recipients. MATERIALS AND METHODS: An online survey on the post-vaccination adverse events of healthcare workers was conducted from March 2021 to April 2021. The differences in the types of adverse events, including severity, onset time, and duration of symptoms, and how the adverse events were dealt with by the patient were analyzed based on the age and sex. The profiles of adverse events were compared after the first and second vaccination doses. RESULTS: Among the 131 participants who participated in the online survey out of 208 vaccine recipients, 43 and 80 recipients of the BNT162b2 vaccine experienced adverse events after the first and second dose, respectively. No sex-related differences were observed in the profiles of adverse events in vaccinated recipients. The overall frequency of adverse events did not differ based on age after the first dose. After the second dose, the frequency of adverse events, including both local and systemic reactions was significantly higher in the younger age group than in the older age group. CONCLUSION: The BNT162b2 vaccine resulted in a higher frequency of adverse events after the second dose than after the first dose especially in the younger age group; however, no sex-related differences associated with these adverse events were observed.

Rapidly Declining SARS-CoV-2 Antibody Titers within 4 Months after BNT162b2 Vaccination.

The efficacy and safety of the BNT162b2 vaccine are known, but antibodies are expected to decrease over time after vaccination. We collected blood samples from 104 fully vaccinated health care workers at 3 and 5 weeks after first vaccination and 4 months after second vaccination. Antibody titers and neutralizing antibodies were measured. In our study, both antibody titers and neutralizing antibodies increased significantly at 5 weeks after first vaccination but decreased rapidly at 4 months after second vaccination. Additionally, the results showed a significant decrease regardless of gender or age. Further studies are needed to help determine the interval of SARS-CoV-2 vaccinations.

SARS-CoV-2 Antibody Response to the BNT162b2 mRNA Vaccine in Persons with Past Natural Infection.

There are still no agreed guidelines on the vaccination of coronavirus disease 2019 (COVID-19) for previously infected patients. Here, we present two seropositive healthcare workers (HCWs) working in an isolation ward who recovered from COVID-19 in April 2020 and got vaccinated with BNT162b2 vaccine in March 2021. We have assessed the clinical course, vaccine-related adverse events, and antibody response after natural infection and after first and second dose vaccination. One of the two HCWs was asymptomatic during quarantine, but the other had mild upper respiratory infection symptoms 1 day before admission, and the symptoms continued for 9 days. There was no pneumonic infiltration in chest X-ray in both patients, and no COVID-19 specific treatment was administered. Total immunoglobulin antibody and neutralizing antibody to anti-spike protein receptor-binding domain of severe acute respiratory syndrome coronavirus 2 were confirmed to be present in both HCWs in blood tests performed at 2 weeks and 4 weeks after discharge. Antibody response to mRNA vaccination showed marked elevation after the first vaccination, which was 30-40 times higher than that of antibody titer after natural infection in each patient (83.2 U/mL vs. > 2,500 U/mL in patient 1; 61.6 U/mL vs. > 2,500 U/mL in patient 2). Signal inhibition rate of neutralizing antibodies was also increased to over 97%. Due to this increased effect, there was little difference in antibody levels after the first and second dose. Both patients 1 and 2 suffered more from adverse vaccine reactions after the second vaccination than from COVID-19 symptoms.

Estimating the Force of Infection with Helicobacter pylori in Japan.

BACKGROUND: Although the seroprevalence against Helicobacter pylori (H. pylori) in Japan has declined over the birth year, Japanese people have yet exhibited a relatively high risk of gastric cancer. The present study employed mathematical models to estimate the time- and age-dependent force of infection with H. pylori in Japan, predicting the future seroprevalence by time and age. METHODS: We investigated the published seroprevalence data against H. pylori in Japan from 1980-2018. Solving the McKendrick partial differential equation model, the seroprevalence was modeled as a function of survey year and age. Maximum likelihood estimation was conducted to estimate parameters governing the time- and age-dependent force of infection. RESULTS: Among all fitted models, the time-dependent and age-independent model with an exponentially decaying force of infection over years was most favored. Fitted models indicated that the force of infection started to decrease during and/or shortly after the World War II. Using the parameterized model, the predicted fraction seropositive at the age of 40 years in 2018 was 0.22, but it is expected to decrease to 0.13 in 2030 and 0.05 in 2050, respectively. CONCLUSION: The time dependence was consistent with the decline in the force of infection as a function of the birth year. The force of infection has continuously and greatly declined over time, implying the diminished transmission of H. pylori through the time course and small chance of persistence. These findings are critical to anticipate the future decline in gastric cancer incidence.

Emphysematous Pyelonephritis Caused by Citrobacter freundii in a Patient with Type 2 Diabetes and Neurogenic Bladder.

Emphysematous pyelonephritis (EPN) is a rare, life-threatening complication of upper urinary tract infections that is characterized by the presence of gas in the renal parenchyma and perirenal space. It commonly occurs in diabetic patients. Escherichia coli are the most common causative organisms, with few reports implicating Citrobacter freundii as the etiologic agent in EPN. A 57-year-old woman with diabetes and neurogenic bladder visited at our department with confused mentality, myalgia, and general weakness. Further investigation revealed that the patient suffered from unilateral EPN with sepsis caused by C. freundii. The patient's condition was improved considerably with percutaneous drainage and use of intravenous antibiotics for several weeks. However, renal function eventually deteriorated to permanent renal failure, which required hemodialysis. In conclusion, C. freundii may be the causative pathogen of EPN in a patient with type 2 diabetes and neurogenic bladder.

Toll-like receptor 2 and Muc2 expression on human intestinal epithelial cells by Gymnophalloides seoi adult antigen.

Goblet cell hyperplasia and mucin hypersecretion are important for the expulsion of the intestinal trematode, Gymnophalloides seoi , from mice. However, regulatory mechanisms underlying these processes remain elusive. To better understand the effects of G. seoi antigen on the host's intestinal epithelial cells, we determined whether G. seoi induces expression of Toll-like receptors (TLRs) and mucin-related (MUC) genes on a human intestinal epithelial cell line (HT29 cells). We treated HT29 cells with G. seoi or other adult helminth antigens and measured mRNAs of TLRs and MUCs. We also performed reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry to determine whether TLR and MUC expression is regulated by interferon (IFN)-gamma, interleukin-4, or monoclonal antibodies (mAbs) against G. seoi 46 kDa antigen. Gymnophalloides seoi antigen significantly induced expression of TLR2 and MUC2 in HT29 cells, and IFN-gamma was found to upregulate TLR2 expression on the surface of the cells. The expression of MUC2 was increased by IFN-gamma, but was decreased significantly via the combination of mAbs-to-human TLRs and G. seoi antigen. These results demonstrated that G. seoi antigen upregulates TLR2 and MUC2 expression on human intestinal epithelial cells. These effects reflect a helminth-induced, IFN-gamma-dependent, and innate mucosal immune mechanism in this human intestinal cell line.

Clinical responses to smallpox vaccine in vaccinia-naive and previously vaccinated populations: undiluted and diluted Lancy-Vaxina vaccine in a single-blind, randomized, prospective trial.

We conducted a single-blind, randomized trial of 2 dilutions (1:1 or 1:10) of Lancy-Vaxina vaccine (Berna Biotech) in vaccinia-naive persons (n=36) and persons previously vaccinated >25 years ago (n=76). All vaccinees responded successfully to the vaccination. There were no significant differences in the size of the skin lesions, the number of adverse events, the amount of viral shedding, or the level of antibody responses between the undiluted (n=56) and diluted (n = 56) vaccine groups. Compared with vaccinia-naive persons, previously vaccinated persons exhibited significantly smaller and more rapidly evolving skin lesions and fewer adverse events. Previously vaccinated persons had significantly higher neutralizing antibody levels before the administration of the study vaccine than vaccinia-naive persons, and viral shedding from lesions in previously vaccinated persons was lower and diminished more rapidly than from lesions in vaccinia-naive persons.

Production of C-reactive protein in Escherichia coli-infected patients with liver dysfunction due to liver cirrhosis.

To assess the effect of liver dysfunction on the production of C-reactive protein (CRP), CRP levels were evaluated in patients with Escherichia coli bacteremia with or without liver cirrhosis (LC). Thirty patients of each kind were selected as case and control groups, respectively. A matched control of 30 LC patients without acute infection was also included. In the patients with E. coli bacteremia, median CRP was 6.2 mg/dL (range 0.2-22.1) in the LC patients and 14.6 mg/dL (range 5.8-39.6) in the patients without liver dysfunction (P < 0.001). In the advanced LC patients in Child-Pugh class C, median CRP was 5.0 mg/dL (range 0.2-12.1) in patients with E. coli bacteremia and 0.5 mg/dL (range 0.1-1.2) in patients without acute infection (P < 0.001). Our data suggest that, although CRP levels are reduced in response to acute infection, production is nevertheless maintained even in patients with advanced liver dysfunction.

Risk factors for antimicrobial resistance and influence of resistance on mortality in patients with bloodstream infection caused by Pseudomonas aeruginosa.

This study was conducted to evaluate risk factors for antimicrobial resistance and influence of resistance on mortality in Pseudomonas aeruginosa bacteremia. Data on 190 patients with P. aeruginosa bacteremia were analyzed retrospectively. Antimicrobial resistance to antipseudomonal antibiotics was evaluated. The main outcome measure was 30-day mortality. In P. aeruginosa bacteremia, resistance rates to piperacillin (PIP), ceftazidime (CAZ), ciprofloxacin (CIP), and imipenem (IPM) were 29 (56/190), 19 (36/190), 17 (32/190) and 15% (28/190), respectively. Prior uses of fluoroquinolones or carbapenems were independent risk factors for resistance to CIP and IPM, and prior use of extended-spectrum cephalosporins was a risk factor for PIP-R. An indwelling urinary catheter was a risk factor for PIP-R, CAZ-R, and CIP-R. An invasive procedure was a risk factor for CIP-R and IPM-R. The 30-day mortality rate was 44% (33/75) in patients infected by strains resistant to any of the antipseudomonal antibiotics, but 33.9% (39/115) in those by strains susceptible to all antipseudomonal antibiotics (p = 0.161). Among patients with bloodstream infection due to antimicrobial-resistant P. aeruginosa, those infected by IPM-R strains had the highest mortality (IPM-R, 53.6% vs. CAZ-R, 47.2% vs. CIP-R 46.9%, PIP-R, 39.3%). In this study regarding P. aeruginosa bacteremia, prior uses of fluoroquinolones, carbapenems, or extended-spectrum cephalosporins, a prior invasive procedure, and an indwelling urinary catheter were found to be associated with antimicrobial resistance. The patients with bloodstream infection caused by antimicrobial-resistant P. aeruginosa, especially to imipenem, had a tendency toward higher mortality than those infected by susceptible strains.

Clinical epidemiology of ciprofloxacin resistance and its relationship to broad-spectrum cephalosporin resistance in bloodstream infections caused by Enterobacter species.

OBJECTIVES: To evaluate the clinical features of ciprofloxacin-resistant Enterobacter bacteremia and to examine the risk factors for ciprofloxacin resistance in Enterobacter species isolates causing bacteremia. DESIGN: A case-control study. SETTING: A 1,500-bed, tertiary-care university hospital and referral center. PATIENTS: All patients older than 16 years with Enterobacter species isolated from blood were enrolled. The medical records of 183 patients with clinically significant Enterobacter bacteremia from January 1998 to December 2002 were identified. We compared patients with bacteremia caused by ciprofloxacin-susceptible isolates with patients with bacteremia caused by ciprofloxacin-resistant isolates. RESULTS: Twenty-three (12.6%) of the patients had bacteremia caused by isolates resistant to ciprofloxacin. There were no significant differences in age, gender, underlying diseases, primary site of infection, or Acute Physiology and Chronic Health Evaluation II score between the ciprofloxacin-resistant and the ciprofloxacin-susceptible groups. Broad-spectrum cephalosporin resistance, defined as resistance to cefotaxime or ceftazidime in vitro, was detected in 21 (91.3%) of 23 ciprofloxacin-resistant isolates compared with 65 (40.6%) of 160 ciprofloxacin-susceptible isolates (P < .001). Multivariate analysis revealed that independent risk factors for ciprofloxacin resistance were the prior receipt of fluoroquinolones (P < .001) and broad-spectrum cephalosporin resistance (P < .001). CONCLUSIONS: In Enterobacter species isolates causing bacteremia, ciprofloxacin resistance was closely associated with the prior receipt of fluoroquinolones and broad-spectrum cephalosporin resistance. The close relationship between ciprofloxacin resistance and broad-spectrum cephalosporin resistance is particularly troublesome because it severely restricts the therapeutic options for Enterobacter species infection.

Bloodstream infections caused by antibiotic-resistant gram-negative bacilli: risk factors for mortality and impact of inappropriate initial antimicrobial therapy on outcome.

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.

Risk factors for and clinical outcomes of bloodstream infections caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae.

OBJECTIVE: To evaluate risk factors and treatment outcomes of bloodstream infections caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP). DESIGN: Retrospective case-control study. Stored blood isolates of K. pneumoniae were tested for ESBL production by NCCLS guidelines, double-disk synergy test, or both. SETTING: A 1,500-bed, tertiary-care university hospital and referral center. PATIENTS: Sixty case-patients with bacteremia due to ESB-KP were compared with 60 matched control-patients with non-ESBL-KP. RESULTS: There were no significant differences in age, gender, APACHE II score, or underlying diseases between the groups. Independent risk factors for infections caused by ESBL-KP were urinary catheterization, invasive procedure within the previous 72 hours, and an increasing number of antibiotics administered within the previous 30 days. Complete response rate, evaluated 72 hours after initial antimicrobial therapy, was higher among control-patients (13.3% vs 36.7%; P = .003). Treatment failure rate was higher among case-patients (35.0% vs 15%; P = .011). Overall 30-day mortality rate was 30% for case-patients and 28.3% for control-patients (P = .841). Case-patients who received imipenem or ciprofloxacin as a definitive antibiotic had 10.5% mortality. The mortality rate for initially ineffective therapy was no higher than that for initially effective therapy (9.1% vs 11.1%; P = 1.000), but statistical power was low for evaluating mortality in the absence of septic shock. CONCLUSION: For K. pneumoniae bacteremia, patients with ESBL-KP had a higher initial treatment failure rate but did not have higher mortality if antimicrobial therapy was appropriately adjusted in this study with limited statistical power.

Bloodstream infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for mortality and treatment outcome, with special emphasis on antimicrobial therapy.

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.

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

BACKGROUND: Enterobacter 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. METHODS: A 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. RESULTS: Of 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). CONCLUSIONS: Broad-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.

Clinical outcome of bacteremic spontaneous bacterial peritonitis due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

BACKGROUND: This study was conducted to evaluate the risk factors for infection and clinical outcomes of bacteremic spontaneous bacterial peritonitis (SBP) due to ESBL-producing E. coli and K. pneumoniae, in patients with advanced liver cirrhosis. METHODS: The ESBL production was determined by NCCLS guidelines and/or double-disk synergy tests, on stored E. coil and K. pneumoniae blood isolates collected between 1998 and 2002. Of the patients with advanced liver cirrhosis, 15 case patients, with SBP due to ESBL-producers, were compared with 30 matched controls, with SBP due to non-ESBL-producers. RESULTS: There were no significant differences in age, sex, Child-Pugh scores, or APACHE II scores between the two groups. Significant factors associated with infection by ESBL-producing organisms, according to univariate analysis, were: ICU care, indwelling urinary catheter, central venous catheterization, an invasive procedure within the previous 72 hours, and prior use of antibiotics within the previous 30 days. When assessing the clinical response at 72 hours after the initial antimicrobial therapy, the treatment failure rate was significantly higher in the ESBL group (73.3% vs. 16.7%, p<0.001). Also, overall 30-day mortality rates were 60% (9/15) in the ESBL groups and 23.3% (7/30) in the control group (p=0.015). CONCLUSION: Among patients with advanced liver cirrhosis, bacteremic SBP due to ESBL-producing E. coil and K. pneumoniae was associated with adverse outcomes, and significantly higher mortality.

Epidemiology and clinical features of bloodstream infections caused by AmpC-type-beta-lactamase-producing Klebsiella pneumoniae.

Cases of bacteremia caused by AmpC-type-beta-lactamase-producing Klebsiella pneumoniae isolates were retrospectively studied to determine the epidemiologic features and clinical outcomes of bloodstream infections. Among 389 blood isolates recovered from 1998 to 2002, 65 isolates (16.7%) were found to be extended-spectrum beta-lactamase (ESBL) or AmpC beta-lactamase producers. The beta-lactamases from 61 of the 65 isolates were characterized; 28 of 61 isolates produced AmpC-type enzymes (14 isolates each produced DHA-1 and CMY-1-like enzymes), 32 isolates produced TEM or SHV-related ESBLs, and 1 isolate produced a CTX-M-14-like enzyme. To compare the clinical features and outcomes of bloodstream infections caused by AmpC producers with those caused by TEM- or SHV-related ESBL producers, 27 patients infected with isolates producing AmpC-type enzymes (AmpC group) and 25 patients infected with isolates producing TEM- or SHV-related enzymes (ESBL group) were analyzed. There was no significant difference between the AmpC and the ESBL groups in terms of risk factors. When the initial response was assessed at 72 h after antimicrobial therapy, the treatment failure rate for the AmpC group was 51.9% (14 of 27 patients) and the 7- and 30-day mortality rates were 14.8 and 29.6%, respectively, which were similar to those for the ESBL group. When the mortality rate for the patients who received extended-spectrum cephalosporins as definitive treatment was assessed, all four patients in the DHA-1 group and one of three patients in the CMY-1-like group died. In summary, the prevalence of AmpC enzyme-producing K. pneumoniae was high at the Seoul National University Hospital, and the clinical features and outcomes for the patients infected with AmpC-producing organisms were similar to those for the patients infected with TEM- or SHV-related ESBL producers.