Appropriate non-carbapenems are not inferior to carbapenems as initial empirical therapy for bacteremia caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: a propensity score weighted multicenter cohort study.

The efficacy of empirical non-carbapenem antibiotics for extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia (ESBL-B) is still inconclusive. We conducted a multicenter retrospective cohort study to evaluate the efficacy of empirical non-carbapenem antibiotics for treating ESBL-B. Electronic medical records of individuals who were diagnosed with ESBL-B were reviewed between January 2010 and December 2014 at four university hospitals in Korea. Patients were classified into non-carbapenem and carbapenem groups according to the empirical antibiotic regimen. Patients treated with appropriate empirical antibiotics and who subsequently received carbapenems as definitive therapy were included in the analysis. The inverse probability of treatment weights, a statistical method that adjusts baseline statistics by giving weights based on propensity score, was used. During the study period, 232 adequately treated patients with ESBL-B were included in the analysis: 49 patients in the non-carbapenem group and 183 in the carbapenem group. The baseline characteristics and severity of infection were similar after propensity score weighting. The 30-day mortality rates for the two groups were not statistically significantly different (non-carbapenems 6.3% and carbapenems 11.4%; P = 0.42). In a multivariate analysis, empirical treatment with non-carbapenem antibiotics was not associated with 30-day all-cause mortality (HR 1.02, 95% CI 0.99-1.06, P = 0.14). In a subgroup analysis, empirical treatment with piperacillin-tazobactam was also not associated with 30-day all-cause mortality (HR 1.21, 95% CI 0.37-4.00, P = 0.75). Appropriate non-carbapenems were not inferior to carbapenems as initial empirical therapy for ESBL-B.

Clinical predictors of methicillin-resistance and their impact on mortality associated with Staphylococcus aureus bacteraemia.

We investigated the clinical predictors of methicillin-resistance and their impact on mortality in 371 patients with Staphylococcus aureus bacteraemia identified from two prospective multi-centre studies. Methicillin resistant S. aureus (MRSA) accounted for 42.2% of community-onset and 74.5% of hospital-onset cases. No significant clinical difference was found between patients infected with MRSA vs. methicillin-sensitive S. aureus (MSSA), except that the former were more likely to have had hospital-onset bacteraemia and received antibiotics in the preceding 90 days. After stratifying according to the acquisition site, prior antibiotic use was the only independent predictor of having MRSA in both community-onset and hospital-onset cases. The frequency of inappropriate empirical antibiotic therapy was higher in patients with MRSA than in those with MSSA bacteraemia. However, methicillin resistance was not a predictor of mortality in patients and the clinical characteristics and outcomes of both MRSA and MSSA bacteraemia were similar. This study indicates that there are no definitive clinical or epidemiological risk factors which could distinguish MRSA from MSSA cases with the exception of the previous use of antibiotics for having MRSA bacteraemia, which emphasises the prudent use of glycopeptide treatment of patients at risk for invasive MRSA infections.

Serious fungal infections in Korea.

Information on the incidence and prevalence of fungal infections is of critical value in public health policy. However, nationwide epidemiological data on fungal infections are scarce, due to a lack of surveillance and funding. The objective of this study was to estimate the disease burden of fungal infections in the Republic of Korea. An actuarial approach using a deterministic model was used for the estimation. Data on the number of populations at risk and the frequencies of fungal infections in those populations were obtained from national statistics reports and epidemiology papers. Approximately 1 million people were estimated to be affected by fungal infections every year. The burdens of candidemia (4.12 per 100,000), cryptococcal meningitis (0.09 per 100,000), and Pneumocystis pneumonia (0.51 per 100,000) in South Korea were estimated to be comparable to those in other countries. The prevalence of chronic pulmonary aspergillosis (22.4 per 100,000) was markedly high, probably due to the high burden of tuberculosis in Korea. The low burdens of allergic bronchopulmonary aspergillosis (56.9 per 100,000) and severe asthma with fungal sensitization (75.1 per 100,000) warrant further study. Oral candidiasis (539 per 100,000) was estimated to affect a much larger population than noted in previous studies. Our work provides valuable insight on the epidemiology of fungal infections; however, additional studies are needed.

Impact of appropriateness of empiric therapy on outcomes in community-onset bacteremia by extended-spectrum-ß-lactamase producing Escherichia coli and Klebisella pneumoniae definitively treated with carbapenems.

Despite a significant increase of bloodstream infection caused by extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae in the community-setting, information regarding clinical outcomes of inappropriate empiric therapy (IAT) in patients with those infections is limited. A multicenter-retrospective cohort study was conducted in four hospitals. A total of 249 adults were identified to have community-onset bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae, and definitively treated with carbapenems. According to the appropriateness of empiric therapy, individuals were divided into an appropriate empiric therapy (AT) group (n = 106) and IAT group (n = 143). Patients who received AT showed more severe underlying conditions including underlying solid cancer, healthcare-association and intensive care unit (ICU) care, compared to the IAT group. Primary bacteremia was more commonly found in the AT group than in the IAT group, while urinary tract infection predominated more frequently in the IAT group than in the AT group. Multivariate analysis using propensity score analysis indicated that inappropriateness of empiric therapy was not an independent risk factor for 30-day death. ICU care, respiratory tract infection and underlying liver, renal and connective tissue diseases were significantly associated with mortality. In patients with bloodstream infections caused by ESBL-producing E. coli and K. pneumoniae in the community-setting, delay in appropriate therapy was not associated with an increased rate of death if the patients were definitively treated with carbapenems.

Empirical combination of a ß-lactam to vancomycin may not improve outcomes of methicillin-susceptible Staphylococcus aureus bacteremia, compared to vancomycin monotherapy.

To evaluate effect of empirical combination of a ß-lactam to vancomycin and vancomycin monotherapy in Staphylococcus aureus bacteremia (MSSA-B), we conducted a retrospective cohort study. Electronic medical records of individuals who were diagnosed with MSSA-B between January 2005 and February 2015 at a tertiary care center were reviewed. Patients were classified into three groups according to empirical antibiotic regimen (BL group, ß-lactam; VAN group, vancomycin; BV group, combination of ß-lactam and vancomycin), and 30-day all-cause mortality of each group was compared. During the study period, 561 patients with MSSA-B were identified. After exclusion of 198 patients (36 with poly-microbial infection, 114 expired within 2 days, and 48 already received parenteral antibiotics) and a matching process, 46 patients for each group were included. Baseline characteristics were similar except for severity and comorbidity scores. The 30-day mortality for all three groups were not significantly different (BL 4.3%, VAN 6.5%, BV 8.7%; P = 0.909). In a multivariate analysis, type of empirical antibiotic regimen was not statistically associated with 30-day all-cause mortality. In comparison with the VAN group, the BV group yielded a HR of 0.579 (95% CI = 0.086-3.890, P = 0.574). Pitt bacteremia score was the only significant factor for mortality. The empirical combination of a ß-lactam to vancomycin was not associated with lower mortality in treating MSSA-B, compared to vancomycin monotherapy.

Suggested new breakpoints of anti-MERS-CoV antibody ELISA titers: performance analysis of serologic tests.

To provide optimal cut-off values of anti-Middle East respiratory syndrome coronavirus (MERS-CoV) serologic tests, we evaluated performance of ELISA IgG, ELISA IgA, IFA IgM, and IFA IgG using 138 serum samples of 49 MERS-CoV-infected patients and 219 serum samples of 219 rRT-PCR-negative MERS-CoV-exposed healthcare personnel and patients. The performance analysis was conducted for two different purposes: (1) prediction of neutralization activity in MERS-CoV-infected patients, and (2) epidemiologic surveillance of MERS-CoV infections among MERS-CoV-exposed individuals. To evaluate performance according to serum collection time, we used 'days post onset of illness (dpoi)' and 'days post exposure (dpex)' assessing neutralization activity and infection diagnosis, respectively. Performance of serologic tests improved with delayed sampling time, being maximized after a seroconversion period. In predicting neutralization activity, ELISA IgG tests showed optimal performance using sera collected after 21 dpoi at cut-off values of OD ratio 0.4 (sensitivity 100% and specificity 100%), and ELISA IgA showed optimal performance using sera collected after 14 dpoi at cut-off value of OD ratio 0.2 (sensitivity 85.2% and specificity 100%). In diagnosis of MERS-CoV infection, ELISA IgG exhibited optimal performance using sera collected after 28 dpex, at a cut-off value of OD ratio 0.2 (sensitivity 97.3% and specificity 92.9%). These new breakpoints are markedly lower than previously suggested values (ELISA IgG OD ratio 1.1, sensitivity 34.8% and specificity 100% in the present data set), and the performance data help serologic tests to be practically used in the field of MERS management.

Emergence of an extended-spectrum ß-lactamase-producing serotype K1 Klebsiella pneumoniae ST23 strain from Asian countries.

Extended-spectrum ß-lactamase (ESBL) production has been very rare in serotype K1 Klebsiella pneumoniae ST23 strains, which are well-known invasive community strains. Among 92 ESBL-producing strains identified in 218 isolates from nine Asian countries, serotype K1 K. pneumoniae strains were screened. Two ESBL-producing K. pneumoniae isolates from Singapore and Indonesia were determined to be serotype K1 and ST23. Their plasmids, which contain CTX-M-15 genes, are transferable rendering the effective transfer of ESBL resistance plasmids to other organisms.

Fatal scedosporiosis in multiple solid organ allografts transmitted from a nearly-drowned donor.

Scedosporium spp. is the most common mold infection in pneumonia resulting from near-drowning. Three fatal scedosporiosis cases developed after solid organ transplantation, probably transmitted from the nearly-drowned donor. One heart transplant recipient and two kidney transplant recipients developed fatal scedosporiosis following deceased donor transplantation from the same donor, a nearly-drowned victim of a suicide attempt. Genotypically, indistinguishable strains of Scedosporium auratiacum were recovered from the three recipients. Two liver transplant recipients from the same donor received prophylactic voriconazole without any subsequent signs of infection. To determine the safety of donation from nearly-drowned donors, a national traceback investigation was also performed of the causes of deaths in all transplant recipients who received organs from drowned donors between 2001 and 2013. Over 13 years, 2600 deceased donor transplants were performed in Korea. Among these 2600 deceased donor transplants, 27 (1%) victims of drowning donated their organs. From these 27 donors, 84 patients received organ transplants and 18 died, including the above three. We found no microbiologic evidence of invasive mold transmission from the nearly-drowned donors to the other 15 recipients. Although disseminated infection in the donor could not be demonstrated by culture, undiagnosed disseminated donor infection and transmission of Scedosporium spp. should be considered in near-drowning events.

Generic piperacillin/tazobactam is not associated with galactomannan false-positivity in adult patients with cancer: a case-control study.

Recent products of piperacillin/tazobactam (PTZ) from the original manufacturer, previously considered a major cause of galactomannan (GM) false-positivity, are reported not to be related to it. However, data regarding generic PTZ are limited and controversial. To evaluate the effect of generic PTZ on GM false-positivity in Korea, we performed a case-control study in adult patients with cancer. A case-control study was designed. Electronic medical records of cancer patients who were admitted and tested for serum GM between March and June 2014 at a tertiary care university hospital were reviewed. During the study period, a single generic PTZ (C manufacturer, Korea) was used. Patients who received PTZ within 24 h prior to serum GM testing were enrolled. Age- and GM test date-matched non-PTZ patients were selected as controls. A total of 110 patients received PTZ within 24 h prior to serum GM testing during the study period. The GM optical density index (ODI) of the PTZ group did not vary significantly from that of the control group (p = 0.251). The percentage of false-positive patients in the PTZ group was also similar to that of the control group (p = 0.538). There was no statistical relationship between GM ODI titer and time interval from PTZ administration (p = 0.095) or cumulative PTZ dose (p = 0.416). In a case-control study that evaluated 220 patients, a generic PTZ in Korea was not related to GM false-positivity.

Risk factors for levofloxacin-nonsusceptible Streptococcus pneumoniae in community-acquired pneumococcal pneumonia: a nested case-control study.

This study was performed to evaluate the clinical features of community-onset levofloxacin-nonsusceptible pneumococcal pneumonia and to identify risk factors for levofloxacin resistance. Using the database of a surveillance study of community-acquired pneumococcal infections in Asian countries, we conducted a nested case-control study to identify risk factors for levofloxacin-nonsusceptible S. pneumoniae in community-acquired pneumonia in adults. Of 981 patients with pneumococcal pneumonia, 46 (4.7 %) had levofloxacin-nonsusceptible S. pneumoniae, of whom 39 evaluable cases were included in the analysis. All cases were from Korea, Taiwan, and Hong Kong. Among patients with levofloxacin-susceptible S. pneumoniae, 490 controls were selected based on patient country. Of the 39 cases of levofloxacin-nonsusceptible pneumococcal pneumonia, 23 (59.0 %) were classified as healthcare-associated, while 164 (33.5 %) of the 490 controls of levofloxacin-susceptible S. pneumoniae (P = 0.001) were classified as healthcare-associated. Multivariate analysis showed that previous treatment with fluoroquinolones, cerebrovascular disease, and healthcare-associated infection were significantly associated with levofloxacin-nonsusceptible pneumococcal pneumonia (all P < 0.05). Levofloxacin-nonsusceptible pneumococci pose an important new public health threat in our region, and more information on the emergence and spread of these resistant strains will be necessary to prevent spread throughout the population.

Risk factors for cytomegalovirus gastrointestinal diseases in adult patients with cancer.

Cytomegalovirus (CMV) gastrointestinal (GI) disease has been noticed frequently in cancer patients, causing abdominal pain, diarrhea, and GI bleeding. However, little is known about its actual incidence, clinical presentation, and the risk factors for its development among cancer patients. To answer these questions, we analyzed all cases that occurred during an 18-year period at our center. A case-control study was performed to identify risk factors for CMV GI disease. Electronic medical records were reviewed from individuals who were admitted and diagnosed with CMV GI disease during the period of January 1995 through March 2013 at a tertiary care center. Two CMV disease-free cancer patients were matched as controls. A total of 98 episodes of CMV GI disease were included in this study, and the overall incidence rate was 52.5 per 100,000 cancer patients, with an increasing trend throughout the study period. According to multivariate analysis, male sex, low body mass index, lymphopenia, hematological malignancy, and steroid use and red blood cell transfusion within 1 month prior to the CMV disease were identified to be independent risk factors. Among these factors, RBC transfusion showed the highest odds ratio (OR = 5.09). Male sex, low body mass index, lymphopenia, hematological malignancy, steroid use, and red blood cell transfusion within 1 month prior to the CMV disease diagnosis were independent risk factors for the development of CMV GI disease in adult patients with cancer.

Serum albumin level as a predictor of intensive respiratory or vasopressor support in influenza A (H1N1) virus infection.

AIM: Low serum albumin levels occur in a variety of disease states and are related to in-hospital mortality and length of stay. The purpose of this study was to evaluate the association of commonly measured biochemical markers in critically ill patients such as serum albumin or C-reactive protein (CRP) with the need for intensive respiratory or vasopressor support (IRVS) in patients with 2009 influenza A (H1N1). METHODS: A total of 104 patients from an H1N1 registry database of 2436 patients were enrolled. Clinical characteristics and laboratory findings within 24 h of admission were reviewed to evaluate whether serum biochemical markers can be used as predictors of illness severity in adult patients with H1N1 based on the need for IRVS. RESULTS: Twenty-four (23.1%) of the 104 patients enrolled in the study received IRVS during the study period. Independent predictors of the need IRVS were serum glucose level on admission (OR 1.02; 95% CI 1.00-1.04; p = 0.021) and serum albumin level on admission (OR 0.12; 95% CI 0.02-0.63; p = 0.013). The diagnostic sensitivity of albumin levels for predicting the need for IRVS in patients with confirmed H1N1 with a cut-off value of 2.7 g/dl was 79.17% (95% CI 57.8-92.9), the specificity was 85.71% (95% CI 75.9-92.6), the positive predictive value was 63.3% (95% CI 43.9-80.1) and the negative predictive value was 93.0% (95% CI 84.3-97.7). The area under the receiver operation characteristic curve was 0.860 (95% CI 0.773-0.923) for albumin, 0.808 (95% CI 0.713-0.882) for glucose and 0.734 (95% CI 0.633-0.821) for CRP. CONCLUSIONS: Serum albumin levels and glucose levels on admission were predictors of the need IRVS in adult patients with H1N1. Based on these findings, the level of albumin at presentation may serve as a novel and simple early biomarker to identify patients at high risk for a complicated clinical course of disease.

Predictors of uropathogens other than Escherichia coli in patients with community-onset acute pyelonephritis.

AIM: A constant reduction in the incidence of community-onset acute pyelonephritis (CO-APN) caused by Escherichia coli has been shown with a parallel increase incidence caused by other organisms. Therefore, we evaluated the risk factors and outcome of non-E. coli as uropathogens in patients with community-onset APN. METHODS: As a part of a nationwide multicentre surveillance study conducted in Korea, a total of 416 patients with CO-APN were collected with their epidemiological, antibiotic treatment and outcome data. RESULTS: The risk factors and outcomes of non-E. coli as uropathogens were evaluated in a total of 416 patients with culture-confirmed CO-APN. Non-E. coli caused 127 cases (30.5%) of CO-APN. CO-APN caused by non-E. coli resulted in higher inappropriate empirical therapy (38.6% vs. 20.1%, p < 0.001), longer hospital stay (12.6 days vs. 6.7 days, p = 0.005) and higher 30-day mortality (9.4% vs. 3.8% p = 0.020) compared with CO-APN caused by E. coli. Multivariate analyses showed that male gender (OR, 3.48; CI, 2.13-5.67; p < 0.001), underlying haematological disease (OR, 5.32; CI, 1.17-24.254; p = 0.031), underlying benign prostate hyperplasia (OR, 2.61; CI, 1.02-6.74; p = 0.046), chronic indwelling urethral catheter (OR, 6.34; CI, 1.26-31.84; p = 0.025) and admission history in the previous 6 months (OR, 2.12; CI, 1.23-3.58; p = 0.005) were predictors for CO-APN caused by a non-E. coli isolate. CONCLUSIONS: Community-onset APN caused by non-E. coli represents a distinct subset of urinary tract infections with worse outcomes. The defined risk factors related with non-E. coli should be taken into consideration when empirical antibiotic therapy is prescribed in patients with community-onset APN.

Impact of a computerized alert system for bacteremia notification on the appropriate antibiotic treatment of Staphylococcus aureus bloodstream infections.

A computerized alert system (CAS) has been introduced to notify bacteremia in real time. We evaluated the impact of the CAS on the administration of appropriate antibiotics in patients with Staphylococcus aureus bloodstream infections (BSIs). We retrospectively reviewed the medical records of patients with S. aureus BSI for each 1-year control and intervention periods, before and after the implementation of the CAS. The proportions of appropriate antibiotic treatment were compared between the control and intervention periods. The 30-day mortality of S. aureus bacteremia was also assessed in the study population. A total of 313 patients were included in the study. Appropriate antibiotics were initiated 7 h earlier in the intervention period (mean time, 13.5 h vs. 20.0 h; p = 0.136). The administration of appropriate antibiotics within the 24 h after blood acquisition was similar between the two periods, but this significantly increased from 3.3% in the control period to 10.6% in the intervention during the 24-36 h interval (p = 0.012). In the subgroup analysis, similar trends were observed in patients with methicillin-resistant isolates (6.7% vs. 18.2%; p = 0.032) and hospital-onset infection (3.5% vs. 17.1 %; p = 0.004). The independent risk factors for 30-day mortality of S. aureus bacteremia were age, a high Pitt bacteremia score, an increased Charlson's weighted index of comorbidity, and hospital-onset infection, although the appropriateness of antibiotic therapy within 36 h and the CAS were not identified as predictors. The CAS increased the proportion of appropriate antimicrobial therapy during the 24-36 h interval after bacteremia onset in patients with S. aureus BSIs.

Association of levofloxacin resistance with mortality in adult patients with invasive pneumococcal diseases: a post hoc analysis of a prospective cohort.

OBJECTIVE: This study was conducted to identify risk factors for mortality and to evaluate the impact of antimicrobial resistance on outcome in adult patients with invasive pneumococcal disease (IPD). METHODS: A post hoc analysis of an observational cohort study on community-acquired pneumococcal infections was conducted and a total of 136 adult patients with IPD were analyzed in this study. RESULTS: Pneumonia was the most common type of infection (n = 84, 61.8 %), followed by primary bacteremia (n = 15, 11.0 %) and meningitis (n = 15, 11.0 %). One hundred and three patients (75.7 %) had concomitant pneumococcal bacteremia. The overall 30-day mortality rate was 26.5 % (36/136), and factors associated with 30-day mortality were corticosteroid use, presentation with septic shock, and development of acute respiratory distress syndrome (ARDS) (all P < 0.05). While penicillin and erythromycin resistance were associated with a lower mortality, an association between levofloxacin resistance and increased mortality was found in the univariate analysis; however, statistical significance was not reached (P = 0.083). Multivariable analysis showed that presentation with septic shock, corticosteroid use, development of ARDS, and levofloxacin resistance were independent factors associated with 30-day mortality. Of the five patients with IPD caused by levofloxacin-resistant Streptococcus pneumoniae, three (60 %) died within 30 days of diagnosis. CONCLUSION: Levofloxacin resistance was associated with increased mortality, along with septic shock, prior use of corticosteroids, and development of ARDS, in adult patients with IPD. Our data suggest that the emergence of levofloxacin resistance among invasive pneumococcal isolates is now becoming a challenge for clinicians managing community-acquired bacterial infections.

Fecal carriage of serotype K1 Klebsiella pneumoniae ST23 strains closely related to liver abscess isolates in Koreans living in Korea.

We determined the fecal carriage rate of serotype K1 Klebsiella pneumoniae in healthy Koreans and studied their genetic relationship with liver abscess isolates. We compared the carriage according to the country of residence. The stool specimens were collected through health promotion programs in Korea. K. pneumoniae strains were selected and tested for K1 by PCR. Serotype K1 isolates were characterized by multilocus sequence typing and pulsed field gel electrophoresis. A total of 248 K. pneumoniae isolates were obtained from 1,174 Koreans. Serotype K1 was identified in 57 (4.9%), of which 54 (94.7%) were ST 23 and were closely related to the liver abscess isolates. Participants aged >25 years showed a higher fecal carriage rate than those ≤ 25 (P = 0.007). The proportion of serotype K1 out of K. pneumoniae isolates in foreigners of Korean ethnicity who had lived in other countries was lower compared with those who had lived in Korea (5.6% vs 24.1%, P = 0.024). A substantial proportion of Koreans >25 years carries serotype K1 K. pneumoniae ST23 strains, which are closely related to liver abscess isolates. Differences in carriage rates by country of residence suggests that environmental factors might play an important role in the carriage of this strain.

Tacrolimus as a risk factor for tuberculosis and outcome of treatment with rifampicin in solid organ transplant recipients.

BACKGROUND: The purpose of this study was to investigate the incidence, risk factors, and treatment outcome of tuberculosis (TB) in solid organ transplant (SOT) recipients treated with rifampicin. METHODS: The incidence density of TB was calculated by a retrospective cohort study. Risk factors for TB were analyzed by a nested case-control study. Treatment outcome and effects of anti-TB drugs on immunosuppressants and allograft were compared between patients whose initial 2-month intensive regimen included rifampicin and those whose intensive regimen did not. RESULTS: Among the 2144 SOT recipients over 16 years, 40 cases of TB were found (1.7%). The incidence density was 372 cases per 10(5) patient years (95% confidence interval [CI], 270-503), which was 4 times higher than for the general Korean population (90 cases per 10(5) person years). The median time to the development of TB was 234 days (range, 33-3940 days). The use of tacrolimus (odds ratio [OR] 4.90; 95% CI, 1.74-13.80; P = 0.003) and cytomegalovirus (CMV) infection within the prior 3 months (OR 4.62; 95% CI, 1.44-14.87; P = 0.01) were found to be risk factors for TB. Patients whose intensive regimen included rifampicin were more likely to have an increased dose of calcineurin inhibitors than patients whose intensive regimen did not include rifampicin (13/15 [86.7%] vs. 3/14 [21.4%], P = 0.001). Graft rejection and mortality did not differ between the 2 groups. CONCLUSIONS: Use of tacrolimus and CMV infection were major risk factors for TB in SOT recipients. The graft outcome and mortality did not differ whether rifampicin was used or not during the first 2-month intensive phase.

Impact of inappropriate empiric antimicrobial therapy on outcome in Pseudomonas aeruginosa bacteraemia: a stratified analysis according to sites of infection.

BACKGROUND: The purpose of this study was to evaluate the impact of inappropriate empiric antimicrobial therapy on the outcome of Pseudomonas aeruginosa bacteraemia according to the primary infection site. METHODS: A retrospective cohort study including 202 patients with P. aeruginosa bacteraemia was performed. High-risk sites of infection were defined as the lung, intra-abdominal non-hepatobiliary tract or unknown source. RESULTS: Of the 202 patients with P. aeruginosa bacteraemia, 80 (39.6%) had received inappropriate empiric antimicrobial therapy. No significant difference in the 30-day mortality rate was found between the inappropriate therapy group and the appropriate therapy group (19/80 [23.8%] vs. 32/122 [26.2%], P = 0.692). Patients with pneumonia or non-hepatobiliary tract intra-abdominal infection showed significant association with high mortality, while those with urinary tract or hepatobiliary tract infection showed negative associations with mortality. In the subgroup analysis including 98 patients with high-risk sites of infection, the mortality rate of the inappropriate therapy group was significantly higher than that of the appropriate therapy group (14/26 [53.8%] vs. 23/72 [31.9%], P = 0.035). Inappropriate empiric antimicrobial therapy was also found to be one of the independent risk factors for mortality in patients with high-risk sites of infection (odds ratio [OR] 8.69; 95% confidence interval [CI] 1.86-40.59), along with renal disease, corticosteroid use, polymicrobial infection and higher Pitt bacteraemia score. CONCLUSION: Inappropriate empiric antimicrobial therapy adversely affected the outcome of P. aeruginosa bacteraemia in patients with high-risk sites of infection. Our data suggest that the impact of inappropriate antimicrobial therapy on the outcome of P. aeruginosa bacteraemia may be dependent on the primary site of infection.

Changing etiology of community-acquired bacterial meningitis in adults: a nationwide multicenter study in Korea.

Epidemiologic data on the etiologic organisms is important for appropriate empirical antibiotic treatment of bacterial meningitis. We identified the etiologies of community-acquired bacterial meningitis in Korean adults and the associated epidemiological factors. A retrospective, multicenter nationwide study was carried out. Patients 18 years of age or older with community-acquired bacterial meningitis with a confirmed pathogen were enrolled. Demographic, clinical, and microbiological data were collected. One hundred and ninety-five cases were collected. Streptococcus pneumoniae was the most common pathogen (50.8%), followed by Staphylococcus aureus (10.3%), Klebsiella pneumoniae (7.7%), Listeria monocytogenes (6.7%), and group B Streptococcus (3.1%). The penicillin resistance rate of the S. pneumoniae was 60.3%; 40.0% of the organisms were not susceptible to third-generation cephalosporins. The combination of third-generation cephalosporin with vancomycin was used in 76.3% of cases. Steroids were given before or with the first dose of antibiotics in 37.4% of patients. The 30-day mortality rate was 20.5% and neurological sequelae developed in 15.6% of cases. S. pneumoniae was the most common organism identified in community-acquired bacterial meningitis among Korean adults. S. aureus, K. pneumoniae, L. monocytogenes, and group B Streptococcus were also common. S. pneumoniae had high rates of resistance to penicillin and third-generation cephalosporins.

Early cidofovir administration might be associated with a lower probability of respiratory failure in treating human adenovirus pneumonia: a retrospective cohort study.

OBJECTIVE: To compare outcomes of early and delayed treatment with cidofovir for human adenovirus (HAdV) pneumonia. METHODS: A retrospective cohort study in Korean military hospitals was conducted between January 2012 and December 2018. Patients with potentially severe HAdV pneumonia with risk factors for respiratory failure were included and divided into early (within 7 days from symptom onset) and delayed (after 7 days from symptom onset) treatment groups. The primary outcome was respiratory failure development within 21 days after symptom onset. RESULTS: A total of 89 patients with potentially severe HAdV pneumonia were enrolled in the cohort; they included 62 early and 27 delayed treatment patients. All patients were males in their early 20s. Significantly fewer patients in the early treatment group progressed to respiratory failure (8/62, 12.9%), compared to the delayed group (18/27, 66.7%, p < 0.001). Early treatment was associated with a lower 21-day probability of respiratory failure by the Kaplan-Meier method (p < 0.001). On multivariate analysis, monocyte count, hypoxaemia, confusion, whole lung involvement, and early cidofovir treatment within 7 days from symptom onset were included, and monocyte count (HR 0.995, 95%CI 0.991-1.000, p 0.042), confusion (HR 4.964, 95%CI 1.189-20.721, p = 0.028), and early cidofovir treatment (HR 0.319, 95%CI 0.115-0.883, p = 0.028) were significantly associated with respiratory failure. CONCLUSIONS: Early administration of cidofovir was associated with a lower hazard for respiratory failure development. It is suggested that cidofovir be administered within 7 days from symptom onset to prevent respiratory failure in patients with potentially severe HAdV pneumonia.