Frequent Causative Pathogen Research Articles

Streptococcus pneumoniae serotype distribution in Bangladeshi under-fives with community-acquired pneumonia pre-10-valent pneumococcal conjugate vaccination

BackgroundStreptococcus pneumoniae is the most frequent causative pathogen of bacterial pneumonia in children worldwide. Bangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in their national immunization program for infants in 2015. We assessed its potential coverage in under-fives with community-acquired pneumonia (CAP) in the years before PCV10 was introduced.MethodsA total of 1502 childhood pneumonia cases (< 5 year olds living in the urban section Kamalapur, Dhaka) were enrolled between 2011 and 2013. Acute phase and late (convalescent) serum samples were collected from 1380 cases. Serotype-specific pneumococcal antibody concentrations were measured using a 25-plex immunoassay panel. Pneumococcal CAP was diagnosed based on a serotype-specific pneumococcal antibody response.ResultsS. pneumoniae was serologically identified as causative pathogen in 406/1380 (29%) cases. The five most prevalent serotypes were (in descending order) 11A, 22F, 3, 2 and 19F. Based on the percentage of pneumonia cases associated with PCV10 vaccine types, the potential PCV10 coverage was 29% (116/406).ConclusionsIn almost a third of the studied cases S. pneumoniae was identified as a causative pathogen. Because of the characteristics of the immunoassay, this might well be a gross underestimation. Nevertheless, the potential PCV10-coverage was low. Given the high serotype diversity, the region might benefit greatly from a higher-coverage PCV or recombinant protein vaccine.

Trends in surveillance indicators for central catheter-associated bloodstream infections in a tertiary hospital in Switzerland

Central line-associated bloodstream infections (CLABSI) are associated with relevant morbidity and mortality. Longitudinal dynamics in CLABSI incidence and the spectrum of causative microorganisms are limited. We aimed to describe trends in CLABSI incidence, use of central lines, and causative pathogens. We analysed prospectively collected data on CLABSI at a Swiss tertiary care hospital between January 2016 and December 2023. We investigated longitudinal changes of incidence densities, catheter utilization and causative pathogens. A total of 707 CLABSI were observed, corresponding to an incidence density of 1.69 (95% CI 1.56 - 1.81) CLABSI per 1000 catheter-days. There was no significant trend of CLABSI incidence density per 1000 catheter-days (z=0.86, P=0.391), but an increase of catheter utilization ratio (z=8.88, P<0.001). Coagulase-negative staphylococci (CNS) (n=207, 23.4%) and Enterococcus spp. (n=134, 15.2%; E. faecium n=94, 10.6%; E. faecalis n=37, 4.1%; other Enterococcus spp. n=3, 0.34%) were the most frequent causative pathogens. Over the years, the proportion of Enterococcus spp. (z=3.4, P<0.001), driven by an increase of E. faecium (z=3.2, P=0.001), and yeast (z=2.3, P=0.020) increased, whereas CNS decreased (z=-6.1, P<0.001). Prospective CLABSI surveillance indicated stable incidence densities per 1000 catheter-days, but there were significant shifts of causative microorganisms over time.

P483 IMPACT OF AN ENDOCARDITIS TEAM ON PROGNOSIS: PRELIMINARY RESULTS

Abstract Infective endocarditis (IE) is a life–threatening microbial infection with high mortality rate (6–50% in–hospital and 19–82% at 5–years)1.Guidelines for management of infective endocarditis underline the importance of multidisciplinary approach with an Endocarditis Team (ET) for the complexity of disease and for prognosis which depends on patients’ characteristics, microorganisms involved and local or systemic complications.ET includes specialists that define multimodality imaging approach to confirm diagnosis and to exclude local or systemic complications, discuss timing of antibiotic therapy, indication and timing of surgical treatments and follow–up. This study was a retrospective analysis based on a population of 86 patients from Infermi Hospital, Rimini, who received a diagnosis of IE from 2019 to 2021 thanks to a multidisciplinary approach. Among 86 patients, 76 (88,4%) had early–diagnosed IE and 10 (11,3%) had late–diagnosed IE.Early–diagnoses IE was defined when diagnoses occurred within 30 days from first symptoms.The aim of this study was to assess the impact of ET on timeliness of diagnosis and prognosis.Comparing the two groups, in the early–diagnosed IE we found higher rate of risk factors for endocarditis and systemic embolisation (27,6% vs. 20%), with Staphylococcus and Streptococcus as the most frequent causative pathogens (43,4% and 31,5%).More frequently the late–diagnosed IE group had mechanical prosthetic valves (20% vs 7,8%) with a higher rate of cardiac surgery (80% vs 35,5%), cardiac valves complications such as abscesses, perforations and pseudo–aneurysms (20% vs 18,4%) and a higher rate of intra–hospital mortality (40% vs 18,4%). Streptococcus and Enterococcus were most involved in the late–diagnosed group.Several trials demonstrated that presence of ET reduces 1–year mortality from 18.5% to 8.2% 2 and in–hospital mortality from 28% to 13% 3. Our preliminary study confirms the importance of ET application to improve early diagnosis (88.4%) and to reduce mortality. Bibliography:1.Kouijzer et al., Native valve, prosthetic valve, and cardiac device–related infective endocarditis: A review and update on current innovative diagnostic and therapeutic strategies(2022). 2.Botelho–Nevers et al. Dramatic reduction in infective endocarditis–related mortality with a management–based approach(2009). 3.Chirillo,F.et al. Impact of a multidisciplinary management strategy on the outcome of patients with native valve infective endocarditis(2013).

Impact of Pneumococcal and Viral Pneumonia on the Respiratory and Intestinal Tract Microbiomes of Mice.

With 2.56 million deaths worldwide annually, pneumonia is one of the leading causes of death. The most frequent causative pathogens are Streptococcus pneumoniae and influenza A virus. Lately, the interaction between the pathogens, the host, and its microbiome have gained more attention. The microbiome is known to promote the immune response toward pathogens; however, our knowledge on how infections affect the microbiome is still scarce. Here, the impact of colonization and infection with S. pneumoniae and influenza A virus on the structure and function of the respiratory and gastrointestinal microbiomes of mice was investigated. Using a meta-omics approach, we identified specific differences between the bacterial and viral infection. Pneumococcal colonization had minor effects on the taxonomic composition of the respiratory microbiome, while acute infections caused decreased microbial complexity. In contrast, richness was unaffected following H1N1 infection. Within the gastrointestinal microbiome, we found exclusive changes in structure and function, depending on the pathogen. While pneumococcal colonization had no effects on taxonomic composition of the gastrointestinal microbiome, increased abundance of Akkermansiaceae and Spirochaetaceae as well as decreased amounts of Clostridiaceae were exclusively found during invasive S. pneumoniae infection. The presence of Staphylococcaceae was specific for viral pneumonia. Investigation of the intestinal microbiomés functional composition revealed reduced expression of flagellin and rubrerythrin and increased levels of ATPase during pneumococcal infection, while increased amounts of acetyl coenzyme A (acetyl-CoA) acetyltransferase and enoyl-CoA transferase were unique after H1N1 infection. In conclusion, identification of specific taxonomic and functional profiles of the respiratory and gastrointestinal microbiome allowed the discrimination between bacterial and viral pneumonia. IMPORTANCE Pneumonia is one of the leading causes of death worldwide. Here, we compared the impact of bacterial- and viral-induced pneumonia on the respiratory and gastrointestinal microbiome. Using a meta-omics approach, we identified specific profiles that allow discrimination between bacterial and viral causative.

Evaluation of ceftazidime/avibactam for treatment of carbapenemase-producing carbapenem-resistant Enterobacterales with OXA-48 and/or NDM genes with or without combination therapy.

BackgroundCarbapenem-resistant Enterobacterales (CRE) is an urgent public health threat of significant global concern. Few observational studies have evaluated the clinical outcomes for treatment of CRE harbouring OXA-48 or NDM genes with ceftazidime/avibactam. Previous findings showed lower 30 day mortality with ceftazidime/avibactam ranges between 8.3% and 22%.MethodThis single-centre retrospective cohort study included adult patients aged ≥18 years admitted to King Abdulaziz Medical City (KAMC) who had received ceftazidime/avibactam for at least 72 h for infections caused by CRE with genes encoding for carbapenemase production (CP-CRE).ResultsA total of 211 patients, mostly male (57%), having CP-CRE infections treated with ceftazidime/avibactam were included, with an average age of 62 years. More than 50% of patients were critically ill, for which 46% received invasive ventilation and 36% were on inotropes. The most frequent infectious disease was hospital/ventilator-acquired pneumonia with Klebsiella pneumoniae being the most frequent causative pathogen. The majority of isolates harboured OXA-48 (81%), followed by NDM ± OXA-48 (19%). The overall clinical cure and 30 day mortality was 78% and 21% respectively (stratified per gene: 79% and 21.6% for OXA-48 and 75% and 17.5% for NDM ± OXA-48).ConclusionsThis was the largest study that evaluated clinical outcomes associate with CP-CRE harbouring OXA-48 gene infections treated with ceftazidime/avibactam. Clinical cure and 30 day mortality were consistent with those of previous studies. Findings suggested that combination therapy with ceftazidime/avibactam had no direct impact on clinical outcomes for CP-CRE with OXA-48.

Modified poly(L-lysine)-based structures as novel antimicrobials for diabetic foot infections, an in-vitro study

Background: Wound infections occur as sequelae to skin trauma and cause significant hospitalizations, morbidity and mortality. Skin traumas arise more frequently in those with diabetes or cardiovascular disease and in these settings, may be chronic with poorer outcomes including lower limb amputation. Treatment of chronic wound infection is challenging due to antibiotic resistance and biofilm formation by bacteria including S. aureus and P. aeruginosa, which are among the most frequent causative pathogens. Managing these challenging infections requires new molecules and modalities. Methods: We evaluated antimicrobial and anti-biofilm activity of star-shaped poly(L-lysine) (PLL) polymers against S. aureus and P. aeruginosa strains and clinical isolates recovered from wounds including diabetic foot wounds (DFW) in a Dublin Hospital in 2019. A star-shaped PLL polypeptide series, specifically G2(8)PLL 20, G3(16)PLL 10, G4(32)PLL 5 with variation in polypeptide chain length and arm-multiplicity, were compared to a linear peptide, PLL 160 with equivalent number of lysine residues. Results: All PLLs, including the linear polypeptide, were bactericidal at 1μM against S. aureus 25923 and P. aeruginosa PAO1, with log reduction in colony forming units/ml between 2.7-3.6. PLL 160 demonstrated similar killing potency against 20 S. aureus and five P. aeruginosa clinical isolates from DFW, mean log reductions: 3.04 ± 0.16 and 3.96 ± 0.82 respectively after 1 hour incubation. Potent anti-biofilm activity was demonstrated against S. aureus 25923 but for clinical isolates, low to moderate loss of biofilm viability was shown using PLL 160 and G3(16)PLL 10 at 50 μM ( S. aureus) and 200 μM ( P. aeruginosa) with high inter-isolate variability . In the star-shaped architecture, antimicrobial activity was retained with incorporation of 5-mer hydrophobic amino-acid modifications to the arms of the polypeptides (series G3(16)PLL 20-coPLT 5, G3(16)PLL 20-coPLI 5, G3(16)PLL 20-coPLP 5). Conclusion: These polypeptides offer structural flexibility for clinical applications and have potential for further development, particularly in the setting of diabetic foot and other chronic wound infections.

Clinical Efficacy Protocol of Yinhuapinggan Granules: A Randomized, Double-Blind, Parallel, and Controlled Clinical Trial Program for the Intervention of Community-Acquired Drug-Resistant Bacterial Pneumonia as a Complementary Therapy.

Background: Community-acquired bacterial pneumonia (CABP) is an important health care concern in the worldwide, and is associated with significant morbidity, mortality, and health care expenditure. Streptococcus pneumoniae is the most frequent causative pathogen of CABP. Common treatment for hospitalized patients with CABP is empiric antibiotic therapy using β-lactams in combination with macrolides, respiratory fluoroquinolones, or tetracyclines. However, overuse of antibiotics has led to an increased incidence of drug-resistant S. pneumoniae, exacerbating the development of community-acquired drug-resistant bacterial pneumonia (CDBP) and providing a challenge for physicians to choose empirical antimicrobial therapy. Methods: Traditional Chinese medicine (TCM) is widely used as a complementary treatment for CDBP. Yinhuapinggan granules (YHPG) is widely used in the adjuvant treatment of CDBP. Experimental studies and small sample clinical trials have shown that YHPG can effectively reduce the symptoms of CDBP. However, there is a lack of high-quality clinical evidence for the role of YHPG as a complementary drug in the treatment of CDBP. Here, we designed a randomized, double-blind, placebo-controlled clinical trial to explore the efficacy and safety of YHPG. A total of 240 participants will be randomly assigned to the YHPG or placebo group in a 1:1 ratio. YHPG and placebo will be added to standard treatment for 10 days, followed by 56 days of follow-up. The primary outcome is the cure rate of pneumonia, and the secondary outcomes includes conversion rate of severe pneumonia, lower respiratory tract bacterial clearance, lactic acid (LC) clearance rate, temperature, C-reactive protein (CRP), criticality score (SMART-COP score), acute physiological and chronic health assessment system (APACHEII score) and clinical endpoint events. Adverse events will be monitored throughout the trial. Data will be analyzed according to a pre-defined statistical analysis plan. This research will disclose the efficacy of YHPG in acquired drug-resistant pneumonia. Clinical Trial Registration: https://clinicaltrials.gov, identifier ChiCTR2100047501

Causative Agents of Ventilator-Associated Pneumonia and Resistance to Antibiotics in COVID-19 Patients: A Systematic Review

Patients with coronavirus disease 2019 (COVID-19) have an increased risk of ventilator-associated pneumonia (VAP). This systematic review updates information on the causative agents of VAP and resistance to antibiotics in COVID-19 patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/MEDLINE, and LILACS databases from December 2019 to December 2021. Studies that described the frequency of causative pathogens associated with VAP and their antibiotic resistance patterns in critically ill COVID-19 adult patients were included. The Newcastle-Ottawa Quality Assessment Scale was used for critical appraisal. The data are presented according to the number or proportions reported in the studies. A total of 25 articles were included, involving 2766 VAP cases in COVID-19 patients (range 5–550 VAP cases). Most of the studies included were carried out in France (32%), Italy (20%), Spain (12%) and the United States (8%). Gram-negative bacteria were the most frequent causative pathogens of VAP (range of incidences in studies: P. aeruginosa 7.5–72.5%, K. pneumoniae 6.9–43.7%, E. cloacae 1.6–20% and A. baumannii 1.2–20%). S. aureus was the most frequent Gram-positive pathogen, with a range of incidence of 3.3–57.9%. The median incidence of Aspergillus spp. was 6.4%. Few studies have recorded susceptibility patterns among Gram-negative causative pathogens and have mainly reported extended-spectrum beta-lactamase (ESBL), AmpC, and carbapenem resistance. The median frequency of methicillin resistance among S. aureus isolates was 44.4%. Our study provides the first comprehensive description of the causative agents and antibiotic resistance in COVID-19 patients with VAP. Gram-negative bacteria were the most common pathogens causing VAP. Data on antibiotic resistance patterns in the published medical literature are limited, as well as information about VAP from low- and middle-income countries.

Prognostic factors of severe pneumonia in patients treated with rituximab in the intensive care unit.

ObjectiveThe aim of this study was to describe the clinical characteristics and prognostic factors of patients treated with rituximab (RTX) who developed severe pneumonia in the intensive care unit (ICU).MethodsWe systematically reviewed the medical records of 40 patients who received RTX and developed severe pneumonia in the ICU at our hospital from January 2009 to January 2019 to evaluate the underlying conditions, clinical course, and possible prognostic factors.ResultsMost patients had underlying hematologic malignancies (n = 21, 52.5%), followed by rheumatologic diseases (n = 17, 42.5%). The most frequent causative pathogens were fungi (n = 11, 27.5%), followed by bacteria (n = 9, 22.5%) and Pneumocystis jirovecii pneumonia (n = 8, 20%). Thirty patients (75%) died, and the other 10 patients (25%) survived. Compared with survivors, patients who died were significantly older (60.6 ± 10.6 vs 44.4 ± 18.3 years) and had chronic lung disease (40% vs 0%).ConclusionOlder age and chronic lung disease were significantly associated with mortality in patients treated with RTX.

Oral levofloxacin: population pharmacokinetics model and pharmacodynamics study in bone and joint infections.

This study aimed at characterizing the pharmacokinetics (PK) of oral levofloxacin in adult patients in order to optimize dosing scheme and explore the PK/pharmacodynamics (PD) of levofloxacin in bone and joint infections (BJIs). From November 2015 to December 2019, all patients hospitalized in Cochin Hospital, treated with levofloxacin and who had at least one dosage for therapeutic drug monitoring were included. PK was described using non-linear mixed-effect modelling. In a subgroup of patients with BJIs, the association between PK, MIC for the isolated pathogen and clinical outcome was investigated. Monte Carlo simulations investigated dosing regimens to achieve the PK/PD target (AUC/MIC ratio >100). One hundred and two patients were included (199 measurements), including 32 treated for BJI. A one-compartment model with first-order absorption and elimination best described the data. Effects of estimated creatinine clearance (eCLCR) and age were significant on levofloxacin clearance. In BJI patients, no significant association was found between levofloxacin PK/microbiological parameters and either clinical outcome or adverse events. Based on our model, we proposed optimized oral levofloxacin dosing regimens according to renal function, to reach the PK/PD target AUC/MIC ratio >100 for three frequent causative pathogens (Staphylococcus aureus, Enterobacterales and Pseudomonas aeruginosa). Our results reinforce the need of determining the MIC and using therapeutic drug monitoring in complex infections caused by P. aeruginosa.

Establishment and validation of a nomogram to predict the in-hospital death risk of nosocomial infections in cancer patients

BackgroundAttributed to the immunosuppression caused by malignancy itself and its treatments, cancer patients are vulnerable to developing nosocomial infections. This study aimed to develop a nomogram to predict the in-hospital death risk of these patients.MethodsThis retrospective study was conducted at a medical center in Northwestern China. The univariate and multivariate logistic regression analyses were adopted to identify predictive factors for in-hospital mortality of nosocomial infections in cancer patients. A nomogram was developed to predict the in-hospital mortality of each patient, with receiver operating characteristic curves and calibration curves being generated to assess its predictive ability. Furthermore, decision curve analysis (DCA) was also performed to estimate the clinical utility of the nomogram.ResultsA total of 1,008 nosocomial infection episodes were recognized from 14,695 cancer patients. Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (15.5%) was the most predominant causative pathogen. Besides, multidrug-resistant strains were discovered in 25.5% of cases. The multivariate analysis indicated that Eastern Cooperative Oncology Group Performance Status 3–4, mechanical ventilation, septic shock, hypoproteinemia, and length of antimicrobial treatment < 7 days were correlated with higher in-hospital mortality. Patients who received curative surgery were correlated with favorable survival outcomes. Ultimately, a nomogram was constructed to predict the in-hospital mortality of nosocomial infections in cancer patients. The area under the curve values of the nomogram were 0.811 and 0.795 in the training and validation cohorts. The calibration curve showed high consistency between the actual and predicted in-hospital mortality. DCA indicated that the nomogram was of good clinical utility and more credible net clinical benefits in predicting in-hospital mortality.ConclusionsNosocomial infections stay conjoint in cancer patients, with gram-negative bacteria being the most frequent causative pathogens. We developed and verified a nomogram that could effectively predict the in-hospital death risk of nosocomial infections among these patients. Precise management of high-risk patients, early recognition of septic shock, rapid and adequate antimicrobial treatment, and dynamic monitoring of serum albumin levels may improve the prognosis of these individuals.

Modified poly(L-lysine)-based structures as novel antimicrobials for diabetic foot infections, an in-vitro study.

Background: Wound infections occur as sequelae to skin trauma and cause significant hospitalizations, morbidity and mortality. Skin traumas arise more frequently in those with diabetes or cardiovascular disease and in these settings, may be chronic with poorer outcomes including lower limb amputation. Treatment of chronic wound infection is challenging due to antibiotic resistance and biofilm formation by bacteria including S. aureus and P. aeruginosa, which are among the most frequent causative pathogens. Managing these challenging infections requires new molecules and modalities. Methods: We evaluated antimicrobial and anti-biofilm activity of star-shaped poly(L-lysine) (PLL) polymers against S. aureus and P. aeruginosa strains and clinical isolates recovered from wounds including diabetic foot wounds (DFW) in a Dublin Hospital in 2019. A star-shaped PLL polypeptide series, specifically G2(8)PLL 20, G3(16)PLL 10, G4(32)PLL 5 with variation in polypeptide chain length and arm-multiplicity, were compared to a linear peptide, PLL 160 with equivalent number of lysine residues. Results: All PLLs, including the linear polypeptide, were bactericidal at 1μM against S. aureus 25923 and P. aeruginosa PAO1, with log reduction in colony forming units/ml between 2.7-3.6. PLL 160 demonstrated similar killing potency against 20 S. aureus and five P. aeruginosa clinical isolates from DFW, mean log reductions: 3.04 ± 0.16 and 3.96 ± 0.82 respectively after 1 hour incubation. Potent anti-biofilm activity was demonstrated against S. aureus 25923 but for clinical isolates, low to moderate loss of biofilm viability was shown using PLL 160 and G3(16)PLL 10 at 50 μM ( S. aureus) and 200 μM ( P. aeruginosa) with high inter-isolate variability . In the star-shaped architecture, antimicrobial activity was retained with incorporation of 5-mer hydrophobic amino-acid modifications to the arms of the polypeptides (series G3(16)PLL 20-coPLT 5, G3(16)PLL 20-coPLI 5, G3(16)PLL 20-coPLP 5). Conclusion: These polypeptides offer structural flexibility for clinical applications and have potential for further development, particularly in the setting of diabetic foot and other chronic wound infections.

High genetic heterogeneity of Mycobacterium intracellulare isolated from respiratory specimens

BackgroundM. intracellulare is a frequent causative pathogen of nontuberculous mycobacteria infection that causes infections in the respiratory tract, whose incidence is increasing in many countries. This study aimed at determining the VNTR-based genetic diversity of a collection of 39 M. intracellulare human strains isolated from respiratory specimens over the last 5 years.ResultsThe VNTR analysis showed that M. intracellulare strains displayed a high genetic diversity, indicating that the M. intracellulare genotypes are quite heterogeneous in our geographical area. Moreover, a comparison with VNTR profiles of strains from other countries confirmed that genotypes of clinical strains of M. intracellulare are not related to geographical origin.ConclusionsVNTR typing has proved to be a highly discriminatory method for better understanding the molecular epidemiology of M. intracellulare.

Clinical characteristics of pediatric febrile urinary tract infection in Japan

BackgroundFebrile urinary tract infection (fUTI) is the most common serious bacterial infection in children. Despite this, there have been no studies examining the clinical features of pediatric fUTI in Japan. The purpose of this study was to describe the clinical characteristics of fUTI in Japanese children. MethodsA multicenter, retrospective, observational study was conducted at 21 hospitals in Japan. Children under the age of 15 years who were diagnosed with fUTI between 2008 and 2017 were included. The diagnostic criteria were a temperature over 38 °C and the presence of a single bacterial pathogen in urine culture. Patient characteristics were obtained from medical records. ResultsIn total, 2,049 children were included in the study. The median age was 5 months, and 59.3% were male. It was found that 87.0% of the males and 53.2% of the females were under 1 year of age. The main causative pathogens identified were Escherichia coli and Enterococcus spp., accounting for 76.6% and 9.8% of infections, respectively. ConclusionsThere was a male predominance of fUTI in Japanese children, particularly in infants. Enterococcus spp. were the second most frequent causative pathogen; therefore, Gram staining of urine samples is strongly recommended before initiating antibiotic therapy.

Trends in the Epidemiology of Candidemia in Intensive Care Units From 2006 to 2017: Results From the Korean National Healthcare-Associated Infections Surveillance System.

Candidemia is an important healthcare-associated infection (HAI) in intensive care units (ICUs). However, limited research has been conducted on candidemia in the Republic of Korea. We aimed to analyze the secular trends in the incidence and distribution of candidemia in ICUs over 12-years using data from the Korean National Healthcare-Associated Infections Surveillance System (KONIS). KONIS was established in 2006 and has performed prospective surveillance of HAIs including bloodstream infections (BSIs) in ICUs. We evaluated the trends in the distribution of causative pathogens and the incidence of candidemia. From 2006 to 2017, 2,248 candidemia cases occurred in 9,184,264 patient-days (PDs). The pooled mean incidence rates of candidemia significantly decreased from 3.05 cases/10,000 PDs in 2006 to 2.5 cases/10,000 PDs in 2017 (P = 0.001). Nevertheless, the proportion of candidemia gradually increased from 15.2% in 2006 to 16.6% in 2017 (P = 0.001). The most frequent causative pathogen of BSIs from 2006 to 2012 was Staphylococcus aureus; however, Candida spp. emerged as the most frequent causative pathogen since 2013. C. albicans (39.9%) was the most common among Candida spp. causing BSIs, followed by Candida tropicalis (20.2%) and Candida parapsilosis (18.2%). The proportion of candidemia caused by C. glabrata significantly increased from 8.9% in 2006 to 17.9% in 2017 (P < 0.001). There was no significant change in the distribution of Candida spp. by year (P = 0.285). The most common source of BSIs was central lines associated BSI (92.5%). There was a significant increase in the proportion of candidemia by year in hospitals with organ transplant wards (from 18.9% in 2006 to 21.1% in 2017, P = 0.003), hospitals with <500 beds (from 2.7% in 2006 to 13.6% in 2017, P < 0.001), and surgical ICUs (from 16.2% in 2006 to 21.7% in 2017, P = 0.003). The proportion of candidemia has increased in Korea, especially in hospitals with <500 beds and surgical ICUs. Thus, appropriate infection control programs are needed.

Co-infection with Staphylococcus aureus after primary influenza virus infection leads to damage of the endothelium in a human alveolus-on-a-chip model

Pneumonia is one of the most common infectious diseases worldwide. The influenza virus can cause severe epidemics, which results in significant morbidity and mortality. Beyond the virulence of the virus itself, epidemiological data suggest that bacterial co-infections are the major cause of increased mortality. In this context, Staphylococcus aureus represents a frequent causative bacterial pathogen. Currently available models have several limitations in the analysis of the pathogenesis of infections, e.g. some bacterial toxins strongly act in a species-specific manner. Human 2D mono-cell culture models often fail to maintain the differentiation of alveolus-specific functions. A detailed investigation of the underlying pathogenesis mechanisms requires a physiological interaction of alveolus-specific cell types. The aim of the present work was to establish a human in vitro alveolus model system composed of vascular and epithelial cell structures with cocultured macrophages resembling the human alveolus architecture and functions. We demonstrate that high barrier integrity maintained for up to 14 d in our model containing functional tissue-resident macrophages. We show that flow conditions and the presence of macrophages increased the barrier function. The infection of epithelial cells induced a high inflammatory response that spread to the endothelium. Although the integrity of the epithelium was not compromised by a single infection or co-infection, we demonstrated significant endothelial cell damage associated with loss of barrier function. We established a novel immune-responsive model that reflects the complex crosstalk between pathogens and host. The in vitro model allows for the monitoring of spatiotemporal spreading of the pathogens and the characterization of morphological and functional alterations attributed to infection. The alveolus-on-a-chip represents a promising platform for mechanistic studies of host-pathogen interactions and the identification of molecular and cellular targets of novel treatment strategies in pneumonia.

A Case of Emphysematous Cystitis Presenting with Acute Urine Retention in an Immunocompetent Host

Emphysematous cystitis is a very rare form of lower urinary tract infection with gas formation. It commonly presents with suprapubic pain associated with lower urinary tract symptoms (LUTS). Predisposing factors are old age, diabetes mellitus, female gender, urinary tract obstruction and neurogenic bladder. Most frequent causative pathogens are Escherichia coli and Klebsiella pneumonia. Imaging is essential to confirm the diagnosis. Prompt treatment marks in improved outcome and better prognosis. It should be considered as one of the differentials of acute urinary retention with UTI. Here we present a case of emphysematous cystitis in an immunocompetent host presenting as acute urinary retention.

Analysis of Klebsiella as a Prognostic Factor of Ocular Outcomes in Endogenous Endophthalmitis with Decision Tree Analysis.

BackgroundEndogenous endophthalmitis (EE) is a fulminant ocular disease. This study was conducted to explore frequent pathogens and significant prognostic factors associated with poor ocular outcomes.Materials and MethodsA retrospective analysis was performed in a tertiary hospital in Korea. Thirty-nine patients, treated between January 2000 and June 2017, were eligible for the analysis. Ocular outcomes were classified as follows: 1) no light perception (NLP), 2) light perception (LP), 3) hand motion (HM), 4) counting fingers (CF), and 5) 20/200 or better. Logistic regression and decision tree analyses were used to identify risk factors that were associated with poor outcomes.ResultsPathogens were identified in 23 (58.9%) samples from blood, liver aspirate, and/or vitreous humor. Klebsiella pneumoniae was the most frequent organism (12/39, 30.8%), followed by Candida species (3/39, 8.3%). The most common combined infection was liver abscess (16/39, 41.0%). Acute pyelonephritis occurred in 30.8% of cases (12/39). Final ocular outcomes were as follows: 35.9% (14/39) NLP, 15.4% (6/39) LP, 15.4% (6/39) HM, 7.7% (3/39) CF, and 25.6% (10/39) 20/200 or better. K. pneumoniae was a poor prognostic factor in univariate (odds ratio [OR], 13.3; 95% confidence interval [CI], 2.1-130.9) and multivariate (OR, 17.5; 95% CI, 2.1-398.8) regression analyses (NLP and LP vs. HM, CF, and 20/200 or better). Other factors did not reach statistical difference. Decision tree analysis identified K. pneumoniae as a node that divided ocular outcomes (P = 0.017).ConclusionsIn conclusion, K. pneumoniae is the most frequent causative pathogen of EE. Considering the poor prognosis and rapid progression of K. pneumoniae EE, physicians should test for K. pneumoniae EE in patients who experience acute systemic infections with ocular signs and symptoms.

Determination of Pathogens in Postoperative Wound Infection After Surgically Reduced Calcaneal Fractures and Implications for Prophylaxis and Treatment

High rates of postoperative wound infection (POWI) have been reported after surgery for calcaneal fractures. This is a retrospective cohort study to determine the causative pathogens of these infections and subsequent treatment strategies. In addition, microbacterial growth from superficial wound swabs and deep fluid or tissue cultures were compared. Patients with a unilateral surgically treated calcaneal fracture during a 15-year period were included. Patient, fracture, and surgical characteristics were collected from the electronic medical records. An infection was categorized as deep or superficial using the Centers for Disease Control and Prevention criteria. Secondary outcomes were wound edge necrosis and wound dehiscence. The collection of culture swabs, their results, and treatment strategies were documented. Of 357 patients, 92 (26%) developed a POWI; 55 (60%) deep and 37 (40%) superficial. The most frequent causative pathogens were Enterobacteriaceae and Staphylococcus aureus. Of the 55 patients with deep infection, 31 (56%) were treated with intravenous antibiotics and surgical debridement, 2 (4%) with intravenous antibiotics, and 22 (40%) with implant removal. In 33 of 92 patients (36%) with a POWI, both superficial and deep cultures were obtained, with a microorganism not cultured from the superficial swab 13 (39%) times. In conclusion, we found that one quarter of patients with operative calcaneal fracture treatment developed a POWI, mainly caused by Enterobacteriaceae or S. aureus. Physicians should not rely on the results of superficially obtained cultures for adequate treatment of deep infection. Because the spectrum of sensitivity profiles varies greatly between hospitals and countries, we recommend empiric antibiotic treatment of both gram-positive and gram-negative microorganisms on suspicion of deep infection.

Epidemiology and outcomes of Endophthalmitis in chronic dialysis patients: a 13-year experience in a tertiary referral center in Taiwan

BackgroundEndophthalmitis is a severe eye infection leading to disabling outcome. Because there were only a few case report illustrating endophthalmitis in chronic dialysis patient, we would like to investigate the epidemiology and clinical features of endophthalmitis in chronic dialysis patient in a tertiary referral center.MethodsWe searched the health information system in the study hospital with ICD9 encoding endophthalmitis during Jan. 2002 to Dec. 2015. A total of 32 episodes of endophthalmitis occurred in chronic dialysis patients. We performed an 1:2 case-control match on propensity score. The demographic features, clinical manifestation, infection focus and visual outcome were recorded.ResultsOf the total of 32 patients, 25 were classified as endogenous endophthalmitis and another seven were exogenous. Most patients presented with ophthalmalgia (n = 32, 100%) and periocular swelling (n = 31, 96.8%), whereas half of the patients suffered blurred vision (n = 16, 50%). Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequent causative pathogens. Dialysis vascular infection was also a possible unique focus for bacteremia. The visual acuity of the endogenous groups were less likely to improve in the chronic dialysis patients compared with control group.ConclusionThis is the first and the largest case series focusing on endophthalmitis in chronic dialysis patients. Our study showed different pathogen spectrum, an unique bacterial origin and worse visual outcome in these group of patients. Prompt referral to ophthalmologists when the patients present with suspicious symptoms (blurred vision, ophthalmalgia and periocular swelling) is crucial.