Efficacy of cefoperazone/sulbactam for ESBL-producing Escherichia coli and Klebsiella pneumoniae bacteraemia and the factors associated with poor outcomes.

OBJECTIVE: We aimed to assess the efficacy of cefoperazone/sulbactam (CPZ/SUL) in extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales infections and identify factors influencing outcomes. METHODS: This retrospective multicentre study was conducted in Taiwan (January 2015 to December 2020) and examined the efficacy of CPZ/SUL treatment in ESBL-producing Enterobacterales bacteraemia. The minimum inhibitory concentrations (MICs) were determined using agar dilution; ESBL/AmpC genes were detected using polymerase chain reaction. The primary outcome was clinical success, whereas the secondary outcome was 30-day mortality. Clinical success was defined as the complete resolution of clinical signs and symptoms of K. pneumoniae or E. coli infection, with no evidence of persistent or recurrent bacteraemia. The factors influencing outcomes were identified using a multivariate analysis. RESULTS: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia, with a 30-day mortality rate of 9.1% (10/110). Among 110 ESBL-producing isolates, a high clinical success rate was observed at an MIC of ≤32/32 mg/L. Multivariate analysis revealed that a Charlson comorbidity index (CCI) of ≥6 was associated with lower clinical success [odds ratio (OR): 5.80, 95% confidence interval (CI): 1.15-29.14, P = 0.033]. High Sequential Organ Failure Assessment scores (≥6) were significantly associated with increased 30-day mortality (OR: 14.34, 95% CI: 1.45-141.82, P = 0.023). DISCUSSION: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia. Treatment success was evident when the CPZ and SUL MIC was ≤32/32 mg/L. Comorbidities (CCI ≥6) were associated with lower clinical success, while disease severity (Sequential Organ Failure Assessment score ≥6) correlated with higher mortality.

Increasing trend of healthcare-associated infections due to vancomycin-resistant Enterococcus faecium (VRE-fm) paralleling escalating community-acquired VRE-fm infections in a medical center implementing strict contact precautions: An epidemiologic and pathogenic genotype analysis and its implications.

OBJECTIVE: To clarify whether there were clandestine intra-hospital spreads of vancomycin-resistant Enterococcus faecium (VRE-fm) isolates that led to specific strain of VRE lingering in the hospital and/or developing outbreaks that rendered a progressively increasing trend of healthcare-associated infections due to VRE-fm (VRE-fm-HAIs). SETTING: Despite implementing strict contact precautions for hospitalized patients with VRE-fm-infection/colonization, number of VRE-fm-HAIs in a medical centre in southern Taiwan were escalating in 2009-2019, paralleling an increasing trend of community-acquired VRE-fm- infections. METHODS: We analyzed epidemiologic data and genotypes of non-duplicate VRE-fm isolates each grown from a normally sterile site of 89 patients between December 2016 and October 2018; multilocus sequence typing (MLST) and pulse-field gel electrophoresis (PFGE) typing were performed. RESULTS: Totally 13 sequence types (STs) were found, and the 3 leading STs were ST17 (44％), ST78 (37％), and ST18 (6％); 66 pulsotypes were generated by PFGE. Four VRE-fm isolates grouped as ST17/pulsotype S, 2 as ST17/pulsotype AS, 2 as ST17/pulsotype AU, and 3 as ST78/pulsotype V grew from clinical specimens sampled less than one week apart from patients staying at different wards/departments and/or on different floors of the hospital. CONCLUSIONS: Despite possible small transitory clusters of intra-hospital VRE-fm spreads, there was no specific VRE-fm strain lingering in the hospital leading to increasing trend of VRE-fm-HAIs during the study period. Strict contact precautions were able to curb intra-hospital VRE-fm spreads, but unable to curb the increasing trend of VRE-fm-HAIs with the backdrop of progressively increasing VRE-fm-infections/colorizations in the community.

Correlation Between Cefoperazone/Sulbactam MIC Values and Clinical Outcomes of Escherichia coli Bacteremia.

INTRODUCTION: The clinical efficiency of cefoperazone/sulbactam (CPZ/SUL) against Escherichia coli bacteremia was unknown. This study aimed to explore the relationship between CPZ/SUL MIC values and clinical outcomes in Escherichia coli bacteremia. METHODS: A multicenter, retrospective, observational cohort study was conducted in Taiwan between January 2015 and December 2020. Patients treated with CPZ/SUL for E. coli bacteremia were enrolled in the analysis. The CPZ/SUL MICs were determined by using the agar dilution method. The primary outcome was 30-day mortality. RESULTS: Among 247 isolates, 160 (64.8%) isolates were susceptible, 8 (3.2%) were intermediate, and 79 (32.0%) were resistant to cefoperazone. The activity of cefoperazone against cefoperazone-non-susceptible E. coli (n = 87) was restored upon combination with sulbactam, with susceptibility ranging from 0% to 97.7%. The 30-day mortality was 4.5% (11/247) and overall clinical success rate was 91.9% (227/247). Multivariate Cox proportional-hazards model revealed that heart failure [adjusted relative risk (ARR), 5.49; 95% confidence interval (CI) 1.31-23.02; p = 0.020], malignancy (ARR 7.50; 95% CI 2.02-27.80; p = 0.003), SOFA score (ARR 1.29; 95% CI 1.09-1.52; p = 0.003), and CPZ/SUL MIC ≥ 64 mg/L (ARR 11.31; 95% CI 1.34-95.52; p = 0.026) were independently associated with 30-day mortality. No statistically significant differences in 30-day mortality were found between groups with or without cefoperazone susceptibility (3.4% vs. 5.0%, p = 0.751, respectively). CONCLUSIONS: Patients with E. coli bacteremia who were treated with CPZ/SUL had a favorable outcome when the MICs of the isolates were ≤ 16 mg/L and a high risk of mortality with MICs ≥ 64 mg/L.

Genetic relatedness among azole-resistant Candida tropicalis clinical strains in Taiwan from 2014 to 2018.

To monitor trends in the distribution of yeast species and the susceptibilities of these species to commonly prescribed antifungal drugs, we conduct the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) every 4 years. We found that 25 of 294 Candida tropicalis isolates from TSARY 2014 and 31 of 314 C. tropicalis isolates from TSARY 2018 were resistant to fluconazole. We determined the genetic relatedness among fluconazole-resistant C. tropicalis isolates by multilocus sequence typing (MLST). Among 174 C. tropicalis isolates, including all 56 fluconazole-resistant, all 26 susceptible-dose dependent and 92 selected fluconazole-susceptible isolates, 59 diploid sequence types (DSTs) were identified. We found that 22 of the 25 fluconazole-resistant C. tropicalis from TSARY 2014 and 29 of the 31 fluconazole-resistant C. tropicalis from TSARY 2018 were genetically related and belonged to the same cluster (clade 4). A combination of mutation and overexpression of ERG11, encoding the target of azole drugs, was the major mechanism contributing to drug resistance. Approximately two-thirds of reviewed patients infected or colonised by fluconazole-resistant C. tropicalis were azole-naïve. Furthermore, there was no evidence of patient-to-patient transmission. Because the clade 4 fluconazole-resistant C. tropicalis strain persists in Taiwan, it is important to identify the source of azole-resistant C. tropicalis to prevent the spread of this resistant strain.

An observational study on prevalence of latent tuberculosis infection and outcome of 3HP treatment in patients under hemodialysis in Taiwan.

BACKGROUND: Identification and treatment for latent tuberculosis infection (LTBI) are of great epidemiological importance of controlling tuberculosis (TB) worldwide. Identification in high-risk population on dialysis and treatment with 12-week weekly rifapentine plus isoniazid (3HP) help improve prevention outcomes effectively. METHODS: We conducted a single-center, nonrandomized follow-up study on end-stage renal disease patients on hemodialysis. The interferon-gamma release assay (IGRA) was used for the diagnosis of LTBI. Participants were treated with 3HP, and treatment responses were recorded and analyzed. RESULTS: A total of 123 of the 641 patients showed positive IGRA results. The male sex, age >60 years, low serum albumin level (<4.0 g/dL), and hypercalcemia (serum calcium level > 10.2 mg/dL) were associated with IGRA positivity. Seventy-five patients were treated with 3HP, with a completion rate of 66.67%. The male sex, albumin level >4.0 g/dL, and absence of adverse drug reaction were associated with increased completion rates. Adverse drug reactions included dizziness, fatigue, nausea and vomiting, fever, and hypertension. CONCLUSION: Risk factors for LTBI in dialysis patients were identified to prioritize LTBI screening and initiate early treatment. The completion rate in dialysis patients were approximately 2 of 3 patients with mild adverse drug reaction, leading to discontinuation of the treatment.

Epidemiological Correlation of Pulmonary Aspergillus Infections with Ambient Pollutions and Influenza A (H1N1) in Southern Taiwan.

An increase in fungal spores in ambient air is reported during a spike in particulate matter (PM2.5 and PM10) aerosols generated during dust or smog events. However, little is known about the impact of ambient bioaerosols on fungal infections in humans. To identify the correlation between the incidence of pulmonary aspergillosis and PM-associated bioaerosols (PM2.5 and PM10), we retrospectively analyzed data between 2015 and 2018 (first stage) and prospectively analyzed data in 2019 (second stage). Patient data were collected from patients in three medical institutions in Tainan, a city with a population of 1.88 million, located in southern Taiwan. PM data were obtained from the Taiwan Air Quality Monitoring Network. Overall, 544 non-repeated aspergillosis patients (first stage, n = 340; second stage, n = 204) were identified and enrolled for analysis. The trend of aspergillosis significantly increased from 2015 to 2019. Influenza A (H1N1) and ambient PMs (PM2.5 and PM10) levels had significant effects on aspergillosis from 2015 to 2018. However, ambient PMs and influenza A (H1N1) in Tainan were correlated with the occurrence of aspergillosis in 2018 and 2019, respectively. Overall (2015-2019), aspergillosis was significantly correlated with influenza (p = 0.002), influenza A (H1N1) (p < 0.001), and PM2.5 (p = 0.040) in Tainan City. Using a stepwise regression model, influenza A (H1N1) (p < 0.0001) and Tainan PM10 (p = 0.016) could significantly predict the occurrence of aspergillosis in Tainan. PM-related bioaerosols and influenza A (H1N1) contribute to the incidence of pulmonary aspergillosis.

Increased financial burdens and lengths of stay in patients with healthcare-associated infections due to multidrug-resistant bacteria in intensive care units: A propensity-matched case-control study.

BACKGROUND AND OBJECTIVES: Incidence rates of healthcare-associated infections (HAIs) depend upon infection control policy and practices, and the effectiveness of the implementation of antibiotic stewardship. Amongst intensive care unit (ICU) patients with HAIs, a substantial number of pathogens were reported to be multidrug-resistant bacteria (MDRB). However, impacts of ICU HAIs due to MDRB (MDRB-HAIs) remain understudied. Our study aimed to evaluate the negative impacts of MRDB-HAIs versus HAIs due to non-MDRB (non-MRDB-HAIs). METHODS: Among 60,317 adult patients admitted at ICUs of a 2680-bed medical centre in Taiwan between January 2010 and December 2017, 279 pairs of propensity-score matched MRDB-HAI and non-MRDB-HAI were analyzed. PRINCIPAL FINDINGS: Between the MDRB-HAI group and the non-MDRB-HAI group, significant differences were found in overall hospital costs, costs of medical and nursing services, medication, and rooms/beds, and in ICU length-of-stay (LOS). As compared with the non-MDRB-HAI group, the mean of the overall hospital costs of patients in the MDRB-HAI group was increased by 26%; for categorized expenditures, the mean of costs of medical and nursing services of patients in the MDRB-HAI group was increased by 8%, of medication by 26.9%, of rooms/beds by 10.3%. The mean ICU LOS in the MDRB-HAI group was increased by 13%. Mortality rates in both groups did not significantly differ. CONCLUSIONS: These data clearly demonstrate more negative impacts of MDRB-HAIs in ICUs. The quantified financial burdens will be helpful for hospital/government policymakers in allocating resources to mitigate MDRB-HAIs in ICUs; in case of need for clarification/verification of the medico-economic burdens of MDRB-HAIs in different healthcare systems, this study provides a model to facilitate the evaluations.

Diabetic patients suffering dengue are at risk for development of dengue shock syndrome/severe dengue: Emphasizing the impacts of co-existing comorbidity(ies) and glycemic control on dengue severity.

BACKGROUND/PURPOSE: The impact of type 2 diabetes mellitus (DM2) on clinical severity of dengue has not been fully understood. We aimed to assess risk factors for dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) and severe dengue (SD) (defined based on the World Health Organization 1997 and 2009 dengue classifications), and additionally identify, among DM2 patients, who are at risk for developing DHF/DSS and severe dengue. METHODS: A retrospective analysis of dengue patients diagnosed between 2002 and 2010. Risk factors for development of DHF/DSS/SD were identified using multivariate analysis. To elucidate the impacts of coexisting comorbidity(ies) (i.e., hypertension, chronic kidney disease, old stroke, and/or ischemic heart disease) and glycemic control on clinical outcomes of dengue in DM2 patients, the overall DM2 patients and stratified DM2 patients (HbA1c < 7% vs. HbA1c â‰§ 7%), with or without comorbidity(ies), were separately compared to controls (patients without any morbidity). RESULTS: Of 767 (146 DM2 and 621 controls) included patients, 1.4% suffered DSS and 3.3% SD. While DM2 was an independent risk factor for DSS (adjusted odds ratio [AOR] = 7.473; 95% confidence interval [CI] = 2.221-25.146) and SD (AOR = 6.207; 95% CI = 2.464-15.636), only DM2 patients with additional comorbidity(ies) and suboptimal glycemic control (HbA1c â‰§ 7%) had significantly higher incidences of non-shock DHF (60.8% vs. 29%), DSS (8.7% vs. 0.8%) and SD (34.8% vs. 1.1%). CONCLUSIONS: These data could help narrow down the number of targets in the triage for risky DM2 dengue patients to those with suboptimal glycemic control and co-existing comorbidity(ies).

Determining the clinical characteristics and prognostic factors for the outcomes of Japanese encephalitis in adults: A multicenter study from southern Taiwan.

BACKGROUND: In Southeast Asia, Japanese encephalitis (JE) is an important cause of viral encephalitis which may cause severe neurological sequelae. JE affects mostly children; therefore, clinical presentations and prognosis of adult JE patients are seldom addressed. This study aimed to describe the clinical characteristics and prognostic factors for the outcome of adult JE patients. METHODS: Medical records of adult JE patients with acute encephalitis syndrome during 2001-2018 from five medical centers in southern Taiwan were reviewed. Clinical characteristics, brain images, and prognostic factors for outcomes were analyzed. Patients were divided into the good outcome (GO) group and poor outcome (PO) group according to their Glasgow Coma Scale (GCS) scores (GCS >8 vs. ≤ 8) at discharge. RESULTS: Sixty-eight patients (men, 61.8%; median age, 50 years) were included. Summer is the epidemic season, and the number of cases peaked in June. The most common symptoms at initial presentation were altered consciousness and fever (both 94.1%), followed by headache (51.4%). The most commonly involved brain regions were thalamus (55.7%) and basal ganglion (37.7%). The median GCS score at nadir was 8, and the median time from onset to nadir was five days. Fifty-two patients were included in the GO group, while 16 were included in the PO group. On multivariate analysis, flaccidity, rigidity, and elevated CSF protein level were identified as independent prognostic factors for PO. CONCLUSION: Initial clinical presentations of abnormal muscle tone including flaccidity, rigidity and high CSF protein levels are independent prognostic factors for PO in adult JE patients.

Randomized Noninferiority Trial of Cefoperazone-Sulbactam versus Cefepime in the Treatment of Hospital-Acquired and Healthcare-Associated Pneumonia.

Cefoperazone, a third-generation cephamycin with broad-spectrum antibacterial activity and the ability to permeate bacterial cell membranes, is active against commonly encountered multidrug-resistant pathogens for hospital-acquired pneumonia (HAP) and health care-associated pneumonia (HCAP). To clarify the clinical effects of cefoperazone-sulbactam in the treatment of HAP and HCAP, we conducted an open-label, randomized, noninferiority trial that recruited patients aged ≥18 years suffering HAP/HCAP. Participants were randomly assigned to the cefoperazone-sulbactam (2 g of each per 12 h) or cefepime (2 g per 12 h) arm. Clinical and microbiological responses were evaluated at early posttherapy and test-of-cure visits. Recruited patients were allocated to subpopulations for intent-to-treat (n = 154), per-protocol (n = 147), and safety (n = 166) analyses. Intent-to-treat analysis demonstrated that (i) at the early posttherapy visit, 87.3% of patients receiving cefoperazone-sulbactam and 84.3% of patients receiving cefepime achieved clinical improvement or cure (risk difference of 3.0%; 95% confidence interval [CI], -9.0% to 15.0%), and (ii) at the test-of-cure visit, 73.1% of patients receiving cefoperazone-sulbactam and 56.8% of patients receiving cefepime were assessed as cured (risk difference of 16.3%; 95% CI, 0.0% to 33.0%). These results indicated the noninferiority of cefoperazone-sulbactam to cefepime, which was confirmed by per-protocol analysis. The chest radiographic consolidation/infiltration resolution rate, microbiological eradiation rate, and percentage of adverse events were comparable in both groups. Serious adverse events were rare, and none was judged to be related to the study drugs. Cefoperazone-sulbactam at 2 g every 12 h was noninferior to cefepime at 2 g every 2 h for patients with HCAP.

Viridans streptococcus peritonitis in peritoneal dialysis: clinical characteristics and comparison with concurrent polymicrobial infection.

BACKGROUND: The clinical course of Viridans streptococci (VS) peritonitis in patients undergoing peritoneal dialysis (PD) is rarely reported. This study examined the association of clinical factors with VS peritonitis. METHODS: We retrospectively reviewed clinical data from patients with VS peritonitis from March 1990 to February 2016 in a PD center in Taiwan and evaluated clinical profiles and treatment outcomes. RESULTS: A total of 109 episodes of VS peritonitis in 71 patients identified. Among these patients, 57 had mono-VS peritonitis and 14 had concurrent polymicrobial infections. The median time interval from PD initiation to the first VS peritonitis episode was 18 months (range, 0.6-144 months). Among clinical outcomes, most VS peritonitis episodes were completely cured regardless of a history of peritonitis. All episodes with catheter removal occurred in those without a history of recent antibiotic use. CONCLUSION: VS peritonitis in patients undergoing PD typically has favorable treatment outcomes. Antibiotic therapy should be started promptly.

Correction: The Critical Role of Early Dengue Surveillance and Limitations of Clinical Reporting - Implications for Non-Endemic Countries.

[This corrects the article DOI: 10.1371/journal.pone.0160230.].

Characteristics and predictors for gastrointestinal hemorrhage among adult patients with dengue virus infection: Emphasizing the impact of existing comorbid disease(s).

BACKGROUND: Gastrointestinal (GI) bleeding is a leading cause of death in dengue. This study aims to identify predictors for GI bleeding in adult dengue patients, emphasizing the impact of existing comorbid disease(s). METHODS: Of 1300 adults with dengue virus infection, 175 (mean age, 56.5±13.7 years) patients with GI bleeding and 1,125 (mean age, 49.2±15.6 years) without GI bleeding (controls) were retrospectively analyzed. RESULTS: Among 175 patients with GI bleeding, dengue hemorrhagic fever was found in 119 (68%) patients; the median duration from onset dengue illness to GI bleeding was 5 days. Gastric ulcer, erythematous gastritis, duodenal ulcer, erosive gastritis, and hemorrhagic gastritis were found in 52.3%, 33.3%, 28.6%, 28.6%, and 14.3% of 42 patients with GI bleeding who had undergone endoscopic examination, respectively. Overall, nine of the 175 patients with GI bleeding died, giving an in-hospital mortality rate of 5.1%. Multivariate analysis showed age ≥60 years (cases vs. controls: 48% vs. 28.3%) (odds ratio [OR]: 1.663, 95% confidence interval [CI]: 1.128-2.453), end stage renal disease with additional comorbidities (cases vs. controls: 1.7% vs. 0.2%) (OR: 9.405, 95% CI: 1.4-63.198), previous stroke with additional comorbidities (cases vs. controls: 7.4% vs. 0.6%) (OR: 9.772, 95% CI: 3.302-28.918), gum bleeding (cases vs. controls: 27.4% vs. 11.5%) (OR: 1.732, 95% CI: 1.1-2.727), petechiae (cases vs. controls: 56.6% vs. 29.1%) (OR: 2.109, 95% CI: 1.411-3.153), and platelet count <50×109 cells/L (cases vs. controls: 53.1% vs. 25.8%) (OR: 3.419, 95% CI: 2.103-5.558) were independent predictors of GI bleeding in patients with dengue virus infection. CONCLUSIONS: Our study is the first to disclose that end stage renal disease and previous stroke, with additional comorbidities, were strongly significant associated with the risk of GI bleeding in patients with dengue virus infection. Identification of these risk factors can be incorporated into the patient assessment and management protocol of dengue virus infection to reduce its mortality.

Effects of implementation of an online comprehensive antimicrobial-stewardship program in ICUs: A longitudinal study.

BACKGROUND/PURPOSE: The long-term effects of antimicrobial-stewardship programs in the intensive care units (ICUs) have not been adequately examined. We evaluated the impact of an online comprehensive antimicrobial stewardship program (OCASP) on the outcomes of patients in 200-bed medical/surgical ICUs over the course of 11 years. METHODS: We analyzed the records of adult patients admitted to ICUs during the 5 years before (n = 27,499) and the 6 years after (n = 33,834) implementation of an OCASP. Antimicrobial consumption, expenditures, duration of treatment, incidence of healthcare-associated infections (HAIs), prevalence of HAIs caused by antimicrobial-resistant strains, and crude or sepsis-related mortality of patients were analyzed. Segmented regression analyses of interrupted time series were used to assess the significance of changes in antimicrobial use. RESULTS: Compared to the patients in the pre-OCASP period, the patients in the post-OCASP period were older, had greater disease severity, longer ICU stays, and were more likely to receive antimicrobials, but had lower antimicrobial expenditures and crude and sepsis-related mortality. The trend of overall antimicrobial use [slope of defined daily dose/1000 patient-days vs. time) increased significantly before OCASP implementation (p < 0.001), but decreased significantly after implementation (p < 0.01). The administration duration of all classes of antibiotics were significantly shorter (p < 0.001) and the incidences of HAIs were significantly lower (p < 0.001) after implementation. However, there was an increase in the proportion of HAIs caused by carbapenem-resistant Acinetobacter baumannii relative to all A. baumannii infections. CONCLUSION: Implementation of an OCASP in the ICUs reduced antimicrobial consumption and expenditures, but did not compromise healthcare quality.

Risk factors and outcomes for the acquisition of carbapenem-resistant Gram-negative bacillus bacteremia: A retrospective propensity-matched case control study.

BACKGROUND/PURPOSE: A substantial number of carbapenem-resistant Gram-negative bacilli (CR GNB) have been identified among the etiologic multidrug-resistant GNB in healthcare-associated infections. For achieving a better therapeutic outcome by minimizing inappropriate empirical antibiotic treatment before blood culture and susceptibility testing results are available, it is very important to identify patients who are at risk for the development of CR GNB bacteremia. METHODS: Retrospective analysis of propensity-score matched (PSM) adult patients with CR GNB bacteremia (PSM-group 1 [n = 95]) and those with non-CR GNB bacteremia (PSM-group 2 [n = 190]). RESULTS: PSM-group 1 was found to a significantly longer length of hospital stay (27 vs. 18 days; p < 0.001) after emerging GNB bacteremia and a higher 30-day all-cause mortality rate (27.4% vs. 5.8%; p < 0.001), when compared with PSM-2 group. Independent risk factors for the acquisition of CR GNB bacteremia were previous exposure to an antipseudomonal penicillin (odds ratio [OR] = 3.58; 95% confidence interval [CI] = 1.30-9.90), an antipseudomonal cephalosporin (OR = 3.49; 95% CI = 1.09-11.24), and a carbapenem (OR = 3.60; 95% CI = 1.37-9.47), and longer length of hospital stay before the development of GNB bacteremia (OR = 1.03; 95% CI = 1.01-1.05). CONCLUSION: Risk factors for acquisition of CR GNB bacteremia identified in this study each may serve as a reminder alerting clinicians to hospitalized patients at risk for CR GNB bacteremia requiring appropriate antibiotic coverage, and in these circumstances, combined antibiotics may be used until antimicrobial de-escalation/adjustment is clearly indicated by the subsequently identified pathogenic GNB and its susceptibility profile.

Analyses of clinical and laboratory characteristics of dengue adults at their hospital presentations based on the World Health Organization clinical-phase framework: Emphasizing risk of severe dengue in the elderly.

BACKGROUND/PURPOSE: Dengue clinically dynamically changes over time; the World Health Organization (WHO) dengue classification framework proposed 3 dengue clinical phases-febrile (days 1-3), critical (days 4-6) and recovery (days ≥7) phases. This study aimed to better understand clinical and laboratory characteristics in adults (≥18 years) suffering dengue in different clinical phases at their hospital presentations. METHODS: A retrospective analysis of adults suffering dengue between 2008 and 2014. RESULTS: Of the 669 included dengue adults, 146 (21.8%) were elderly (≥65 years), and 27 (4%) suffered severe dengue. When compared with those in febrile phase, significantly higher incidence of ascites, mucosal bleeding, and/or gastrointestinal bleeding; lower white blood cell (WBC) and platelet counts; higher hematocrit, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values were found in critical phase. When compared with their younger counterparts, elderly at febrile phase had significantly lower frequencies of bone pain, myalgia, headache and rash; higher frequencies of vomiting, pleural effusion and mucosal bleeding; higher WBC count, AST and ALT levels, and lower platelet count; in critical phase, elderly had significantly higher frequencies of pleural effusion, mucosal bleeding and gum bleeding. Four (0.6%) patients experienced severe dengue in recovery phase. Significantly higher proportions of elderly developed severe dengue in both febrile and critical phases as compared with younger adults. CONCLUSIONS: Elderly had lower frequency of classical dengue symptoms, yet were at higher risk of development of severe dengue during their early dengue course. A small number of patients developed severe dengue at the WHO-proposed recovery phase.