The clinical characteristics and therapeutic outcomes of adult patients with community-acquired spontaneous bacterial meningitis with a fulminant clinical course in Taiwan.

PURPOSE: To examine the clinical characteristics of adult patients with community-acquired spontaneous bacterial meningitis (CASBM) with a fulminant clinical course. MATERIALS AND METHODS: The clinical features and therapeutic outcomes of 127 adult CASBM patients were analyzed. The patients were divided into two groups as those with and without a fulminant clinical course. Fulminant clinical course was defined as meningitis presenting initially with marked consciousness disturbance (Glasgow Coma Scale score < 8) or a rapid deterioration in consciousness level within 48 h of hospitalization. RESULTS: Among the 127 enrolled patients, 69 had a fulminant clinical course (47 men and 22 women) and 58 did not. The patients with a fulminant clinical course had a significantly higher incidence of end-stage renal disease (ESRD), severe clinical manifestations and higher mortality rate, and the survivors had significantly worse therapeutic outcomes. Klebsiella (K.) pneumoniae (50 strains) was the most important pathogen for the development of a fulminant clinical course, and all strains were susceptible to ceftriaxone and ceftazidime. With treatment, 50.7% (35/69) of the patients with a fulminant clinical course died, and the presence of K. pneumoniae infection was significant prognostic factor. CONCLUSIONS: The presence of ESRD, initial presentation of altered consciousness, septic shock, seizures and CSF total protein level and K. pneumoniae infection were significantly associated with a fulminant clinical course of adult CASBM, and patients with this specific infectious syndrome had high mortality and morbidity rates. The presence of K. pneumoniae infection is a significant prognostic factor.

Epidemiology of Nocardia Species at a Tertiary Hospital in Southern Taiwan, 2012 to 2020: MLSA Phylogeny and Antimicrobial Susceptibility.

The identification and antimicrobial susceptibility of Nocardia spp. are essential for guiding antibiotic treatment. We investigated the species distribution and evaluated the antimicrobial susceptibility of Nocardia species collected in southern Taiwan from 2012 to 2020. A total of 77 Nocardia isolates were collected and identified to the species level using multi-locus sequence analysis (MLSA). The susceptibilities to 15 antibiotics for Nocardia isolates were determined by the broth microdilution method, and the MIC50 and MIC90 for each antibiotic against different species were analyzed. N. cyriacigeorgica was the leading isolate, accounting for 32.5% of all Nocardia isolates, and the prevalence of Nocardia isolates decreased in summer. All of the isolates were susceptible to trimethoprim/sulfamethoxazole, amikacin, and linezolid, whereas 90.9% were non-susceptible to cefepime and imipenem. The phylogenic tree by MLSA showed that the similarity between N. beijingensis and N. asiatica was as high as 99%, 73% between N. niigatensis and N. crassostreae, and 86% between N. cerradoensis and N. cyriacigeorgica. While trimethoprim/sulfamethoxazole, amikacin, and linezolid remained fully active against all of the Nocardia isolates tested, 90.9% of the isolates were non-susceptible to cefepime and imipenem.

Oral Bacteria and Their Antibiotic Susceptibilities in Taiwanese Venomous Snakes.

Wound infections after venomous snakebites are clinically important. Information regarding the nature and antibiotic susceptibilities of snake oral bacterial flora could support empiric antibiotic therapy. Wild venomous snakes were collected from southern Taiwan: a total of 30 each of Bungarus multicinctus, Naja atra, Protobothrops mucrosquamatus, and Trimeresurus stejnegeri; 3 Deinagkistrodon acutus; and 4 Daboia siamensis. The species and antibiotic susceptibilities of their oral bacteria were determined. Aerobic gram-negative bacteria, especially Pseudomonas aeruginosa and Proteus vulgaris, were the most abundant. Proteus vulgaris were more abundant in B. multicinctus, N. atra, and P. mucrosquamatus than in T. stejnegeri (40%, 43.3%, and 40% vs. 13.3%, respectively). The gram-negative species were less susceptible to first- and second-generation cephalosporins and ampicillin-sulbactam than to third-generation cephalosporins, fluoroquinolones, carbapenems, or piperacillin-tazobactam. The most abundant aerobic gram-positive species cultured was Enterococcus faecalis, which was more abundant in N. atra than in other snakes (p < 0.001) and was highly susceptible to ampicillin, high-level gentamicin, penicillin, teicoplanin, and vancomycin. Bacteroides fragilis and Clostridium species were the most common anaerobic bacteria. The anaerobic organisms were highly susceptible to metronidazole and piperacillin. As a reference for empiric antimicrobial therapy, third-generation cephalosporins, fluoroquinolones, carbapenems, or piperacillin-tazobactam can be initiated in venomous snakebites wound infections.

Incidence rates, emerging serotypes and genotypes, and antimicrobial susceptibility of pneumococcal disease in Taiwan: A multi-center clinical microbiological study after PCV13 implementation.

Objectives The multi-center clinical microbiological study in Taiwan aimed to evaluate the impact of childhood PCV13 immunization on pneumococcal disease, and the magnitude of serotype replacement in invasive and non-invasive pneumococcal disease among all age groups. Methods The study of culture-confirmed pneumococcal disease (CCPD) was conducted at four hospitals across Taiwan in 2015-2018. Pneumococcal pneumonia was defined as clinical diagnosis with positive sputum or bronchoalveolar lavage culture. Serotyping, multi-locus sequence typing, and antimicrobial susceptibility testing for penicillin and ceftriaxone were performed. Results A total of 1413 CCPD cases were identified. Invasive pneumococcal disease (IPD) accounted for 13.4% (190/1413) of CCPD. PCV7-type CCPD incidence declined among all age groups between 2015 and 2018. In adults aged 50-64 years, PCV7-type pneumococcal pneumonia incidence in 2018 was 72% lower than that in 2015, and all pneumococcal pneumonia incidence was 35% lower than that in 2015. In children, CCPD incidence was higher in 2018 than in 2015 (IRR 1.75 for age < 5 years, IRR 1.56 for age 5-17 years). Incidence of CCPD caused by non-PCV13-types, mainly 15A and 23A, increased significantly in those younger than 50 years. Serotypes 19A and 19F constituted the largest clonal complex, CC236/320 (n = 280, 19.8%). The rates of penicillin and ceftriaxone non-susceptibility were higher in PCV13-type isolates. Conclusions Childhood PCV13 immunization exerted an indirect protection to vaccine serotype clinically defined non-bacteremic pneumococcal pneumonia among adults, especially those between 50 and 64 years of age. Emerging non-PCV13 serotypes mainly caused non-invasive mucosal disease among children.

The emergence of Clostridioides difficile PCR ribotype 127 at a hospital in northeastern Taiwan.

BACKGROUND: Several studies have highlighted the incidence of Clostridioides difficile infections (CDIs) in Taiwan and certain ribotypes have been related to severe clinical diseases. A study was conducted to investigate the polymerase chain reaction (PCR) ribotypes and genetic relatedness of clinical C. difficile strains collected from January 2009 to December 2015 at a hospital in northeastern Taiwan. MATERIAL AND METHODS: A modified two-step typing algorithm for C. difficile was used by combining a modified 8-plex and 3'-truncated tcdA screening PCR. In addition, MLVA typing was adopted for investigation of bacterial clonality and transmission. RESULTS: Among a total of 86 strains, 24 (28%) were nontoxigenic and 62 (72%) had both tcdA and tcdB (A + B+). No tcdA-negative and tcdB-positive (A-B+) strains were identified. Binary toxin (CDT)-producing (cdtA+/cdtB+) strains were started to be identified in 2013. The 21 (34%) A+B+ clinical strains with binary toxin and tcdC deletion were identified as RT127 strains, which contained both RT078-lineage markers and fluoroquinolone (FQ)-resistant mutations (Thr82Ile in gyrA). Multiple loci variable-number tandem repeat analysis (MLVA) for phylogenetic relatedness of RT127 strains indicated that 20 of 21 strains belonged to a clonal complex that was identical to a clinical strain collected from southern Taiwan in 2011, suggestive of a clonal expansion in Taiwan. CONCLUSION: A two-step typing method could rapidly confirm species identification and define the toxin gene profile of C. difficile isolates. The clonal expansion of RT127 strains in Taiwan indicates monitoring and surveillance of toxigenic C. difficile isolates from human, animal, and environment are critical to develop One Health prevention strategies.

The Clinical Characteristics and Therapeutic Outcomes of Escherichia Coli Meningitis in Adults.

BACKGROUND: To examine the clinical characteristics and therapeutic outcome of Escherichia (E.) coli adult bacterial meningitis (ABM). METHODS: The demographic data, clinical and laboratory features and therapeutic outcome of 25 E. coli ABM patients were examined retrospectively. The clinical features of the reported E. coli ABM cases were also included for analysis. RESULTS: The 25 E. coli ABM patients included 12 women and 13 men, aged 33-78 years (mean= 59.9). Of these 25 patients, 13 had a postneurosurgical state as the underlying condition. As to the underlying medical conditions, diabetes mellitus was the most common, found in 9 of the 25 cases. Of the clinical manifestation, severe neurologic manifestations including altered consciousness (19), hydrocephalus (10), seizure (7) acute/subacute cerebral infarct (5), brain abscess (2), subdural empyema (1) and spinal abscess (1) were found, and the other clinical features included fever (21), septic shock (8), bacteremia (6) and hyponatremia (3). With treatment, the mortality rate was more than 44.0% and the presence of septic shock was a significant prognostic factor. With literature review, 29 community-acquired and 12 postneurosurgical E. coli ABM cases were enrolled, and severe neurologic manifestation and high mortality rate were also found. CONCLUSIONS: This preliminary overview of E. coli ABM revealed the underlying conditions, severe neurologic manifestation and high mortality rate. Further large-scale, prospective study is needed for a better delineation of this specific infectious syndrome of adult E. coli meningitis.

Rapid antimicrobial susceptibility tests on an integrated microfluidic device for precision medicine of antibiotics.

This study reports an integrated microfluidic device that was capable of executing rapid antimicrobial susceptibility tests with one, two, or even three antibiotics against two clinically isolated multi-drug-resistant bacteria strains (including carbapenem-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus). Bacteria were automatically mixed for 10 min with serially diluted antibiotics with a novel, membrane-type micromixer consisting of two circular micropumps, and the minimum inhibitory concentrations (MIC) were then determined via simple colorimetric reactions in only 4.5-6 h using only 3 µL of bacteria sample of each reaction (as opposed to 24 h and 50 µL, respectively, with the conventional broth micro-dilution method). In addition to determining MICs of antibiotics (ceftazidime, gentamicin, meropenem, vancomycin and linezolid), interaction effects across antibiotics combinations (gentamicin/meropenem or ceftazidime/gentamicin/meropenem) at different dosages were explored. The efficacy of polypharmacy showed additivity when gentamicin or ceftazidime/gentamicin were combined with meropenem to treat carbapenem-resistant Escherichia coli. This represents the first time that the perplexing clinical decision to choose multiple antibiotics for combination therapy against drug resistant bacteria can be realized on an integrated microfluidic device within 6 h.

An integrated microfluidic system for early detection of sepsis-inducing bacteria.

Since early diagnosis of sepsis may assist clinicians in initiating timely, effective, and prognosis-improving antibiotic therapy, we developed an integrated microfluidic chip (IMC) for rapid isolation of both Gram-positive and Gram-negative bacteria from blood. The device comprised a membrane-based filtration module (90 min operating time), a bacteria-capturing module using a micro-mixer containing magnetic beads coated with "flexible neck" regions of mannose-binding lectin proteins for bacteria capture (20 min), and a miniature polymerase chain reaction (PCR) module for bacteria identification (90 min via TaqMan® probe technology). The filter separated all white blood cells and 99.5% of red blood cells from bacteria, which were captured at rates approaching 85%. The PCR assay's limit of detection was 5 colony-forming units (CFU) per reaction, and the entire process was completed in only 4 h. Since this is far less than that for culture-based approaches, this IMC may serve as a promising device for detection of sepsis.

A Genomic Approach to Investigating Ocular Surface Microorganisms: Monitoring Core Microbiota on Eyelid Margin with a Dot hybridization Assay.

A sound ocular surface microbiota has been recognized as a part of ocular surface health following a growing body of evidence from next-generation sequencing technique and metagenomic analysis. However, even from the perspective of contemporary precision medicine, it is difficult to directly apply these new technologies to clinical practice. Therefore, we proposed a model based on dot hybridization assay (DHA) to bridge conventional culture with a metagenomic approach in investigating and monitoring ocular surface microbiota. Endophthalmitis, mostly caused by bacterial infection, is the most severe complication of many intraocular surgeries, such as cataract surgery. Hazardous microorganisms hiding and proliferating in the ocular surface microbiota not only increase the risk of endophthalmitis but also jeopardize the effectiveness of the preoperative aseptic procedure and postoperative topical antibiotics. The DHA model enables the simultaneous assessment of bacterial bioburden, detection of target pathogens and microorganisms, and surveillance of methicillin/oxacillin resistance gene mecA in the ocular surface microbiota. This assay revealed heavier bacterial bioburden in men, compatible with a higher risk of endophthalmitis in male patients who underwent cataract surgery. No occurrence of endophthalmitis for these patients was compatible with non-hazardous microorganisms identified by specific dots for target pathogens. Moreover, the mecA dot detected oxacillin-resistant strains, of which culture failed to isolate. Therefore, the DHA model could provide an alternative genomic approach to investigate and monitor ocular surface microorganisms in clinical practice nowadays.

Rapid diagnosis of periprosthetic joint infection from synovial fluid in blood culture bottles by direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

BACKGROUND: The aim of this prospective study was to use direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to rapidly diagnose periprosthetic joint infections (PJIs). METHOD: Synovial fluid was taken from 77 patients (80 joints, 41 hips and 39 knees) who met the International Consensus Meeting criteria for PJI, and inoculated into blood culture bottles (BCBs) and onto conventional swabs. Positive blood cultures were analyzed using either direct or routine MALDI-TOF MS. Pathogen identification and the time to identification was recorded. Differences between groups were analyzed using the Kruskal-Wallis test and Bonferroni's post-hoc test. RESULTS: Direct and routine MALDI-TOF MS both detected 64 positive results (80%), compared to 47 (59%) by conventional swabs (p = 0.002). Direct MALDI-TOF MS identified 85.3% of the gram-positive organisms and 92.3% of the gram-negative organisms. No fungi were identified by direct MALDI-TOF MS. In 17 BCBs that were flagged positive, identification by direct MALDI-TOF MS failed. Among the positive results in the direct MALDI-TOF MS group, Staphylococcus aureus accounted for 47%, followed by Staphylococcus epidermidis (17%), Escherichia coli (9%) and Klebsiella pneumoniae (9%). The median time to microorganism identification was significantly shorter with direct MALDI-TOF MS (12.7 h, IQR: 8.9-19.6 h) than with routine MALDI-TOF MS (39.5 h, IQR: 22.8-46.0 h) or swabs (44.4 h, IQR: 27.2-72.6 h) (p < 0.0001). In pairwise comparisons, there were significant differences in the time of microorganism identification between direct MALDI-TOF MS and routine MALDI-TOF MS (p < 0.0001) or swab culture (p < 0.0001). There was no significant difference between routine MALDI-TOF MS and swab culture (p = 0.0268). CONCLUSION: Compared with current laboratory practice, direct MALDI-TOF MS shortened the time to microorganism identification and had superior results compared to conventional swabs, except for fungi. Further studies should investigate whether the earlier administration of appropriate antimicrobial agents can improve the treatment outcomes of PJIs.

Impact of biofilm production by Candida species and antifungal therapy on mortality of patients with candidemia.

BACKGROUND AND OBJECTIVES: Few studies have investigated the clinical outcomes of patients with candidemia caused by Candida species with different levels of biofilm formation. We aimed to investigate the impact of antifungal therapy on the outcome of candidemia caused by Candida species that were categorised as low biofilm formers (LBFs), moderate biofilm formers (MBFs), and high biofilm formers (HBFs). METHODS: Adults with candidemia caused by LBF and HBF/MBF Candida species that were susceptible to fluconazole and caspofungin were included to investigate the impact of treatment with fluconazole vs an echinocandin on 30-day crude mortality. RESULTS: In total, 215 patients with candidemia received fluconazole and 116 patients received an echinocandin. In multivariate analysis, Pittsburgh bacteremia score ≥ 4 (adjusted odds ratio [AOR] =2.42; 95% confidence interval [CI], 1.32-4.41), malignancy (AOR = 3.45; 95% CI, 1.83-6.51), not removing the central venous catheter within 48 hours of a positive blood culture (AOR = 4.69; 95% CI, 2.61-8.45), and treatment with fluconazole for candidemia due to HBF/MBF Candida spp. (AOR = 2.23; 95% CI, 1.22-4.06) were independent factors associated with 30-day mortality. Of the 165 patients infected by HBF/MBF Candida isolates, those who received azole therapy had a significantly higher sepsis-related mortality rate than those who received echinocandin therapy (44.9% [49/109] vs 26.8% [15/56], P = .03). CONCLUSIONS: There was a trend of an independent association between fluconazole treatment and poor outcomes in the patients infected by HBF/MBF Candida strains.

High incidence of severe neurological manifestations and high mortality rate for adult Listeria monocytogenes meningitis in Taiwan.

The clinical characteristics and therapeutic outcomes of adult Listeria monocytogenes meningitis are not commonly examined in isolation in the literature. During a study period of 19 years (2000-2018), 366 patients with culture-proven adult bacterial meningitis (ABM) were identified in the author's hospital (264 patients in 2000-2010 and 102 patients in 2011-2018). Of the 366 ABM patients, 330 had monomicrobial infections while the other 36 had mixed infections. L. monocytogenes infection was identified in 11 of the 330 patients with monomicrobial ABM (3 in 2000-2010 and 8 in 2011-2018). These 11 patients included 5 males and 6 females, aged 47 to 76 years (median age = 61.7). None of the 11 patients had a postneurosurgical state as the underlying cause, but 3 of them contracted the infection nosocomially. Common underlying conditions included liver cirrhosis (4), systemic malignancy (3), diabetes mellitus (3), and renal disease (2). The most common clinical manifestations were fever (11), altered consciousness (8), seizure (8), bacteremia (7) and hydrocephalus (5). The therapeutic result revealed a mortality rate of 72.7% (8/11), but no significant prognostic factors were identified. The clinical features of 8 additional Taiwanese L. monocytogenes ABM patients reported in the literature, were also included for analysis. The present study revealed an increase in L. monocytogenes ABM in recent years and most patients presented with severe neurological manifestations. The current study is a preliminary overview of L. monocytogenes meningitis in adults and a further large-scale study is needed for improved delineation of this specific infectious syndrome.

An integrated microfluidic system for antimicrobial susceptibility testing with antibiotic combination.

Polypharmacy is routinely administered to fight severe infections, though it has led to rampant multi-drug resistance in many bacterial strains. Preferably, antimicrobial susceptibility testing (AST) would be carried out prior to antibiotic prescription, though it is generally thought to be too complex and labor-intensive. In order to assist clinicians with better antibiotic administration for the effective treatment of bacterial infections, an integrated microfluidic system (IMS) capable of automating AST for 1-2 antibiotics against clinical bacterial pathogens was developed herein. Accurate determination of the minimum and fractional inhibitory concentrations of vancomycin, gentamicin, and linezolid were determined by assaying growth of two clinical methicillin-resistant Staphylococcus aureus isolates via a colorimetric assay on-chip. By applying various antibiotic combinations against a single pathogen in multiple chambers, the IMS could identify the optimal drug combination and the minimum effective dosage by evaluating the fractional inhibitory concentration index. This IMS possessed several advantages over conventional methods, including (1) a 50% reduction in bacterial sample and reagent volume (<50 µL per well), (2) less potential for human error due to its automatic nature, (3) faster liquid manipulation time by integrating the microfluidic components rather than labor-intensive process, and (4) straightforward result interpretation via colorimetric change instead of turbidity degree. Personalized medicine for treatment of bacterial infections may therefore be realized using this IMS.

Tracking the Reflective Light Particles Spreading on the Cornea: An Emerging Assessment for Tear Film Homeostasis.

PURPOSE: To implement an emerging noninvasive approach for assessing the dynamic tear film (TF) homeostasis. METHODS: The video records of dynamic TF from 12 healthy orthokeratology lens wearers were obtained by a clinically available TF analyzer and decomposed as image sequences. The trajectories of TF particles were analyzed by two tracking models, the full-span model (FSM) and the fixed-duration model (FDM). FSM tracked a particle for a complete opening blink cycle, while FDM tracked 1 second of the same cycle. A power-law fitting operation [Formula: see text] was used to extract homeostasis markers based on the tracking model for each subject. RESULTS: Comparing two tracking models (N = 6), only one subject had statistical difference in averaged momentary moving speed (MMS; P = 0.0488), while none had significant difference in averaged momentary moving direction (MMD). However, both models showed good correlations in average MMS (ρ = 0.94, P = 0.0048) and MMD (ρ = 1.00, P < 0.0001) and all extracted homeostasis markers [α, ß, MMS(0.1), and MMS(2.0)]. Assessing interblink reliability in these markers under FDM tracking (N = 12), only one subject in the MMS (0.1) and another subject in the MMS (2.0) were outside 95% limits of agreement, respectively. CONCLUSIONS: FDM is a good alternative to FSM and has tracking properties of higher efficiency and easier implementation. The homeostasis markers under FDM tracking showed a good interblink consistence; therefore this approach will be a promising method for analyzing dynamic TF homeostasis in future practice. TRANSLATIONAL RELEVANCE: FDM analytical architecture can practice the past experimental platform on a TF analyzer to obtain homeostasis markers of TF.

The clinical characteristics of spontaneous Gram-negative bacterial meningitis in adults: A hospital-based study.

The epidemiologic trend of acute bacterial meningitis can change more dramatically than any other bacterial disease, and a decrease in spontaneous adult bacterial meningitis (ABM) has been noted in serial studies of the epidemiologic trend of ABM in Taiwan. The purpose of this study was to analyze the clinical characteristics, laboratory data and therapeutic outcomes of 149 patients with spontaneous Gram-negative (G(-)) ABM collected during a study period of 31 years (1986-2016). The 149 patients included 107 men and 42 women, aged 18-86 years. The common underlying conditions were diabetes mellitus, liver cirrhosis and alcoholism, and the leading clinical presentations were fever, altered consciousness and septic shock. Compared the clinical characteristics of the patients identified in the study period of 2001-2106 to the patients identified in the study period of 1986-2000, the former group of patients had a significantly higher incidence of systemic malignance. In the recent 16 years (2001-2016), Klebsiella pneumoniae, Pseudomonas spp. and Escherichia coli were the leading three implicated bacterial pathogens of spontaneous G(-) ABM, accounting for 61.3% (38/62), 11.3% (7/62) and 11.3% (7/62%) of all cases, respectively. The overall mortality rate from spontaneous G(-) ABM was high (47.0%, 70/149) and the presence of septic shock and lower cerebrospinal fluid glucose level were significant prognostic factors. Because of the decreasing incidence of spontaneous ABM in Taiwan, close examination of this specific infectious syndrome is important in order to monitor the epidemiologic trend and improve the therapeutic strategy.

Relation between flomoxef minimum inhibitory concentrations and clinical outcomes of patients treated with flomoxef for Enterobacteriaceae bacteremia.

BACKGROUND: Flomoxef is potentially effective against ß-lactamase-producing Enterobacteriaceae because limited clinical data demonstrate its effectiveness against Enterobacteriaceae bloodstream infections (BSIs) based on its minimum inhibitory concentrations (MICs). This study was conducted to determine the optimal breakpoints based on the survival of patients with Enterobacteriaceae BSIs treated with flomoxef. METHODS: The 30-day crude mortality rate was analyzed among 224 adults who initiated flomoxef monotherapy for Enterobacteriaceae BSIs at a medical center over a 3-year period, according to the flomoxef MICs of the initial isolates. The outcome was evaluated by classification and regression tree modeling and by logistic regression analysis. RESULTS: The 30-day crude mortality was approximately two fold greater in patients whose isolates had flomoxef MICs of ≥2 mg/L (54.9% [62/113]) than in those with isolates with MICs of ≤1 mg/L (26.1% [29/111]); the differences were significant in bivariate analysis (P<0.01) and in survival analysis (log-rank test; P<0.001). The classification and regression tree analysis revealed a split between MICs of 1 and 2 mg/L and predicted the same difference in mortality, with a P-value of <0.001. Flomoxef for Enterobacteriaceae BSIs caused by isolates with flomoxef MICs of ≥2 mg/L was an independent predictor of 30-day crude mortality (adjusted OR 3.76, 95% CI 1.94-7.29). CONCLUSION: Patients with Enterobacteriaceae bacteremia who received flomoxef had a lower 30-day crude mortality when the flomoxef MICs of the isolates were ≤1 mg/L than those with MICs ≥2 mg/L.

Impact of teicoplanin maintenance dose and MIC values on the clinical outcomes of patients treated for methicillin-resistant Staphylococcus aureus bacteremia.

OBJECTIVES: Teicoplanin, a glycopeptide, is regarded as among the drug choices for methicillin-resistant Staphylococcus aureus (MRSA) infections. Few studies have evaluated the relationship between teicoplanin minimal inhibitory concentrations (MICs) and outcomes among patients with serious MRSA infections. SUBJECTS AND METHODS: We investigated the relationship between teicoplanin maintenance dose and clinical outcomes, on the completion of teicoplanin therapy, in bacteremia patients with MRSA infection, with different teicoplanin MICs. A total of 146 adult patients with MRSA bacteremia were enrolled at Kaohsiung Chang Gung Memorial Hospital between September 2012 and September 2015. RESULTS: A higher number of patients in the high-dose regimen group (6 mg/kg/12 h) had favorable outcomes than those in the standard-dose regimen group (6 mg/kg/24 h) (84.1% vs 41.2%; p<0.01), regardless of the teicoplanin MICs. In the multivariate analysis, a Pittsburgh bacteremia score ≥4 (OR, 0.07, 95% CI, 0.03-0.19) was a risk factor for an unfavorable final clinical response, whereas high-dose teicoplanin maintenance therapy for MRSA bacteremia was significantly associated with a favorable final response (OR, 25.3 [95% CI, 4.43-144.03] for isolates with a teicoplanin MIC ≥1.5 mg/L and OR, 5.6 [95% CI, 1.57-19.91] for isolates with a teicoplanin MIC <1.5 mg/L). Survival at 30 days was significantly better for patients receiving high-dose teicoplanin maintenance treatment, regardless of the teicoplanin MICs of the MRSA isolates. Patients were selected using propensity score matching, based on the independent predictors of a favorable final outcome. After appropriate propensity score matching, patients in the high-dose regimen group still had a statistically significant favorable outcome at the end of treatment (84.1% vs 40.9%; p<0.01). CONCLUSION: The results suggested that high-dose teicoplanin maintenance treatment is associated with more favorable outcomes than standard-dose teicoplanin maintenance treatment, for patients with MRSA bacteremia, regardless of the teicoplanin MIC.

Clinical characteristics of Citrobacter meningitis in adults: High incidence in patients with a postneurosurgical state and strains not susceptible to third-generation cephalosporins.

Adult bacterial meningitis (ABM) caused by Citrobacter (C.) infection is very uncommon and the clinical characteristics of this specific infectious syndrome have not been analyzed in the literature. The clinical characteristics of six Citrobacter ABM patients collected during a study period of 30 years (1986-2015) were enrolled, and they accounted for 1.1% (6/540) of our ABM patients. In this study, a total of 14 patients with Citrobacter ABM (six collected from our hospital and eight from the literature) were included for analysis. The 14 patients were nine men, three women and two with unknown gender, aged 31-84 years (median: 64 years), of whom 78.6% (11/14) had an underlying postneurosurgical condition and 21.4% (3/14) belonged to mixed infections. The most common clinical manifestations were fever (50%, 7/14), altered consciousness (50%, 7/14), and headache (28.6%, 4/14). These clinical presentations were neither specific nor unique; therefore, cerebrospinal fluid studies including cultures were important for the diagnostic confirmation. Of the implicated Citrobacter strains, C, koseri was the most common (57.1%, 8/14), followed by C. freundii (21.4%, 3/14) and C. farmeri (7.1%, 1/14). Of the Citrobacter strains collected from CSF specimens of our six Citrobacter ABM patients, 33.3% (2/6) and 66.7% (4/6) were not susceptible to ceftazidime or ceftriaxone, respectively, but they were all susceptible to carbapenem. The therapeutic results showed a mortality rate of 21.4% (3/14).