OBJECTIVES:Aztreonam-avibactam (ATM-AVI) and cefiderocol (CFDC) are two next-generation antibiotics that exhibit promising in vitro activity against metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE). However, differences in antibacterial spectra and resistance mechanisms among clinically important Gram-negative bacteria (GNB) between these two agents remain incompletely understood. METHODS:English-language publications indexed in PubMed (1990-2026), records retrieved from Google Scholar, and the 2018-2024 Antimicrobial Testing Leadership and Surveillance database were extensively reviewed to assess their potential clinical utility. RESULTS:ATM-AVI demonstrates broad activity against KPC-, MBL- and OXA-48/181-like-producing CRE. However, ATM-AVI non-susceptibility occurs in Escherichia coli and Providencia rettgeri isolates harboring blaCMY, penicillin-binding protein 3 (PBP3) modifications, and porin dysfunction or acrA efflux overexpression. In contrast, CFDC activity is primarily compromised by NDM production, reduced expression of iron transporters, and PBP3 alterations. Significant regional variation in CFDC susceptibility among MBL-producing CRE isolates collected in Asia and North America/Europe has been observed. Based on limited pooled real-world treatment experience, CFDC shows moderate efficacy (73%) for the treatment of infections caused by MBL-producing CRE. Both antibiotics also show potential in vitro activity against ceftazidime-avibactam-resistant, non-carbapenemase-producing CRE. Notably, CFDC exhibits excellent in vitro activity against contemporary CR-Pseudomonas aeruginosa, most CR-Acinetobacter baumannii harboring blaOXA-23/24/58 genes, Elizabethkingia anophelis, Stenotrophomonas maltophilia, Burkholderia cepacia and Burkholderia pseudomallei. Nevertheless, CFDC heteroresistance is most prevalent among CR-A. baumannii isolates. CONCLUSIONS:Continued assessment of clinical treatment experience with these two antibiotics against MBL-producing CRE and important non-fermenting GNB is warranted to accumulate further evidence regarding their therapeutic roles.

OBJECTIVES:A total of 2361 ceftazidime-avibactam-resistant non-carbapenemase-producing (CP) carbapenem-resistant Enterobacterales (CRE) isolates were identified, accounting for 45.8% of global non-CP-CRE (n = 5156) and 3.0% of all Enterobacterales isolates (n = 78 371) during 2020-23. The high prevalence of non-CP-CRE resistant to ceftazidime-avibactam prompted investigations into alternative antibiotics for the effective management of ceftazidime-avibactam-resistant non-CP-CRE infections. METHODS:Using the susceptibility breakpoints for Enterobacterales recommended by CLSI 2025 (for ceftazidime-avibactam, amikacin and meropenem-vaborbactam), EUCAST 2025 (for aztreonam-avibactam, colistin) and the US FDA (for tigecycline), susceptibility data of key antibiotics against global ceftazidime-avibactam-resistant non-CP-CRE isolates were extracted from the 2020-23 Antimicrobial Testing Leadership and Surveillance database. Additionally, data on genes encoding ESBL and plasmid-mediated AmpC enzymes were also analysed. RESULTS:In vitro susceptibility rates of global ceftazidime-avibactam-resistant non-CP-CRE isolates to aztreonam-avibactam, colistin and tigecycline all exceeded 86%. In contrast, non-susceptibility rates to amikacin and meropenem-vaborbactam were 78.7% and 94.8%, respectively. These high non-susceptibility rates for amikacin and meropenem-vaborbactam persisted regardless of region, infection source or species [Klebsiella pneumoniae (n = 1576), Escherichia coli (n = 388) and potentially chromosomal AmpC hyperproducers (n = 337)]. The prevalence of blaCTX-M-15 (the predominant ESBL) was closely correlated with amikacin non-susceptibilities across all three species groups (r = 0.901; P = 0.286). CONCLUSION:Based on the data from this study, poor in vitro susceptibility rates for amikacin and meropenem-vaborbactam against contemporary ceftazidime-avibactam-resistant non-CP-CRE were observed. In contrast, aztreonam-avibactam, colistin and tigecycline appear to be reasonable options for the management of infections caused by ceftazidime-avibactam-resistant non-CP-CRE.

Objective:The 2024 global cryptococcosis treatment guidelines suggests that fluconazole (FLC) combined with liposomal amphotericin B (AMB) and 5-flucytosine (5-FC) as the mainstay of treatment for systemic cryptococcosis. Although this 2024 guidelines also list recommend voriconazole (VRC), posaconazole (POS), and isavuconazole (ISA) as alternatives to FLC during the consolidation and maintenance phases, current data on distributions of minimum inhibitory concentrations (MICs) of global Cryptococcus isolates for antifungals-and studies evaluating the application of their pharmacokinetic (PK) profiles and pharmacodynamic (PD) indices in the treatment of systemic cryptococcosis-remain limited. To optimize antifungal dosing, integration of global MIC distributions for Cryptococcus isolates with PK/PD parameters for key antifungal agents is needed. Methods:This study analyzed the MIC distributions from the 2010-2023 antifungal Antimicrobial Testing Leadership and Surveillance database, and determined epidemiological cutoff values for major Cryptococcus species. Results:The majority of invasive Cryptococcus isolates were classified as wild-type strains (>90%). We analyzed PK profiles (particularly central nervous system [CNS] penetration from the bloodstream), PD indices of antifungals (azoles and AMB) against yeasts. Based on 25 studies clearly describing PK-PD relationships, FLC and VRC were considered optimal choices because of superior CNS penetration. The optimal dose of FLC is 800-1,200 mg/day, whereas dosages of VRC and ISA do not require adjustment. Nevertheless, therapeutic drug monitoring for VRC is warranted during its prescription due to significant variability in plasma concentrations influenced by multiple factors. POS is not suitable for induction therapy in systemic cryptococcosis. Additionally, ISA is preferred over POS for consolidation therapy for Cryptococcus meningitis/meningoencephalitis (MME) based on differences in their PK profiles. Furthermore, a single 10 mg/kg dose of liposomal AMB-a cost-effective strategy-should be combined with 1,200 mg/day FLC and 5-FC, or alternatively VRC, as an effective induction-phase regimen for treating Cryptococcus MME. Conclusion:Diverging from the 2024 guidelines, this study provides novel insights into the treatment of Cryptococcus MME based on MIC distributions and PK-PD indices for antifungal agents.

BACKGROUND:Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), or long COVID, encompasses persistent symptoms following acute COVID-19, impacting quality of life. This study delineates the epidemiology, clinical presentation, and quality of life effects of long COVID in Northern Taiwan using data from the 2021 COVID-19 home quarantine telemedicine care system. METHODS:A prospective cohort of 625 PCR-confirmed COVID-19 patients, diagnosed between April and October 2021, was monitored for 3-6 months post-recovery. We assessed persistent symptoms, quality of life via the EQ-5D questionnaire, and risk factors including age, sex, vaccination status, household clusters, and hospitalization. RESULTS:Among participants, 22 % reported malaise, 14 % dyspnea, and 7 % cough as persistent symptoms. Older age (≥65 years) and hospitalization were associated with greater quality of life impairment across EQ-5D domains (OR = 2.72, 95 % CI: 1.60-4.63, p < 0.001). Vaccinated individuals (7 %) showed a non-significant trend toward better EQ-5D scores (p = 0.116, 95 % CI: 0.05 to 0.20). CONCLUSIONS:Older age and hospitalization significantly predict long-term quality of life impairment in long COVID. Targeted interventions for these groups and robust post-recovery support are essential. Limitations include reliance on self-reported data, a low vaccination rate (7 %), a 3-6 months follow-up, and a single-center design, which may limit generalizability. Multi-center studies with longer follow-ups and objective biomarkers are needed to enhance further understanding.

INTRODUCTION:Acinetobacter baumannii complex (Abc) is currently a significant cause of difficult-to-treat pneumonia. Due to the high prevalence rates of carbapenem- and extensively drug-resistant (CR, XDR) phenotypes, limited antibiotic options are available for the effective treatment of pneumonia caused by CR/XDR-Abc. AREAS COVERED:In vitro susceptibility data, relevant pharmacokinetic profiles (especially the penetration ratios from plasma into epithelial-lining fluid), and pharmacodynamic indices of key antibiotics against CR/XDR-Abc are reviewed. EXPERT OPINION:Doubling the routine intravenous maintenance dosages of conventional tigecycline (100 mg every 12 h) and minocycline (200 mg every 12 h) might be recommended for the effective treatment of pneumonia caused by CR/XDR-Abc. Nebulized polymyxin E, novel parenteral rifabutin BV100, and new polymyxin derivatives (SPR206, MRX-8, and QPX9003) could be considered supplementary combination options with other antibiotic classes. Regarding other novel antibiotics, the potency of sulbactam-durlobactam (1 g/1 g infused over 3 h every 6 h intravenously) combined with imipenem-cilastatin, and the β-lactamase inhibitor xeruborbactam, is promising. Continuous infusion of full-dose cefiderocol is likely an effective treatment regimen for CR/XDR-Abc pneumonia. Zosurabalpin exhibits potent anti-CR/XDR-Abc activity in vitro, but its practical use in clinical therapy remains to be evaluated. The clinical application of antimicrobial peptides and bacteriophages requires validation.

BackgroundThis study aimed to characterize carbapenem-nonsusceptible Acinetobacter (CNSA) isolated from patients with bacteremia from 1997 to 2015.MethodsA total of 173 CNSA (12.3%) was recovered from 1403 Acinetobacter isolates. The presence of selected β-lactamase genes in CNSA was determined by PCR amplification. The conjugation test was used to determine the transferability of metallo-β-lactamase (MBL)-carrying plasmids. Whole genome sequencing in combination with phenotypic assays was carried out to characterize MBL-plasmids.ResultsIn general, a trend of increasing numbers of CNSA was observed. Among the 173 CNSA, A. baumannii (54.9%) was the most common species, followed by A. nosocomialis (23.1%) and A. soli (12.1%). A total of 49 (28.3%) CNSA were extensively drug-resistant, and all were A. baumannii. The most common class D carbapenemase gene in 173 CNSA was blaOXA-24-like (32.4%), followed by ISAba1-blaOXA-51-like (20.8%), ISAba1-blaOXA-23 (20.2%), and IS1006/IS1008-blaOXA-58 (11.6%). MBL genes, blaVIM-11, blaIMP-1, and blaIMP-19 were detected in 9 (5.2%), 20 (11.6%), and 1 (0.6%) CNSA isolates, respectively. Transfer of MBL genes to AB218 and AN254 recipient cells was successful for 7 and 6 of the 30 MBL-plasmids, respectively. The seven AB218-derived transconjugants carrying MBL-plasmids produced less biofilm but showed higher virulence to larvae than recipient AB218.ConclusionsOur 19-year longitudinal study revealed a stable increase in CNSA during 2005–2015. blaOXA-24-like, ISAba1-blaOXA-51-like, and ISAba1-blaOXA-23 were the major determinants of Acinetobacter carbapenem resistance. MBL-carrying plasmids contribute not only to the carbapenem resistance but also to A. baumannii virulence.

OBJECTIVES:Individuals infected with extensively-drug-resistant (XDR) Acinetobacter baumannii are difficult to cure and have a high mortality rate. This study compared the genomic and phenotypic differences between XDR and non-multi-drug-resistant (MDR) A. baumannii, and further characterized hypervirulent XDR A. baumannii. METHODS:In total, 1403 acinetobacter isolates were collected from patients with bacteraemia between 1997 and 2015. Antimicrobial susceptibility tests were performed to categorize isolates into non-MDR, MDR and XDR groups. The presence of selected virulence-associated genes was determined by polymerase chain reaction. Bacterial phenotypes, including iron acquisition, biofilm formation, capsule production, and virulence to larvae and mice, were determined. RESULTS:Multi-locus sequence typing revealed a high prevalence of sequence type (ST) 2 (81.6%) and ST129 (18.4%) among 49 XDR isolates, and the STs of 18 non-MDR isolates were more diverse. Virulence-associated phenotypic assays showed that XDR isolates had higher iron acquisition ability, greater capsule production, and virulence to Galleria mellonella larvae. However, their ability to form biofilm was lower compared with that of non-MDR isolates. XDR isolates were more likely to have virulence genes (tonB, hemO, abaI and ptk), while non-MDR isolates were more likely to have pld and ompA genes. Twenty-one XDR isolates that had a <20% larvae survival rate after 7 days post-infection were defined as hypervirulent XDR isolates. Among them, isolates 1677 (ST129) and 929-1 (ST2) caused the death of all infected mice within 2 days. CONCLUSION:Some subpopulations of highly-drug-resistant ST2 isolates exhibit high virulence. As such, it is of utmost importance to continue monitoring the spread of hypervirulent XDR A. baumannii isolates.

This study examined the geographic distribution of minimum inhibitory concentrations (MICs) of antifungals against Cryptococcus isolates. Data were collected on the MICs of specific antifungals (amphotericin B, 5-flucytosine, fluconazole, voriconazole, posaconazole, and isavuconazole) against various Cryptococcus species for the period 2010 to 2020 from the Antimicrobial Testing Leadership and Surveillance database. Cryptococcus isolates were collected from samples of blood and cerebrospinal fluid (CSF) from patients hospitalized in different regions worldwide. We applied the epidemiological cutoff values (ECVs) of antifungals against various Cryptococcus species to distinguish wild-type (WT) from non-WT Cryptococcus isolates. A total of 395 isolates of Cryptococcus species cultured from blood (n = 201) or CSF (n = 194) were analyzed. C. grubii (n = 270), C. neoformans (n = 111), and C. gattii (n = 11) were the three predominant species causing bloodstream infections (BSI) or meningitis/meningoencephalitis (MME). The proportion of MICs above the ECV (1 mg/L) for amphotericin B among C. neoformans isolates was significantly lower than that among C. gattii isolates (MICs >0.5 mg/L; P < 0.001), as evaluated using the chi-square test. For most isolates of the three predominant Cryptococcus species, the MICs of new triazoles were ≤0.25 mg/L. The MICs of fluconazole and amphotericin B in the BSI/MME-causing Cryptococcus isolates collected from patients hospitalized in the Asia-Western Pacific region and Europe were significantly lower (i.e., the distributions were more leftward) than those in North America and Latin America. Ongoing monitoring of MIC data for important antifungals against cryptococcosis is crucial.

Coronavirus disease 2019 (COVID-19) had caused a worldwide pandemic with public health emergencies since 2020. For the symptomatic patients, high mortality rate was observed if without timely and optimized management. In this study, we aimed to investigate the predictive and prognostic roles of hematologic and biochemical parameters obtained in the emergency department (ED) for COVID-19 patients. We conducted a retrospective study in a dedicated COVID-19 medical center, recruiting a total of 228 COVID-19 patients with 86 severe and 142 non-severe cases. Both the hematologic and biochemical parameters obtained in the ED upon arrival were analyzed to evaluate the association of the biomarkers with disease severity and prognosis among COVID-19 patients. Among these parameters, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), ferritin, and D-dimer were significantly higher in the severe group than the non-severe one, whereas the platelet count and lymphocyte-to-monocyte ratio were significantly lower. Receiver operating characteristic curve analysis revealed that the areas under curve of CRP, PCT, LDH, ferritin, D-dimer, and NLR for differentiating the severity of COVID-19 were 0.713, 0.755, 0.763, 0.741, 0.733, and 0.683, respectively, whereas the areas under curve of CRP, PCT, LDH, ferritin, D-dimer, and NLR for differentiating the mortality of COVID-19 were 0.678, 0.744, 0.680, 0.676, 0.755, and 0.572, respectively. Logistic regression analysis revealed that CRP, PCT, LDH, ferritin, D-dimer, and NLR were independent indicators for prediction of severe COVID-19, and LDH and ferritin were independent factors associated with the mortality in COVID-19. In conclusion, higher CRP, PCT, LDH, ferritin, D-dimer, and NLR were associated with severe COVID-19, whereas higher LDH and ferritin were associated with the mortality in COVID-19. These findings could help early risk stratification in the ED and contribute to optimized patient management.

Background: Single dose hepatitis A virus (HAV) vaccine had been proven its efficacy in immunocompetent but not immunocompromised hosts. We aim to investigate the effectiveness of one dose versus 2 doses HAV vaccine among people living with HIV (PLHIV). Method: We conducted a 1:1 single center retrospective case-control study for PLHIV in Northern Taiwan. Case patients were those who received single dose HAV vaccine and controls were those who completed standard 2 doses HAV vaccine. Nationwide campaign of single dose HAV vaccine had been practiced for high risk population including PLHIV and those who had newly diagnosed sexually transmitted diseases. Results: During February 2016 and December 2017, 90 cases received single dose HAV vaccine provided while the other 90 age-matched controls received 2 doses vaccine were enrolled. We found more injection drug users (22.22% vs. 1.11%, p < 0.0001), more co-infection with viral hepatitis C (28.89% vs. 5.56%, p < 0.0001), and history of syphilis infection (56.67% VS 30%, p = 0.0003) in single dose group than 2 doses group. Seroconversion rate at one year was significantly higher in 2 doses group (97.78% vs 56.67%, p < 0.0001). Among single dose group, people with hepatitis B or C virus co-infection (HBV: p = 0.02, aOR: 0.03, 95% CI: 0.002-0.55; HCV: p = 0.002, aOR: 0.22, 95% CI: 0.08-0.58) were less likely to achieve seropositivity, while those who had higher CD4 count at baseline and one year, had better response to vaccine. Conclusion: Two doses HAV vaccine is necessary among PLHIV to achieve sustained seroresponse rather than single dose.

Graphene oxide (GO) composites with various metal nanoparticles (NPs) are attracting increasing interest owing to their broad scope in biomedical applications. Here, microwave-assisted chemical reduction was used to deposit nano-silver and zinc oxide NPs (Ag and ZnO NPs) on the surface of reduced GO (rGO) at the following weight percentages: 5.34% Ag/rGO, 7.49% Ag/rGO, 6.85% ZnO/rGO, 16.45% ZnO/rGO, 3.47/34.91% Ag/ZnO/rGO, and 7.08/15.28% Ag/ZnO/rGO. These materials were tested for antibacterial activity, and 3.47/34.91% Ag/ZnO/rGO and 7.08/15.28% Ag/ZnO/rGO exhibited better antibacterial activity than the other tested materials against the gram-negative bacterium Escherichia coli K12. At 1000 ppm, both these Ag/ZnO/rGO composites had better killing properties against both E. coli K12 and the gram-positive bacterium Staphylococcus aureus SA113 than Ag/rGO and ZnO/rGO did. RedoxSensor flow cytometry showed that 3.47/34.91% Ag/ZnO/rGO and 7.08/15.28% Ag/ZnO/rGO decreased reductase activity and affected membrane integrity in the bacteria. At 100 ppm, these two composites affected membrane integrity more in E. coli, while 7.08/15.28% Ag/ZnO/rGO considerably decreased reductase activity in S. aureus. Thus, the 3.47/34.91% and 7.08%/15.28% Ag/ZnO/rGO nanocomposites can be applied not only as antibacterial agents but also in a variety of biomedical materials such as sensors, photothermal therapy, drug delivery, and catalysis, in the future.

BACKGROUND/PURPOSE:This study investigated the distribution and persistence of multidrug resistant organisms (MDROs) including methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and multidrug-resistant Acinetobacter baumannii (MDRAB) in six long-term care facilities (LTCFs).METHODS:We investigated the distribution of MDROs in residents of six LTCFs and their environments from January to December 2016 (intervention period). Active surveillance of colonization of MDROs was performed by culturing rectal and nasal swab samples from the residents every three months. Multilocus sequence typing (MLST) was conducted, and genes for panton-valentine leukocidin (PVL) from MRSA isolates were determined.RESULTS:A total of 521 samples were positive for MDROs, and MRSA was the most common organism (65.1%), followed by MDRAB (11.3%), carbapenem-resistant Klebsiella pneumoniae (11.1%), carbapenem-resistant Escherichia coli (4.6%), and carbapenem-resistant P. aeruginosa (2.1%, n = 11). By a linear regression model, positive MRSA isolates from the environment were found to be statistically significant and associated with the number of colonized LTCF residents (p = 0.01), while the timing of the surveillance culture was not (p = 0.227). The main MLST types associated with PVL-production were sequence type (ST) 59, (40.0%, 24/60), ST30 (21.4%, 3/14), ST8 (87.5%, 14/16), and ST45 (3.6%, 1/28). The susceptibility rates of tetracycline (96.7%), trimethoprim-sulfamethoxazole (96.7%), and ciprofloxacin (81.7%) were statistically significant and higher in MRSA ST59, compared to the rates in MRSA ST45 isolates.CONCLUSIONS:MRSA was the most commonly colonized MDRO, both in the LTCF residents and in the environment, followed by MDRAB and carbapenem-resistant K. pneumoniae.

Rapid bacterial antibiotic susceptibility test (AST) and minimum inhibitory concentration (MIC) measurement are important to help reduce the widespread misuse of antibiotics and alleviate the growing drug-resistance problem. We discovered that, when a susceptible strain of Staphylococcus aureus or Escherichia coli is exposed to an antibiotic, the intensity of specific biomarkers in its surface-enhanced Raman scattering (SERS) spectra drops evidently in two hours. The discovery has been exploited for rapid AST and MIC determination of methicillin-susceptible S. aureus and wild-type E. coli as well as clinical isolates. The results obtained by this SERS-AST method were consistent with that by the standard incubation-based method, indicating its high potential to supplement or replace existing time-consuming methods and help mitigate the challenge of drug resistance in clinical microbiology.

Background/PurposePatients with undetected bacteremia when discharged from a hospital are considered to have occult bacteremia. Klebsiella pneumoniae bacteremia (KPB) is endemic to Taiwan. Our purpose was to study the impact of occult KPB.MethodsWe retrospectively reviewed the records of patients who were discharged from our emergency department (ED) and subsequently diagnosed with KPB (occult bacteremia), from January 2008 to March 2014. All patients are followed for at least 3 months after the index ED visit. The study group was compared to KPB patients who were directly hospitalized (DH) from ED in 2008. Thirty-day mortality was the primary endpoint.ResultsA total of 913 patients were admitted to our ED with KPB, and 88 of these patients (9.6%) had occult KPB. Among them, 43 had second ED visit and 41 were admitted. The overall 30-day mortality was 2.3%. Relative to patients with occult KPB, DH patients had more respiratory tract infections (p < 0.001) but fewer other intra-abdominal infections (p = 0.015). Liver abscess was the major diagnosis for the second ED visit (37.2%). DH patients had significantly greater 30-day mortality than that of overall patients with KPB (19.2% vs.2.3%, p < 0.001).ConclusionMost patients with occult KPB had favorable outcomes, but about half of them required a second ED visit. Clinicians should aggressively follow patients with occult KPB and should seek to identify the focus of infection in this endemic area.

Fluoroquinolone-resistant staphylococci (FQRS) are primarily selected in the nasal microbiota during fluoroquinolone (FQ) treatment. To gain insight into the dynamics of the emergence of FQRS, 49 hospitalised patients (HPs) and 62 community patients (CPs) treated with FQs were studied. Nasal swabs were collected before (T0), at the end of (T1) and 1 month after (T2) FQ treatment. FQRS were identified by mass spectrometry. Antibiotic resistance was determined. Pre- and post-exposure staphylococci populations were compared phenotypically and by MLST to determine the origin of FQRS. At T0, 33/49 HPs (67%) and 24/62 CPs (39%) carried FQRS (OR = 3.3, 95% CI: 1.4–7.9; P < 0.001). Among patients with no FQRS at T0, 15/16 HPs (94%) and 16/38 CPs (42%) had FQRS detected at T1 and/or T2 (OR = 19.6, 95% CI: 2.5–902; P < 0.001). Among FQRS having emerged, co-resistance to meticillin was detected in 87% and 82% of HPs and CPs, respectively. No selection of resistance emerging from the initial microbiota was evidenced. FQRS showed decreased species diversity in favour of Staphylococcus haemolyticus and Staphylococcus epidermidis. As a consequence of FQ treatment, acquisition of FQRS in the nasal microbiota is frequent in the community and almost inevitable in hospitals. Acquisition from extranasal sites prevails. A restriction in species diversity in favour of more pathogenic and resistant species occurs. This highlights the major impact of FQ treatment on nasal microbiota, the role of the ecological environment in the emergence of FQRS, and the high-risk of dissemination of resistant staphylococci.

This study was intended to investigate the trend in vancomycin susceptibility and correlation with molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) causing invasive infections. A total of 670 MRSA isolates were collected from patients with invasive infections as part of bacterial collection in the Tigecycline in vitro Surveillance in Taiwan (TIST) from 2006 to 2010. MICs of the isolates to vancomycin were determined using the agar dilution method. Characteristics of staphylococcal cassette chromosome mec (SCCmec), mec-associated hypervariable region (dru), and accessory gene regulator (agr) of the isolates were identified by polymerase chain reaction methods. MRSA isolates with SCCmec types I, II, and III were molecularly defined as hospital-associated MRSA (HA-MRSA), and those with SCCmec types IV, V, and VT were assigned as community-associated MRSA (CA-MRSA). All but 1 MRSA isolates exhibited vancomycin MICs ≤1 mg/L. A declining trend in vancomycin MICs among MRSA isolates was noted, which was associated with the decline in proportion of HA-MRSA. The percentage of CA-MRSA increased from 25.6% in 2006 to 46.0% in 2010. An increase in the geometric mean of vancomycin MICs was found in MRSA with particular molecular types such as SCCmec types II and III, agr groups I and II, and dru10-14. A significant correlation among particular molecular types was found, including SCCmecII-agr group II-dru4, SCCmecIII-agr group I-dru11-14, SCCmecIV-agr group II-dru9, and SCCmecVT-agr group I-dru9 and dru11. There was no vancomycin creep among MRSA isolates, and the declining trend of vancomycin MIC against MRSA was attributed to the increasing prevalence of CA-MRSA over time.

We used the Sensititre YeastOne (SYO) method (Trek Diagnostic Systems) to determine the MICs of nine antifungal agents against 474 nonduplicate blood Candida isolates. The MIC results were interpreted according to updated clinical breakpoints (CBPs) recommended by the Clinical and Laboratory Standards Institute (CLSI; document M27-S4) or epidemiology cutoff values (ECVs). The rates of fluconazole susceptibility were 99.2% (234/236) in Candida albicans, 86.7% (85/98) in C. tropicalis, and 97.7% (42/43) in C. parapsilosis. Among the 77 isolates of C. glabrata, 90.9% showed dose-dependent susceptibility (S-DD) to fluconazole. Nearly all isolates of C. albicans, C. parapsilosis, and C. krusei were susceptible to voriconazole; however, rates of voriconazole susceptibility were 78.6% in C. tropicalis. Few isolates of C. albicans (n = 5; 2.1%) and C. glabrata (n = 3; 3.9%), no isolates of C. parapsilosis, C. krusei, and C. guilliermondii, but 62.2% (n = 51) of C. tropicalis isolates were non-wild type for posaconazole susceptibility. For itraconazole susceptibility, 98.3% of C. albicans isolates were wild type, and 3.9% (n = 3) of C. glabrata isolates were non-wild type. Almost all of the isolates tested (>97% for all species) were susceptible to both micafungin and anidulafungin. All isolates tested were found to be wild type for amphotericin B susceptibility, with MICs of <1 μg/ml. Further evaluation is needed to establish CBPs of antifungal agents by the 24-h SYO method for the management of patients with candidemia or other invasive candida infections.

BACKGROUND/PURPOSE:There are only three case reports of adult patients with spontaneous Pantoea agglomerans bacteremia in the English literature. The aim of this study was to investigate clinical and microbiologic characteristics patients of P agglomerans bacteremia.METHODS:We studied all adult patients with P agglomerans bacteremia at a medical center from 2000 to 2010. The isolates were identified using two commercial identification systems.RESULTS:Of the 18 patients identified, 72% (n = 13) had active gastroesophageal disease treated with antacids. Two-thirds of patients had indwelling central lines and advanced cancers. None of the removed catheter tips yielded P agglomerans and line persistence was not associated with adverse outcomes. Initial disease severity was low, hypotension was uncommon and no patient died of bacteremia. Recurrence of bacteremia occurred in one patient with deep-seated infection. 16srRNA gene sequencing identified only half of the isolates as P agglomerans. The remaining nine isolates were Enterobacter species for six, Pantoea ananatis for two, and Exiguobacterium profundum for one. There were no significant differences between the characteristics of the subgroup molecularly identified as P agglomernas and the overall group characteristics. Eleven (61%) of the 18 isolates were susceptible to cefazolin, six (33%) susceptible to fosfomycin (MIC ≤ 64 mg/ml). Two isolates had colistin MICs ≥ 4 mg/ml.CONCLUSION:Bacteremia caused by P agglomerans is associated with gastroesophageal reflux disease and receipt of antacids. 16srRNA gene sequencing should not be used as the sole basis for its identification and we have highlighted the need for another molecular-based technique to conclusively characterize P agglomerans.

OBJECTIVESTo investigate the in vitro susceptibility of ertapenem-non-susceptible Enterobacteriaceae (ENSE) isolates to cefotaxime, ceftazidime, cefepime and aztreonam.METHODSClinical isolates of ENSE tested in this study were obtained from 10 major teaching hospitals in Taiwan during the period January 2008 to October 2010. MICs of ertapenem, cefotaxime, ceftazidime, cefepime and aztreonam were determined by the agar dilution method and were interpreted based on 2011 MIC interpretive criteria recommended by the CLSI and EUCAST.RESULTSA total of 412 non-duplicate ENSE isolates (with ertapenem MIC values ≥ 0.5 mg/L) were tested. These comprised 72 isolates of Escherichia coli [28 (38.9%) were extended-spectrum β-lactamase (ESBL)-producing isolates], 167 isolates of Klebsiella pneumoniae [74 (44.3%) were ESBL-producing isolates], 115 isolates of Enterobacter cloacae, 13 isolates of Enterobacter aerogenes, 20 isolates of Citrobacter freundii and 25 isolates of Serratia marcescens. According to 2011 CLSI (EUCAST) MIC interpretive breakpoints for Enterobacteriaceae, 64% (31%) of all ENSE isolates, 45.8% (16.7%) of E. coli isolates, 53% (29.3%) of K. pneumoniae isolates and 86.1% (35.7%) of E. cloacae isolates were susceptible to cefepime. As for ESBL-producing ENSE isolates, 25% and 14.3% of E. coli isolates and 36.5% and 10.8% of K. pneumoniae isolates were susceptible to cefepime based on CLSI and EUCAST criteria, respectively.CONCLUSIONSCefepime exerts in vitro antimicrobial activity against a significant portion of clinical isolates of ENSE, although there are discrepancies between results obtained using the CLSI-2011 and EUCAST-2011 guidelines.