Omega-3 polyunsaturated fatty acids and the psychiatric post-acute sequelae of COVID-19: A one-year retrospective cohort analysis of 33,908 patients.

BACKGROUND: Early prevention and management of psychiatric symptoms in long COVID (or post-COVID-19 conditions) are crucial for reducing long-term disability. Existing clinical guidelines recommend the use of omega-3 polyunsaturated fatty acids (PUFAs) as a promising therapeutic approach for various common psychiatric disorders due to their anti-inflammatory and neuroprotective characteristics. This study aims to investigate the potential efficacy of omega-3 PUFAs in alleviating the psychiatric sequelae following COVID-19. METHODS: This 1-year retrospective cohort study used the TriNetX electronic health records network to examine the effects of omega-3 PUFAs supplements on psychiatric sequelae in adults diagnosed with COVID-19. Using propensity-score matching, the study compared those who used omega-3 PUFAs supplements with those who did not, assessing outcomes including depression, anxiety disorders, insomnia, and other somatic conditions up to a year after COVID-19 diagnosis. RESULTS: In 16,962 patients who received omega-3 PUFAs supplements and 2,248,803 who did not, omega-3 supplementation significantly reduced the risk of developing psychiatric sequelae post-COVID-19 diagnosis (HR, 0.804; 95% CI, 0.729 to 0.888). Specifically, the risks for depression (HR, 0.828; 95% CI, 0.714 to 0.960), anxiety disorders (HR, 0.833; 95% CI, 0.743 to 0.933), and insomnia (HR, 0.679; 95% CI, 0.531 to 0.869) were reduced in the omega-3 group. This effect was consistent across sex, race, 18-59 age group, and patients with less than two doses of the COVID-19 vaccine. The omega-3 group also had a lower risk of cough and myalgia, but no significant difference was noted for other symptoms like chest pain, abnormal breathing, abdominal issues, fatigue, headache, and cognitive symptoms. CONCLUSION: Omega-3 PUFAs may require re-evaluation as a preventive strategy against adverse mental health outcomes post-COVID-19 in placebo-controlled clinical trials.

Omega-3 Polyunsaturated Fatty Acids for Core Symptoms of Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis of Randomized Controlled Trials.

Objective: Previous studies have shown conflicting results for the effectiveness of omega-3 polyunsaturated fatty acids (PUFAs) in improving attention-deficit/hyperactivity disorder (ADHD) symptoms. This inconsistency may be due to differences in dosage, composition, and treatment duration. The current meta-analysis aims to address this inconsistency by improving subtype analyses and focusing on heterogeneity in treatment duration, omega-3 PUFA composition, and eicosapentaenoic acid (EPA) dose.Data Sources and Study Selection: We searched PubMed, EMBASE, PsycINFO, and Cochrane Library for randomized controlled trials of omega-3 PUFAs for ADHD, without publication year or language limitations, up to November 27, 2022. The primary outcome was the improvement of ADHD core symptoms. Subgroup analyses were conducted based on the formula, dosages, and composition ratios of omega-3 PUFAs. To ensure methodological quality, the Cochrane Risk-of-Bias Tool 1.0 was utilized to assess the risk of bias for each study included in the analysis. The pooled data were then analyzed using the random-effect meta-analysis, and the inverse variance method was employed.Data Extraction: The outcomes of interest were extracted using a data extraction form developed for this study.Results: Twenty-two studies with 1,789 participants were included in the analysis. Overall, omega-3 PUFAs did not significantly improve ADHD core symptoms compared to placebo (standardized mean difference [SMD]: -0.16; 95% CI, -0.34 to 0.01; P = .07). However, in the subgroup of studies with a treatment duration of at least 4 months, omega-3 PUFAs were significantly more effective than placebo (SMD: -0.35; 95% CI,-0.61 to -0.09; P = .007). Neither high eicosapentaenoic acid (EPA) dosage nor high EPA/docosahexaenoic acid (DHA) ratio was found to improve ADHD symptoms.Conclusions: Our findings indicate that omega-3 PUFAs did not improve ADHD core symptoms, but long-term supplementation may have potential benefits. The main limitation of the study was the moderate heterogeneity and small sample sizes in subgroup analyses and the lack of dietary pattern information.

The clinical efficacy of cefoperazone-sulbactam versus piperacillin-tazobactam in the treatment of severe community-acquired pneumonia.

The objective was to compare the clinical efficacy of cefoperazone-sulbactam with piperacillin-tazobactam in the treatment of severe community-acquired pneumonia (SCAP). The retrospective study was conducted from March 1, 2018 to May 30, 2019. Clinical outcomes were compared for patients who received either cefoperazone-sulbactam or piperacillin-tazobactam in the treatment of SCAP. A total of 815 SCAP patients were enrolled. Among them, 343 received cefoperazone-sulbactam, and 472 received piperacillin-tazobactam. Patients who received cefoperazone-sulbactam presented with higher Charlson Comorbidity Index scores. (6.20 ± 2.77 vs 5.72 ± 2.61; P = .009). The clinical cure rates and effectiveness for patients receiving cefoperazone-sulbactam and piperacillin-tazobactam were 84.2% versus 80.3% (P = .367) and 85.4% versus 83.3% (P = .258), respectively. In addition, the overall mortality rate of the cefoperazone-sulbactam group was 16% (n = 55), which was also comparable to the piperacillin-tazobactam group (17.8%, n = 84, P = .572). The primary clinical outcomes for patients receiving cefoperazone-sulbactam were superior compared to those receiving piperacillin-tazobactam after adjusting disease severity status. The clinical efficacy of cefoperazone-sulbactam in the treatment of adult patients with SCAP is comparable to that of piperacillin-tazobactam. After adjusting for disease severity, cefoperazone-sulbactam tended to be superior to piperacillin-tazobactam.

Ceftobiprole medocaril for the treatment of pneumonia.

INTRODUCTION: Ceftobiprole, a fifth-generation cephalosporin, exhibits a broad-spectrum activity against common pathogens causing pneumonia, including multidrug-resistant organisms (MDROs), such as penicillin-resistant S. pneumoniae (PRSP) and methicillin-resistant Staphylococcus aureus (MRSA) and non-extended-spectrum ß -lactamase (non-ESBL) producing Enterobacterales strains. Therefore, ceftobiprole should be considered as a potential alternative for the empirical treatment of pneumonia in patients with high risk for MDROs. AREA COVERED: In this review, we discussed the role of ceftobiprole in the treatment of patients with pneumonia. EXPERT OPINION: Ceftobiprole has several advantages in the treatment of pneumonia. First, ceftobiprole exerts its bactericidal activity by inhibiting transpeptidases, especially showing strong affinities to penicillin-binding protein (PBP) 2a, PBP2× and PBP3. Second, its plasma protein binding is minimal, allowing it to penetrate lung tissue and achieve high concentrations in epithelial lung fluid. Third, ceftobiprole exhibits potent in vitro activity against a wide range of susceptible pathogens, including S. aureus, S. pneumoniae, Viridans streptococci, H. influenzae, M. catarrhalis, Enterobacterales, and particularly, MRSA and P. aeruginosa. Finally, several randomized controlled trials have demonstrated the clinical efficacy and safety of ceftobiprole in the treatment of pediatric and adult patients with community-acquired pneumonia and hospital-acquired pneumonia (excluding ventilator-associated pneumonia).

The Impact of 52-Week Single Inhaler Device Triple Therapy versus Dual Therapy on the Mortality of COPD Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There are more single inhaler device triple therapy available for COPD patients now. However, the effect of long-term triple therapy fixed dose combination (FDC) on mortality remains unclear. This study aimed to evaluate the impact of one-year single inhaler device triple therapy, including long-acting ß2-agonists (LABAs), long-acting muscarinic receptor antagonists (LAMAs), and inhaled corticosteroids (ICSs), with dual therapies, comprised of either LABA/LAMA or ICS/LABA, on the mortality of patients with COPD. We searched the PubMed, Cochrane library, Web of Science, Embase databases, and clinical trial registry of clinicaltrials.gov and WHO ICTRP. Randomized controlled trials (RCTs) compared single inhaler device triple and dual therapies for 52 weeks were selected for the meta-analysis. The primary endpoint was all-cause mortality. A total of 6 RCTs were selected for the meta-analysis, including 10,274 patients who received single inhaler device triple therapy (ICS/LABA/LAMA FDC) and 12,395 patients who received ICS/LABA or LABA/LAMA dual therapy. Risk of death was significantly lower in the ICS/LABA/LAMA FDC group compared to the LABA/LAMA group (RR = 0.69, 95% CI = 0.53-0.90, p = 0.007). There was no significant difference in mortality between the ICS/LABA/LAMA FDC and ICS/LABA therapy groups (RR = 0.94, 95% CI = 0.72-1.24, p = 0.66). In addition, patients receiving ICS/LABA/LAMA FDC therapy had less moderate or severe exacerbations compared with the dual therapy groups (RR = 0.76, 95% CI = 0.73-0.80, p < 0.001 for LABA/LAMA; RR = 0.84, 95% CI = 0.78-0.90, p < 0.001 for ICS/LABA). By contrast, the risk of pneumonia in the ICS/LABA/LAMA FDC group was higher than in the LABA/LAMA group (RR = 1.43, 95% CI = 1.21-1.68, p < 0.001). In conclusion, ICS/LABA/LAMA FDC therapy could help improve the clinical outcomes of patients with COPD. However, triple therapy could increase the risk of pneumonia in comparison with LABA/LAMA dual therapy.

Vitamin D supplementation and the outcomes of critically ill adult patients: a systematic review and meta-analysis of randomized controlled trials.

This meta-analysis assessed the association between vitamin D supplementation and the outcomes of critically ill adult patients. A literature search was conducted using the PubMed, Web of Science, EBSCO, Cochrane Library, Ovid MEDLINE, and Embase databases until March 21, 2020. We only included randomized controlled trials (RCTs) comparing the efficacy of vitamin D supplementation with placebo in critically ill adult patients. The primary outcome was their 28-day mortality. Overall, 9 RCTs with 1867 patients were included. In the pooled analysis of the 9 RCTs, no significant difference was observed in 28-day mortality between the vitamin D supplementation and placebo groups (20.4% vs 21.7%, OR, 0.73; 95% CI, 0.46-1.15; I2 = 51%). This result did not change as per the method of vitamin D supplementation (enteral route only: 19.9% vs 18.2%, OR, 1.19; 95% CI, 0.88-1.57; I2 = 10%; intramuscular or intravenous injection route: 25.6% vs 40.8%, OR, 0.48; 95% CI, 0.21-1.06; I2 = 19%) or daily dose (high dose: 20.9% vs 19.8%, OR, 0.83; 95% CI, 0.51-1.36; I2 = 53%; low dose: 15.6% vs 21.3%, OR, 0.74; 95% CI, 0.32-1.68; I2 = 0%). No significant difference was observed between the vitamin D supplementation and placebo groups regarding the length of ICU stay (standard mean difference [SMD], - 0.30; 95% CI, - 0.61 to 0.01; I2 = 60%), length of hospital stay (SMD, - 0.17; 95% CI, - 041 to 0.08; I2 = 65%), and duration of mechanical ventilation (SMD, - 0.41; 95% CI, - 081 to 0.00; I2 = 72%). In conclusion, this meta-analysis suggested that the administration of vitamin D did not provide additional advantages over placebo for critically ill patients. However, additional studies are needed to confirm our findings.

Lefamulin vs moxifloxacin for community-acquired bacterial pneumonia.

Lefamulin is a novel pleuromutilin antibiotic with potent in vitro activity against key community-acquired bacterial pneumonia (CABP) pathogens. However, the clinical efficacy and safety of lefamulin for treating CABP remains unclear.An integrated analysis of 2 phase III trials investigating the clinical efficacy and safety of lefamulin vs moxifloxacin in the treatment of CABP was conducted.A total of 1289 patients (lefamulin group: 646 and moxifloxacin group: 643) were included in this analysis. The early clinical response rate was 89.3% and 90.5% among lefamulin and moxifloxacin group, respectively. Lefamulin was noninferior to moxifloxacin (89.3% vs 90.5%, RR: 0.99, 95% CI: 0.95-1.02, I = 0%). In terms of clinical response at test of cure, no significant difference was observed between the lefamulin and moxifloxacin groups (for modified intention to treat population, RR: 0.98, 95% CI: 0.94-1.02, I = 0%; for clinically evaluable population, RR: 0.96, 95% CI: 0.93-1.00, I = 0%). In the subgroup analysis, the early clinical response rate at early clinical assessment and clinical response rate at test of cure of lefamulin was similar to that of moxifloxacin across different subgpopulations and all baseline CABP pathogens. Lefamulin was associated with a similar risk of adverse events as moxifloxacin.Clinical efficacy and tolerability for lefamulin in the treatment of CABP were similar to those for moxifloxacin.

In Vitro Synergy of Pongamia pinnata Extract in Combination with Antibiotics for Inhibiting and Killing Methicillin-Resistant Staphylococcus aureus.

AIMS: Currently, we face the serious problem of multiple drug-resistant pathogens. The development of new antimicrobial agents is very costly and time-consuming. Therefore, the use of medicinal plants as a source of alternative antibiotics or for enhancing antibiotic effectiveness is important. METHODS: The antibacterial effects of aqueous extracts of the seed coat of Pongamia pinnata (Linn.) Pierre in combination with several antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) were tested by broth dilution, checkerboard, and time-kill methods. RESULTS: For the combinations of P. pinnata with ampicillin, meropenem, cefazolin, cefotaxime, cefpirome, and cefuroxime, 70% to 100% were synergistic, with a fractional inhibitory concentration (FIC) index of < 0.5. For the time-kill method with 0.5× minimum inhibitory concentration (MIC) of P. pinnata in combination with 8, 4, 2, and 1 µg mL-1 of the various antibiotics, almost all of the combinations showed synergistic effects, even with the lowest concentrations of P. pinnata, except for aztreonam. No antagonistic effect was observed for these combinations. CONCLUSIONS: Based on these findings, aqueous seed coat extracts of P. pinnata have good potential for the design of new antimicrobial agents.

The effects of single inhaler triple therapy vs single inhaler dual therapy or separate triple therapy for the management of chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials.

Background: This study aims to compare the effects of single inhaler triple therapy comprised of inhaled corticosteroids (ICSs), long-acting ß2-agonists (LABAs), and long-acting muscarinic receptor antagonists (LAMAs) with dual therapies comprised of either LABA/LAMA, ICS/LABA or separate ICS/LABA plus LAMA triple therapy. Methods: The Pubmed, Embase, and Cochrane databases were searched up to October 31st 2018. Only randomized controlled trials were included in the meta-analysis. The primary outcome was the rate of moderate-to-severe chronic obstructive pulmonary disease (COPD) exacerbations. Results: Seven studies fulfilling the inclusion criteria were included in the meta-analysis. Single inhaler triple therapy was associated with a significantly lower risk of COPD exacerbation compared with LABA/LAMA (rate ratio, 0.69; 95% confidence interval [CI] 0.55 to 0.87, I2 =85%), and ICS/LABA (rate ratio, 0.81; 95% CI 0.73 to 0.89, I2 =29%) dual therapy. Single inhaler triple therapy led to a more significant improvement in lung function and quality of life compared with LABA/LAMA and ICS/LABA dual therapy. Single inhaler triple therapy was associated with a higher risk of pneumonia compared with LABA/LAMA (risk ratio, 1.38, 95% CI 1.14 to 1.67, I2 =0) dual therapy. Conclusions: The use of single inhaler triple therapy for COPD patients can result in lower rates of moderate or severe exacerbations of COPD as well as improved lung function and quality of life compared with dual therapy with LABA/LAMA or ICS/LABA.

Reactive oxygen species mediate the chemopreventive effects of syringin in breast cancer cells.

BACKGROUND: Syringin (Syr), a phenylpropanoid glycoside extracted from Eleutherococcus senticosus, possesses various biological properties, including anticancer activities. However, the cytotoxicity effects of Syr on breast cancer have not yet been elucidated. PURPOSE: In this study, we evaluated the anticancer potential of Syr on breast carcinoma and the mechanism involved. STUDY DESIGN/METHODS: Non-tumorigenic (M10), tumorigenic (MCF7) and metastatic (MDA-MB-231) breast cancer cell lines as well as xenograft model were treated with Syr. Proliferation and cell cycle distribution were evaluated using the MTT, the colony formation assay and flow cytometry. The expression levels of cytotoxicity-related proteins were detected by Western blot. RESULTS: Here, we found that colony formation inhibition, cell cycle arrest in the G2/M phase, down-regulation of X-linked inhibitor of apoptosis protein (XIAP), cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3/9 activation were observed in MCF7 and MDA-MB-231 cells treated with Syr. Moreover, pretreatment with a pan-caspase inhibitor (Z-DEVD-FMK) inhibited Syr-induced apoptosis. In addition, treatment with Syr also increased the production of reactive oxygen species (ROS). However, the antioxidant N-acetyl-cysteine (NAC) reversed the ROS levels and rescued the apoptotic changes. Meanwhile, Syr inhibited the growth of breast cancer xenograft models and dramatically decreased tumor volume without any obvious body weight loss in vivo. CONCLUSION: Our findings suggest that Syr induces oxidative stress to suppress the proliferation of breast cancer and thus might be an effective therapeutic agent to treat breast cancer.

In vitro and in vivo antibacterial activity of tigecycline against Vibrio vulnificus.

BACKGROUND/PURPOSE: The aim of this study is to investigate the role of tigecycline in Vibrio vulnificus infection. METHODS: Eight randomly selected clinical V. vulnificus isolates were studied to obtain the minimal inhibitory concentrations (MICs) of minocycline, cefotaxime, and tigecycline, and the time-kill curves of tigecycline alone or in combination with other drugs. A peritonitis mouse model was used for the evaluation of the therapeutic efficacy of tigecycline alone or cefotaxime in combination with minocycline or tigecycline. RESULTS: The MIC of minocycline, cefotaxime, and tigecycline for eight clinical V. vulnificus isolates was 0.06-0.12 µg/mL, 0.03-0.06 µg/mL, and 0.03-0.06 µg/mL, respectively. In time-killing studies, at the concentration of 1 × MIC, the inhibitory effect of tigecycline persisted for 24 hours in five of eight isolates. With 2 × MIC and trough level, the inhibitory effect was noted in all isolates for 24 hours. With the combination of minocycline plus cefotaxime and tigecycline plus cefotaxime at 1/2 × MIC, the bactericidal effect was noted in 25% and 62.5% of eight isolates and synergism in 50% and 75% of isolates. With a low (1.25 × 105 CFU/mL) inoculum, all infected mice survived with tigecycline alone, tigecycline plus cefotaxime, or minocycline plus cefotaxime on the 14th day. At the inoculum of 1.25 × 106 CFU, the survival rate was 33.3% on the 14th day in the tigecycline plus cefotaxime-treated group, but none of the mice treated by tigecycline alone or minocycline plus cefotaxime survived (33.3% vs. 0%, p = 0.01 by Fisher's exact test). CONCLUSION: Our in vitro combination and animal studies indicate that tigecycline could be an option for the treatment of invasive V. vulnificus infections.

Risk of incident active tuberculosis disease in patients treated with non-steroidal anti-inflammatory drugs: a population-based study.

BACKGROUND: Mycobacterium tuberculosis (TB) is one of the world's most devastating public health threats. Our goal is to evaluate whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) affect the risk of new incident active TB disease. METHODS: We conducted a nested case-control analysis by using a 1 million longitudinally followed cohort, from Taiwan's national health insurance research database. Effects of NSAIDs on active TB were estimated by conditional logistic regression and adjusted using a TB-specific disease risk score (DRS). NSAIDs exposures were defined as having a prescription record of NSAIDs ≧ 7 days that ended between 31 and 90 days prior to the index date. RESULTS: A total of 123,419 users of traditional NSAIDs, 16,392 users of cyclooxygenase-2 selective inhibitor (Coxibs), and 4706 incident cases of active TB were identified. Compared with nonusers, use of traditional NSAIDs was associated with an increased risk of TB in the unadjusted analysis ([RR], 1.39; 95% [CI], 1.24 - 1.57 and DRS adjusted analysis ([ARR], 1.30; 95% [CI], 1.15- 1.47). However, use of Coxibs was not associated with a significant increase in the risk of TB after DRS adjustment ([ARR], 1.23; 95% [CI], 0.89 - 1.70). CONCLUSIONS: In this large population-based study, we found that subjects using traditional NSAIDs were associated with increased risk for active TB. We did not find evidence for a causative mechanism between traditional NSAIDs and TB, and more research is required to verify whether the association between traditional NSAIDs and TB is causal, or simply reflects an increased use of anti-inflammatory drugs in the early phases of TB onset.

RNA polymerase B subunit gene mutations in biofilm-embedded methicillin-resistant Staphylococcus aureus following rifampin treatment.

BACKGROUND/PURPOSE: This study was conducted to compare the mutation rates of different rpoB sites and rifampin minimum inhibitory concentration (MIC) changes prior to and after rifampin therapy for biofilm-embedded methicillin-resistant Staphylococcus aureus (MRSA) isolates. METHODS: The screening of rifampin-resistant MRSA isolates, from the biofilm at Day 5 with or without exposure to the susceptible breakpoint concentration of rifampin recommended by the Clinical and Laboratory Standards Institute (1 mg/L), was conducted using agar plates containing rifampin. A partial fragment of RNA polymerase B subunit gene (rpoB), including clusters I and II, was amplified and sequenced. The rifampin MIC values and mutation frequencies at different sites of rpoB were measured and evaluated in rifampicin-resistant isolates. RESULTS: Rifampin-resistant mutants could be selected from all of 39 randomly selected rifampin-susceptible MRSA isolates in the biofilm model. The spontaneous mutation frequency ranged from 1.00 × 10(-4) to 3.85 × 10(-7). Mutation at codon 481 was most commonly found at 35 (89.7%) of 39 MRSA isolates. Without rifampin induction, the MIC ranged between 0.125 mg/L and1024 mg/L and mutation sites included cluster I 464, 466, 468, 471, 474, 477, 481, 484, 486 and cluster II 519, 527, 529 with the percentage of 471 (35.9%), 477 (33.3%), 481 (53.8%), and 484 (35.9%). Conversely, with the induction of rifampin, the MIC value ranged ∼256-1024 mg/L. The mutation sites that were more concentrated included 468 (17.9%), 477 (30.8%), 481 (89.7%), 484 (17.9%), and 486 (33.3%). CONCLUSION: We documented high rifampin resistance induction activity when MRSA was engaged in biofilm with rifampin exposure. Monotherapy seems to be inadequate for MRSA in biofilm. There is an urgent need for developing effective combination therapies with less rifampin resistance-inducing activities for treating MRSA in biofilms.

Decline in rates of acquired multidrug-resistant tuberculosis after implementation of the directly observed therapy, short course (DOTS) and DOTS-Plus programmes in Taiwan.

OBJECTIVES: To investigate the impact of the directly observed therapy, short course (DOTS) and DOTS-Plus strategies on changes in resistance profiles among Mycobacterium tuberculosis (MTB). METHODS: We performed a retrospective analysis of resistance profiles among isolates of MTB obtained from 2160 consecutive patients with culture-confirmed pulmonary tuberculosis (TB) between 2005 and 2011 at a referral centre in southern Taiwan. RESULTS: Of the 2160 patients, 70 (3.2%) had primary multidrug-resistant (MDR)-TB, 178 (8.2%) had acquired MDR-TB, 10 (0.5%) had primary extensively drug-resistant (XDR)-TB, 23 (1.1%) had acquired XDR-TB and 5 (0.2%) had totally drug-resistant (TDR)-TB. Trend analysis revealed that the rates of acquired MDR-TB were significantly lower after implementation of the DOTS and DOTS-Plus programmes (P < 0.01). There was a significant negative correlation between the coverage rates of the DOTS and DOTS-Plus programmes and the rates of acquired MDR-TB (r = -0.84, P = 0.02 and r = -0.92, P = 0.03, respectively). The rates of resistance to rifampicin, isoniazid, ofloxacin, moxifloxacin, levofloxacin and para-aminosalicylic acid also decreased significantly during the study period. However, the rates of primary MDR-TB remained stable (P = 0.11). Multivariate logistic regression analysis showed that age ranging from 45 to 64 years, positive acid-fast stain results at the initiation of treatment and treatment without DOTS were independent risk factors associated with acquired MDR-TB. In addition, previous treatment for TB (100% versus 19% for TDR-TB and non-TDR-TB, P < 0.01) and treatment without DOTS (80% versus 44% for TDR-TB and non-TDR-TB, P = 0.18) were risk factors for TDR-TB. CONCLUSIONS: DOTS and DOTS-Plus are both effective at preventing the acquisition of MDR-TB in Taiwan.

Impact of susceptibility profiles of Gram-negative bacteria before and after the introduction of ertapenem at a medical center in northern Taiwan from 2004 to 2010.

This retrospective observational study evaluated the impact of antimicrobial consumption on antimicrobial susceptibility among aerobic Gram-negative bacteria after introducing ertapenem to the formulary of a teaching hospital (1130 beds) in northern Taiwan. Data on consumption of various antimicrobial agents, expressed as defined daily dose/1000 patient-days (DDD/1000 PD), were collected retrospectively from hospital pharmacy records 2 years before and 5 years after the introduction of ertapenem (October 2005). During the study period, the consumption of ampicillin and aminoglycosides decreased significantly. In contrast, the consumption of cefoxitin, ceftazidime, cefpirome, piperacillin-tazobactam, carbapenems (ertapenem, imipenem, and meropenem), and fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin) increased significantly over time. There was a significant increase in the rate of susceptibility of Escherichia coli to ampicillin, cefotaxime, ceftazidime, piperacillin-tazobactam, cefpirome, amikacin, and levofloxacin; an increase in the rate of susceptibility of Klebsiella pneumoniae to ceftazidime, cefepime, cefpirome, piperacillin-tazobactam, meropenem, levofloxacin, and amikacin; a significant decrease in the rate of susceptibility of Pseudomonas aeruginosa to meropenem; and a significant decrease in the rate of susceptibility of Acinetobacter baumannii to ceftazidime, carbapenems, ciprofloxacin, and levofloxacin. The rate of antibiotic susceptibility to ertapenem of extended spectrum ß-lactamase producers, including E. coli and K. pneumoniae, remained stable. Usage of ertapenem was found to be negatively and significantly associated with the susceptibility rates of P. aeruginosa to meropenem and gentamicin. Significantly negative correlations were noted between the use of ertapenem and the rates of susceptibility of A. baumannii to ceftazidime, piperacillin-tazobactam, carbapenems (imipenem and meropenem), ciprofloxacin, and levofloxacin.

Increased rifampicin resistance in blood isolates of meticillin-resistant Staphylococcus aureus (MRSA) amongst patients exposed to rifampicin-containing antituberculous treatment.

The aim of this study was to determine the rifampicin (RIF) resistance rate of meticillin-resistant Staphylococcus aureus (MRSA) amongst patients with MRSA bacteraemia who have or have not been exposed to RIF-containing antituberculous (anti-TB) treatment. From 2000 to 2008, patients with MRSA bacteraemia and previous exposure to RIF-containing anti-TB therapy were selected. Patients matched for sex, age and time of culture of MRSA bacteraemia but without exposure to anti-TB therapy were selected as a control group. A total of 139 patients, comprising 49 with RIF exposure and 90 without RIF exposure, were analysed. The RIF resistance rate was higher in patients with previous RIF exposure (61.2% vs. 20.0%; P<0.001). The minimum inhibitory concentration of RIF that inhibited 50% of MRSA isolates (MIC(50)) for the study group was also higher (128 mg/L vs. 0.015 mg/L; P<0.001). The mortality rate was higher in the study group (59.2% vs. 41.1%; P=0.041). MRSA isolates recovered from patients with current usage of a RIF-containing anti-TB regimen were more likely to be resistant to RIF (87.5% vs. 36%; P=0.001), with higher MIC(50) values (256 mg/L vs. 1mg/L; P=0.002), and resulted in a higher mortality rate than isolates from patients with remote usage of an anti-TB regimen (79.2% vs. 40%; P=0.005). Multivariate analysis showed that current anti-TB drug usage was the only risk factor for RIF resistance [odds ratio (OR)=7.457, 95% confidence interval (CI) 1.581-35.167] and mortality (OR=7.201, 95% CI 1.583-32.766). Given the high rate of RIF resistance in patients with prior anti-TB treatment, RIF susceptibility testing should be performed before considering combination treatment of RIF in MRSA infection.