Clinical effectiveness of beta-lactams versus fluoroquinolones as empirical therapy in patients with diabetes mellitus hospitalized for urinary tract infections: A retrospective cohort study.

BACKGROUND: Diabetic patients are at risk of severe urinary tract infections (UTIs). Due to the emerging resistance rates to fluoroquinolones and ß-lactams, we aimed to evaluate the effectiveness of ß-lactams versus fluoroquinolones as empirical therapy for diabetic patients hospitalized for UTIs. METHODS: A retrospective cohort study was conducted in a medical center in Taiwan between 2016 and 2018. Patients with type 2 diabetes, aged ≥20 and hospitalized for UTIs were enrolled. Patients with UTI diagnosis within one year before the admission, co-infections at the admission, or ≥2 pathogens in the urine cultures were excluded. The primary outcome was empiric treatment failure. RESULTS: 298 patients were followed for at least 30 days after the admission. Escherichia coli (61.07%) was the most common pathogen. The resistance rates of the pathogens to levofloxacin were 28.52% and 34.22% according to the historical Clinical and Laboratory Standards Institute (CLSI) breakpoints and the updated 2019 CLSI breakpoints, respectively. The resistance rates of ceftazidime and cefepime were 21.81% and 11.41%, respectively. Empirical ß-lactams were associated with less treatment failure compared to fluoroquinolones (adjusted OR = 0.32, 95% CI = 0.17-0.60). Beta-lactams were associated with less treatment failure than fluoroquinolones when appropriatness was determined by the pre-2019 CLSI breakpoints but not the 2019 CLSI breakpoints. CONCLUSIONS: In diabetic patients hospitalized for UTIs, ß-lactams were associated with less empiric treatment failure compared to fluoroquinolones when the resistance rate to fluoroquinolone is higher than ß-lactams. The updated 2019 CLSI breakpoint for fluoroquinolone was better than pre-2019 CLSI breakpoints to correlate with treatment outcomes for hospitalized UTIs in diabetic patients.

In Vitro and In Vivo Evaluations of ß-Lactam/ß-Lactamase Mono- and Combined Therapies against Carbapenem-Nonsusceptible Enterobacteriaceae in Taiwan.

Increasing carbapenem resistance rates worldwide underscored the urgent need of novel antimicrobials. Ceftazidime-avibactam and aztreonam-avibactam combinations are developed to combat carbapenem resistance, but biological and geographic variations must be considered for antibiotic susceptibility patterns varied. Thus, we sought to assess the susceptibilities of ceftazidime-avibactam and aztreonam-avibactam against 660 carbapenem-nonsusceptible Enterobacteriaceae isolates (472 Klebsiella pneumoniae and 188 Escherichia coli) collected during an earlier Taiwan surveillance study. Agar dilution method was used to determine ceftazidime-avibactam and aztreonam-avibactam susceptibility. Metallo-carbapenemase's contribution to resistance were investigated with EDTA addition. The in vivo efficacies were evaluated using a Caenorhabditis elegans model. High susceptibility rates were observed for ceftazidime-avibactam and aztreonam-avibactam against the 472 carbapenem-nonsusceptible K. pneumoniae (CnsKP) (85.2% and 95.3%, respectively) and 188 carbapenem-nonsusceptible E. coli (CnsEC) isolates (91.5% and 94.1%, respectively). For non-metallo-carbapenemase producers, the susceptibility rates for ceftazidime-avibactam were 93.6% for CnsKP and 97.7% for CnsEC, whereas only 7.1% CnsKP and 11.1% CnsEC in metallo-carbapenemase producers were susceptible to ceftazidime-avibactam. Of all isolates, 95.3% CnsKP and 94.1% CnsEC were susceptible to aztreonam-avibactam. In C. elegans model, ceftazidime-avibactam and aztreonam-avibactam revealed effective against a blaKPC-producing K. pneumoniae isolate in vivo. Our results propose a positive therapeutic approach for both combinations against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan.

Treatment of pulmonary disease caused by Mycobacterium kansasii.

As a cause of lung disease (LD), Mycobacterium kansasii is regarded as a highly virulent species among nontuberculous mycobacteria (NTM). Both the frequency of M. kansasii isolates and global prevalence of M. kansasii-LD have increased gradually over recent decades. Treatment of M. kansasii-LD is recommended because of the disease's poor prognosis and fatal outcome. The decision on the optimal time point for treatment initiation should be based on both the benefits and risks posed by multiple antimicrobial agents. For treatment-naïve patients with M. kansasii-LD, rifampin-containing multiple antimicrobial regimens for ≥12 months after culture negative conversion are effective. However, some challenges remain, such as determining the precise length of treatment duration as well as addressing intolerable adverse effects, the uncertain effectiveness of isoniazid and ethambutol in treatment, the uncertain correlation between in vitro drug susceptibility testing and clinical outcomes, and the increasing prevalence of clarithromycin-resistant M. kansasii isolates. Short-course and effective therapies must be developed. New candidate drugs, such as tedizoid and clofazimine, exhibit excellent antimycobacterial activity against M. kansasii in vitro, but in vivo studies of their clinical applications are lacking. This paper reviews the treatment, outcomes and future directions in patients with M. kansasii-LD.

Association of bacterial genotypes and epidemiological features with treatment failure in hemodialysis patients with methicillin-resistant Staphylococcus aureus bacteremia.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) infections in the hemodialysis (HD) population are epidemiologically classified as healthcare-associated infections. The data about the clinical impact and bacterial characteristics of hospital-onset (HO)- and community-onset (CO)-MRSA in HD patients are scarce. The current study analyzed the difference in the clinical and molecular characteristics of HO-MRSA and CO-MRSA. METHODS: We performed a retrospective review and molecular analysis of clinical isolates from 106 HD patients with MRSA bacteremia from 2009 to 2014. CA genotypes were defined as isolates carrying the SCCmec type IV or V, and HA genotypes were defined as isolates harboring SCCmec type I, II, or III. RESULTS: CO-MRSA infections occurred in 76 patients, and 30 patients had HO-MRSA infections. There was no significant difference in the treatment failure rates between patients with CO-MRSA infections and those with HO-MRSA infections. CA genotypes were associated with less treatment failure (odds ratio [OR]: 0.18; 95% confidence interval [95% CI], 0.07-0.49; p = 0.001). For isolates with a vancomycin minimum inhibitory concentration (MIC) < 1.5 mg/L, the multivariate analysis revealed that HA genotypes and cuffed tunneled catheter use were associated with treatment failure. For isolates with a vancomycin MIC ≥1.5 mg/L, the only risk factor for treatment failure was a higher Pitt score (OR: 1.76; 95% CI, 1.02-3.05; p = 0.043). CONCLUSION: CA genotypes, but not the epidemiological classification of CO-MRSA, impacted the clinical outcome of MRSA bacteremia in the HD population.

Treatment outcome of non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae infections: a multicenter study in Taiwan.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with high mortality, and experiences with its treatment are usually based on carbapenemase-producing strains. Non-carbapenemase-producing CRKP is of clinical significance, but relevant studies are lacking. This nationwide study aimed to evaluate the outcome of antimicrobial therapy in patients with non-carbapenemase-producing CRKP infections. Patients with non-carbapenemase-producing CRKP infections were enrolled from 16 hospitals during January 2013 to December 2014 in Taiwan. Carbapenem resistance was defined as reduced susceptibility with a minimum inhibitory concentration of ≥2 mg/L for imipenem or meropenem. The resistance mechanisms of CRKP isolates were analyzed, and the clinical data of these patients were collected retrospectively. Independent risk factors of 14-day morality were determined by Cox regression analysis. A total of 99 patients with non-carbapenemase-producing CRKP infections were enrolled, and 14-day mortality was 27.3%. Among 67 patients treated with appropriate antimicrobial therapy, most (n = 61) patients received monotherapy. The 14-day mortality was lower in patients treated with appropriate monotherapy (21.3%) than in those with inappropriate therapy (37.5%). The multivariate regression model identified monotherapy (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.13-0.71; P = 0.005) as protective factor, and APACHE II scores (HR, 1.09; 95% CI, 1.01-1.18; P = 0.022) as risk factor associated with 14-day mortality. Tigecycline, colistin, and carbapenem were the most commonly used drugs in monotherapy. This study provides evidence supporting the efficacy of monotherapy in the treatment of non-carbapenemase-producing CRKP infections, and provides a future target for antibiotics stewardship for CRKP infection.

Resistance to first- and second-line antituberculosis drugs in Southern Taiwan: Implications for empirical treatment.

BACKGROUND: Multidrug-resistant and extensively drug-resistant tuberculosis infections cause public health concerns worldwide. Local epidemiologic data about the drug resistance of Mycobacterium tuberculosis isolate (Mtb) is critical to guide appropriate empirical therapy to cure patients and restrain the spread of tuberculosis. METHODS: Antituberculosis susceptibility testing was performed for 287 Mtbs, including 63 MDR-Mtbs collected in southern Taiwan from 2011 to 2015. Tuberculosis patients were classified into newly diagnosed cases and previously treated cases based on patients' medical history. RESULTS: Almost no resistance was found to the tested second-line antituberculosis drugs in non-MDR-Mtbs. Higher resistance rates to ethambutol, ofloxacin, and streptomycin were observed in MDR-Mtbs compared to non-MDR-Mtbs. Among 63 MDR-Mtbs, 61.9% of patients were newly diagnosed and 38.1% were previously treated cases. For MDR-Mtb, the drug-resistance rates in previously treated cases were significantly higher for ethambutol, pyrazinamide, ofloxacin, moxifloxacin, streptomycin, and p-aminosalicylic acid. When MDR-Mtbs are identified in previously treated cases, empirical administration of ethambutol, pyrazinamide, ofloxacin, or moxifloxacin may not provide effective treatment. The resistance rates to these drugs were all more than 50%. Furthermore, 25% of MDR-Mtbs from previously treated patients were resistant to p-aminosalicylic acid. CONCLUSION: We observed almost no resistance to the tested second-line antituberculosis drugs among non-MDR-Mtbs. Anti-tuberculosis regimen with pyrazinamide, ethambutol, fluoroquinolone, kanamycin, cycloserine and p-aminosalicylic acid can be empirically used for newly diagnosed MDR-TB cases. For previously treated MDR-TB patients, empirical ethambutol, pyrazinamide, ofloxacin, or moxifloxacin may not provide effective treatment because the resistance rates to these drugs were all >50%.

[Sleep Quality, Depression, Anxiety, and Self-Esteem in People Living With HIV/AIDS (PLWHA)].

BACKGROUND: HIV has become a chronic disease. Therefore, the mental health and sleep quality of people living with HIV/AIDS (PLWHA) have become increasingly important issues of concern. PURPOSE: To explore the sleep quality, depression, anxiety, and self-esteem of PLWHA and the correlation between sleep quality and various related mental-health factors. METHODS: A cross-sectional, descriptive, correlational study was conducted at a medical center in southern Taiwan in 2013-2014. Data on the sleep quality, depression, anxiety, and self-esteem of 146 PLWHA cases were collected using a structural questionnaire (the Pittsburgh Sleep Quality Index, the Center for Epidemiologic Studies Depression Scale, Zung's Self-Administered Anxiety Scale, and Rosenberg Self-Esteem Scale). RESULTS: Three-fifths (60.3%) of the cases had poor sleep quality, 50% were inclined toward depression, and 36.3% were inclined toward anxiety, indicating that sleep quality, depression, and anxiety levels in these cases were worse than the general population. Moreover, significant correlations were identified between poor sleep quality and the variables of depression (r = .40, p < .001) and anxiety (r = .53, p < .001). Multiple variate analysis revealed that older age, subjective feelings that HIV significantly influenced personal life, anxiety, and depression were all significant predictors of sleep quality. No significant correlations were found between CD4 (cluster of differentiation 4) lymphocyte count, HIV viral load, or receiving antiretroviral therapy and the variables of sleep quality, depression, anxiety, or self-esteem. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: About half of the PLWHA cases in the present study exhibited poor sleep quality and tendencies toward depression and anxiety. Moreover, sleep quality and mental health factors were found to be not correlated with CD4 lymphocyte count, HIV viral load, or receiving antiretroviral therapy. Therefore, early evaluation of the sleep quality and mental health of people living with HIV/AIDS is recommended in order to provide holistic care.

Correlation between carbapenem consumption and resistance to carbapenems among Enterobacteriaceae isolates collected from patients with intra-abdominal infections at five medical centers in Taiwan, 2006-2010.

We investigated the trend in resistance to carbapenems among isolates of Enterobacteriaceae that had been collected from patients with intra-abdominal infections at five medical centers in Taiwan from 2006 to 2010 and evaluated the correlation between resistance to carbapenems and consumption of said agents as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). During the study period, the usage of ertapenem and that of total carbapenems (ertapenem, imipenem, and meropenem) increased significantly from 6.13 to 13.38 defined daily doses per 1000 patient-days for ertapenem and from 20.43 to 34.25 defined daily doses per 1000 patient-days for total carbapenems. The most common species were Escherichia coli (n = 1095), Klebsiella spp. (n = 663), and Enterobacter spp. (n = 202). The susceptibility of all isolates to ertapenem and to imipenem varied during the study period. For ertapenem, the rates of nonsusceptibility ranged from 3.5% to 10.3% and those for imipenem ranged from 3.5% to 10.7%. Although the use of carbapenems increased during the study period, there was no marked increase in resistance to carbapenems. Continuous monitoring of resistance trends is necessary so that antimicrobial prescription policies can be adjusted and infection control intervention programs can be implemented.

Zingiber officinale (ginger) compounds have tetracycline-resistance modifying effects against clinical extensively drug-resistant Acinetobacter baumannii.

Extensively drug-resistant Acinetobacter baumannii (XDRAB) is a growing and serious nosocomial infection worldwide, such that developing new agents against it is critical. The antimicrobial activities of the rhizomes from Zingiber officinale, known as ginger, have not been proven in clinical bacterial isolates with extensive drug-resistance. This study aimed to investigate the effects of four known components of ginger, [6]-dehydrogingerdione, [10]-gingerol, [6]-shogaol and [6]-gingerol, against clinical XDRAB. All these compounds showed antibacterial effects against XDRAB. Combined with tetracycline, they showed good resistance modifying effects to modulate tetracycline resistance. Using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method, these four ginger compounds demonstrated antioxidant properties, which were inhibited by MnO2, an oxidant without antibacterial effects. After the antioxidant property was blocked, their antimicrobial effects were abolished significantly. These results indicate that ginger compounds have antioxidant effects that partially contribute to their antimicrobial activity and are candidates for use in the treatment of infections with XDRAB.

High-level expression of ampC beta-lactamase due to insertion of nucleotides between -10 and -35 promoter sequences in Escherichia coli clinical isolates: cases not responsive to extended-spectrum-cephalosporin treatment.

Two Escherichia coli isolates were recovered from the blood of two cancer patients and were demonstrated to produce high levels of the AmpC beta-lactamase with isoelectric points of >9.0. The hypertranscription of ampC RNA was observed by Northern blot hybridization in both isolates. One isolate (isolate EC44) had a point mutation (G-->A at position -28) and insertion of thymidine between positions -20 and -19 of the ampC promoter gene (GenBank accession no. AE000487). The single nucleotide insertion of T between positions -19 and -20 created an optimal distance (17 bp) in the Pribnow box for ampC hyperproduction. The other isolate (isolate EC38) had two point mutations (G-->A at position -28 and C-->T at position +58) and a 2-base (GT) insertion between positions -14 and -15. Although the insertion of GT between positions -14 and -15 may create a new promoter next to the original promoter, cloning of the ampC region with truncated nucleotides of the original -35 region of EC38 failed to verify the hypothesis that a new promoter would be created by such a nucleotide insertion. Instead, multiple start sites for ampC transcription at -1, +1, +2, and +3 were observed in an S1 nuclease protection assay. These results suggest that the RNA polymerase is flexible in the selection of a start site in ampC hypertranscription. In conclusion, nucleotide insertions between the -35 and -10 ampC promoter sequences was the mechanism for the hyperproduction of AmpC beta-lactamase and resistance to oxyimino-cephalosporins. The failure of the two patients to respond to treatment with oxyimino-cephalosporins highlights the important role of such a resistance mechanism in the clinical setting.