Risk factors for mortality after linezolid treatment of vancomycin-resistant Enterococcus bloodstream infection.

OBJECTIVES: We analyzed the risk factors affecting linezolid treatment outcome in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). METHODS: We conducted a multicenter observational study of patients who received linezolid 600 mg every 12 hours for VRE BSI. The primary outcome was 28-day mortality. The estimated area under the concentration-time curve and trough concentration were calculated. Multivariable logistic regression was used for the outcome analysis. RESULTS: A total of 170 patients were included: 114 (67.1%) survived and 56 (32.9%) did not. A total of 26 (18.2%) isolates showed a linezolid minimum inhibitory concentration (MIC) of ≤1 mg/l, 113 (79.0%) of 2 mg/l, and 4 (2.8%) of 4 mg/l. The univariable analysis showed that the linezolid MIC and concentration-time curve/MIC were not associated with mortality (P = 0.95 and P = 0.42, respectively). After adjusting for underlying comorbidity and disease severity, the linezolid dose per body weight (LDBW), body height, and interaction between them were independent risks for mortality. Marginal analysis showed that increasing the LDBW was protective in patients with a body height <160 cm. A trough concentration of >12.2 mg/l was a risk factor for thrombocytopenia. CONCLUSION: The LDBW and body height were interactively associated with clinical outcomes of linezolid treatment for VRE BSI.

Clonality of Fluconazole-Nonsusceptible Candida tropicalis in Bloodstream Infections, Taiwan, 2011-2017.

Candida tropicalis is the leading cause of non-C. albicans candidemia in tropical Asia and Latin America. We evaluated isolates from 344 patients with an initial episode of C. tropicalis candidemia. We found that 58 (16.9%) patients were infected by fluconazole-nonsusceptible (FNS) C. tropicalis with cross resistance to itraconazole, voriconazole, and posaconazole; 55.2% (32/58) of patients were azole-naive. Multilocus sequence typing analysis revealed FNS isolates were genetically closely related, but we did not see time- or place-clustering. Among the diploid sequence types (DSTs), we noted DST225, which has been reported from fruit in Taiwan and hospitals in Beijing, China, as well as DST376 and DST505-7, which also were reported from hospitals in Shanghai, China. Our findings suggest cross-boundary expansion of FNS C. tropicalis and highlight the importance of active surveillance of clinical isolates to detect dissemination of this pathogen and explore potential sources in the community.

Prevalence, mechanisms and genetic relatedness of the human pathogenic fungus Aspergillus fumigatus exhibiting resistance to medical azoles in the environment of Taiwan.

Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the prevalence and molecular characteristics of azole-resistant A. fumigatus environmental isolates in Taiwan, an island country with increasing use of azole fungicides. Of the 2760 air and soil samples screened from 2014 to 2016, 451 A. fumigatus isolates were recovered from 266 samples and 34 isolates from 29 samples displayed resistance to medical azoles (itraconazole, voriconazole or posaconazole). The resistance prevalence was 10.9% and 7.5% in A. fumigatus-positive samples and isolates respectively. Most (29, 85.3%) azole-resistant isolates harboured TR34 /L98H mutations, which were widely distributed, clustered genetically with clinical isolates, and had growth rates that were similar to those of the wild-type isolates. Microsatellite genotyping revealed both the global spread of the TR34 /L98H isolates and the occurrence of TR34 /L98H/S297T/F495I isolates belonging to local microsatellite genotypes. AfuMDR3 and atrF, two efflux transporter genes, were constitutively upregulated in two individual resistant isolates without cyp51A mutations, highlighting their potential roles in azole resistance. These results emphasize the need for periodic environmental surveillance at the molecular level in regions in which azole fungicides are applied, and agricultural fungicide management strategies that generate less selective pressure should be investigated.

In Vitro Evaluation of Povidone-Iodine and Chlorhexidine against Outbreak and Nonoutbreak Strains of Mycobacterium abscessus Using Standard Quantitative Suspension and Carrier Testing.

Povidone-iodine (PI) and chlorhexidine (CHX) are widely used antiseptics active against conventional Staphylococcus aureus, Enterobacteriaceae, Candida species, and viruses, but their efficacy against Mycobacterium abscessus remains unproven. We determined the in vitro potency of alcoholic PI and CHX against M. abscessus subsp. abscessus (ATCC 19977), M. abscessus subsp. bolletii (BCRC 16915), and our outbreak strain of M. abscessus subsp. massiliense (TPE 101) in reference to Staphylococcus aureus (ATCC 29213) by standard quantitative suspension and carrier methods (EN 14563). By suspension, all mycobacterial strains compared to S. aureus were significantly more resistant to CHX, but not PI. By carrier, the mean logarithmic reductions (LR) achieved by PI under clean (dirty) conditions were 6.575 (2.482), 5.540 (2.298), 4.595 (1.967), and 1.173 (0.889), while those achieved by CHX under clean (dirty) conditions were 3.164 (5.445), 5.307 (2.564), 3.844 (2.232), and 0.863 (0.389) for S. aureus, M. abscessus subsp. bolletii, M. abscessus subsp. abscessus, and M. abscessus subsp. massiliense, respectively. M. abscessus subsp. massiliense (outbreak strain) was significantly more resistant than the other tested strains to PI and CHX. By both methods, the mean LR achieved by PI was higher than for CHX for all mycobacterial strains, but under dirty conditions, neither antiseptic was effectively mycobactericidal (LR < 5). These preliminary findings caution against the universal replacement of PI with CHX as the first-line skin antiseptic, since all M. abscessus isolates were resistant to CHX. More studies are needed to establish the best practice for skin antisepsis if mycobacterial infections are also to be prevented.

Excess Mortality Associated With Colistin-Tigecycline Compared With Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia: A Multicenter Prospective Observational Study.

OBJECTIVES: Since few therapeutic options exist for extensively drug resistant Acinetobacter baumannii, an emerging threat in ICUs worldwide, and comparative prospective studies of colistin-based combination therapies are lacking, our objective was to compare the outcomes of patients with extensively drug-resistant A. baumannii bacteremia, treated with colistin-carbapenem and colistin-tigecycline combinations. DESIGN: Prospective, observational, multicenter study. SETTING, PATIENTS, AND INTERVENTIONS: Adults with extensively drug-resistant A. baumannii bacteremia were prospectively followed from 2010 to 2013 at three hospitals in Taiwan. Extensively drug-resistant A. baumannii was defined as A. baumannii (genospecies 2) nonsusceptible to all drug classes except for colistin and tigecycline, and standard combination therapy as use of parenteral colistin-carbapenem or colistin-tigecycline for at least 48 hours after onset of bacteremia. MEASUREMENTS AND MAIN RESULTS: Primary outcome measure was 14-day mortality. Of the 176 episodes of extensively drug-resistant A. baumannii bacteremia evaluated, 55 patients with a median (interquartile range) age of 62 years (44-79 yr) and Sequential Organ Failure Assessment score of 9 (5-13) points received standard combination therapy: colistin-tigecycline in 29 patients and colistin-carbapenem in 26. Crude 14-day and in-hospital mortality rates for patients receiving colistin-tigecycline versus patients receiving colistin-carbapenem were 35% versus 15% (p=0.105) and 69% versus 50% (p=0.152), respectively. Breakthrough extensively drug-resistant A. baumannii bacteremia under steady state concentrations of combination therapy for colistin-tigecycline group was 18% and for colistin-carbapenem group was 0% (p=0.059). Eleven patients (20.0%) developed nephrotoxicity. After adjusting for age, sex, comorbidity, initial disease severity, loading colistin dose, polymicrobial infection, and primary infection site, excess 14-day mortality was associated with the use of colistin-tigecycline in the subgroup with tigecycline minimum inhibitory concentration greater than 2 mg/L compared with the use of colistin-carbapenem (hazard ratio, 6.93; 95% CI, 1.61-29.78; p=0.009). CONCLUSIONS: Increased 14-day mortality was associated with colistin-tigecycline therapy given tigecycline minimum inhibitory concentration greater than 2 mg/L compared with colistin-carbapenem therapy for extensively drug-resistant A. baumannii bacteremia.

Effectiveness of tigecycline-based versus colistin- based therapy for treatment of pneumonia caused by multidrug-resistant Acinetobacter baumannii in a critical setting: a matched cohort analysis.

BACKGROUND: Colistin and tigecycline have both been shown good in vitro activity among multi-drug resistant Acinetobacter baumannii (MDRAB). A comparative study of colistin versus tigecycline for MDRAB pneumonia is lacking. METHODS: The study enrolled adults with MDRAB pneumonia admitted to intensive care units at a referral medical center during 2009-2010. Since there were no standardized minimum inhibitory concentration (MIC) interpretation criteria of tigecycline against A. baumannii, MIC of tigecycline was not routinely tested at our hospital. During the study periods, MIC of colistin was not routinely tested also. We consider both colistin and tigecycline as definite treatments of MDRAB pneumonia. Patients who received tigecycline were selected as potential controls for those who had received colistin. We performed a propensity score analysis, by considering the criteria of age, gender, underlying diseases, and disease severity, in order to match and equalize potential prognostic factors and severity in the two groups. RESULTS: A total of 294 adults with MDRAB pneumonia were enrolled, including 119 who received colistin and 175 who received tigecycline. We matched 84 adults who received colistin with an equal number of controls who received tigecycline. The two well matched cohorts share similar characteristics: the propensity scores are colistin: 0.37 vs. tigecycline: 0.37, (P = .97); baseline creatinine (1.70 vs. 1.81, P = .50), and the APACHE II score (21.6 vs. 22.0, P = .99). The tigecycline group has an excess mortality of 16.7% (60.7% vs. 44%, 95% confidence interval 0.9% - 32.4%, P = .04). The excess mortality of tigecycline is significant only among those with MIC >2 µg/mL (10/12 vs. 37/84, P = .01), but not for those with MIC ≦ 2 µg/mL (4/10 vs. 37/84, P = .81). CONCLUSIONS: Our data disfavors the use of tigecycline-based treatment in treating MDRAB pneumonia when tigecycline and colistin susceptibilities are unknown, since choosing tigecycline-based treatment might result in higher mortality. The excess mortality of tigecycline-based group may be related to higher MIC of tigecycline (> 2 µg/mL). Choosing tigecycline empirically for treating MDRAB pneumonia in the critical setting should be cautious.

Combination antifungal therapy for disseminated fusariosis in immunocompromised patients : a case report and literature review.

Fusarium species are the second leading cause of disseminated mold infections in immunocompromised patients. The high mortality caused by such infections is attributed to the high resistance of Fusarium species to current antifungal agents. We report the first case of disseminated fusariosis after the use of alemtuzumab, an anti-CD52 monoclonal antibody, in a patient who presented with striking cutaneous and oral cavity lesions. Case reports of combination antifungal therapy for disseminated fusariosis in immunocompromised patients were reviewed. Among 19 published cases in the last 10 years plus this patient, the patients in 14 cases (70%) responded positively to combination antifungal therapy. A clinical response was achieved in seven cases before resolution of neutropenia.

Successful treatment of imported cerebral malaria with artesunate-mefloquine combination therapy.

Treatment of cerebral malaria with intravenous quinine is frequently associated with life-threatening cardiotoxicity. We report a case of imported cerebral malaria successfully treated with artesunate-mefloquine combination therapy. The 27-year-old woman presented with fever, sudden onset of binocular blindness and altered consciousness 10 days after a short stay in Indonesia. Hyperparasitemia with Plasmodium falciparum and P. vivax in more than 5% of red blood cells was demonstrated on peripheral blood smear. She was admitted to the intensive care unit due to shock, jaundice and acute renal failure. Because of a shortage of intravenous quinine, intravenous artesunate was given as an alternative. Her condition stabilized on the 3rd day of therapy, with resolution of fever and disappearance of parasitemia. Consolidation therapy with oral mefloquine and primaquine was then given to prevent recrudescence and relapse. The only adverse event associated with artesunate was transient reticulocytopenia, which resolved after discontinuation of therapy. Her vision completely recovered, along with renal and liver function.