High and Increasing Oxa-51 DNA Load Predict Mortality in Acinetobacter baumannii Bacteremia: Implication for Pathogenesis and Evaluation of Therapy

BACKGROUND: While quantification of viral loads has been successfully employed in clinical medicine and has provided valuable insights and useful markers for several viral diseases, the potential of measuring bacterial DNA load to predict outcome or monitor therapeutic responses remains largely unexplored. We tested this possibility by investigating bacterial loads in Acinetobacter baumannii bacteremia, a rapidly increasing nosocomial infection characterized by high mortality, drug resistance, multiple and complicated risk factors, all of which urged the need of good markers to evaluate therapeutics. METHODS AND FINDINGS: We established a quantitative real-time PCR assay based on an A. baumannii-specific gene, Oxa-51, and conducted a prospective study to examine A. baumannii loads in 318 sequential blood samples from 51 adults patients (17 survivors, 34 nonsurvivors) with culture-proven A. baumannii bacteremia in the intensive care units. Oxa-51 DNA loads were significantly higher in the nonsurvivors than survivors on day 1, 2 and 3 (P=0.03, 0.001 and 0.006, respectively). Compared with survivors, nonsurvivors had higher maximum Oxa-51 DNA load and a trend of increase from day 0 to day 3 (P<0.001), which together with Pitt bacteremia score were independent predictors for mortality by multivariate analysis (P=0.014 and 0.016, for maximum Oxa-51 DNA and change of Oxa-51 DNA, respectively). Kaplan-Meier analysis revealed significantly different survival curves in patients with different maximum Oxa-51 DNA and change of Oxa-51 DNA from day 0 to day 3. CONCLUSIONS: High Oxa-51 DNA load and its initial increase could predict mortality. Moreover, monitoring Oxa-51 DNA load in blood may provide direct parameters for evaluating new regimens against A. baumannii in future clinical studies

Impact of first-line protease inhibitors on predicted resistance to tipranavir in HIV-1-infected patients with virological failure

<p>Abstract</p> <p>Background</p> <p>Tipranavir (TPV) is a recently approved nonpeptidic protease inhibitor (PI) of HIV-1 and has been indicated for those infected with PIs-resistant HIV-1. However, in clinical practice, whether the HIV-1 from the patients with virological failure to the regimens containing first-line PIs remains susceptible to TPV/r may be questionable.</p> <p>Methods</p> <p>To assess the resistance levels to TPV of HIV-1 from patients with treatment failure to first-line PIs, patients who experienced virological failure were tested for genotypic resistance of HIV-1 since August 2006 in National Taiwan University Hospital. Patients were enrolled for this analysis if their failed regimens contained > 12 weeks of atazanavir or lopinavir/ritonavir (defined as ATV group and LPV/r group, respectively), but were excluded if they experienced both or other PIs. The levels of genotypic resistance to TPV/r were determined by TPV mutation score.</p> <p>Results</p> <p>Till May 2008, 21 subjects in ATV group and 20 subjects in LPV/r group were enrolled. The TPV mutation scores in subjects in LPV/r group were significantly higher than these in ATV group (median, 3 vs 1, P = 0.007). 95.2% subjects in ATV group and only 45% subjects in LPV/r group had an estimated maximal virological response to TPV/r (P < 0.001). The resistance levels to TPV/r correlated with the duration of exposure to first-line PIs, whether in ATV or LPV/r group.</p> <p>Conclusion</p> <p>Cross-resistance from first-line PIs may impede the effectiveness of TPV/r-containing salvage therapy. TPV/r should be used cautiously for patients with virological failure to LPV/r especially long duration of exposure.</p

Nosocomial methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in Taiwan: Mortality analyses and the impact of vancomycin, MIC = 2 mg/L, by the broth microdilution method

<p>Abstract</p> <p>Background</p> <p>Previous studies regarding the prognosis of patients infected with MRSA isolates characterized by a high minimum inhibitory concentration (MIC) for vancomycin have generally used a commercial Etest. Little research has been conducted on determining the vancomycin susceptibility of MRSA using a reference microdilution. Additionally, there is discordance between the MIC result from an Etest and the value determined using the reference microdilution method.</p> <p>Methods</p> <p>Using a reference microdilution method, we determined the MIC of vancomycin for isolates from 123 consecutive patients with nosocomial MRSA bacteremia. The clinical features and outcome for these patients were recorded and the MRSA isolates were genotyped.</p> <p>Results</p> <p>Among the 123 non-duplicated isolates, 21.1% had a MIC = 2 mg/L, 76.4% had a MIC = 1 mg/L and 2.4% had MIC = 0.5 mg/L. Patients with MRSA bacteremia in the ICU or those who had been hospitalized for a long time were more likely to be infected with strains of high vancomycin MIC MRSA (MIC = 2 mg/L; <it>p </it>< 0.05). Cox regression analysis demonstrated that the high MIC group had a significantly higher 30-day mortality than the low MIC group (HR: 2.39; 95% CI: 1.20-4.79; <it>p </it>= 0.014). Multivariate analyses indicated that the presence of high MIC isolates, pneumonia, post-cardiothoracic surgery and a high Charlson comorbidity index were all independent predictors of a 30-day mortality. Genotyping of these high vancomycin MIC isolates demonstrated that SCC<it>mec </it>III, <it>spa </it>type037, was the predominant strain (> 80%). The rates of resistance to trimethoprim/sulfamethoxazole, gentamicin, levofloxacin, rifampin and tetracycline were also higher in the high MIC group than in the isolates belonging to low MIC group (<it>p </it>< 0.05).</p> <p>Conclusions</p> <p>In a high vancomycin MIC group in Taiwan, SCC<it>mec </it>III, <it>spa </it>type t037, was the predominant strain of MRSA identified. Patients with MRSA bacteremia in the ICU or who had prolonged hospitalization were more likely to be infected with <it>S. aureus </it>strains with high vancomycin MICs. The mortality rate was higher among patients infected with these strains compared to patients infected with low MIC strains.</p

In vitro activity of linezolid, tigecycline, and daptomycin on methicillin-resistant Staphylococcus aureus blood isolates from adult patients, 2006–2008: Stratified analysis by vancomycin MIC

BackgroundThe recent molecular epidemiological studies concerning epidemiological studies concerning methicillin-resistant Staphylococcus aureus (MRSA) blood isolates from adult patients and susceptibilities of MRSA isolates with high vancomycin minimum inhibitory concentrations (MICs) (≥2mg/L) to linezolid, tigecycline, and daptomycin in Taiwan remain limited. The objectives of the study were (1) to better understand the change of molecular epidemiology of MRSA blood isolates and (2) to evaluate the in vitro activity of new anti-Gram-positive agents, including linezolid, tigecycline, and daptomycin.MethodsA total of 470 nonduplicate MRSA blood isolates from adult patients (older than 18 years) were collected from January 2006 to December 2008. The MICs of these isolates to various antibiotics were determined. Multilocus sequence typing was also performed in all isolates.ResultsThree sequence types (STs) constitute most (92.1%) of these 470 MRSA isolates: ST239 (53.2%), ST59 (23.2%), and ST5 (15.7%). Throughout the 3-year study, the ST239 strain remained predominant but with a significant trend of declining annually (p=0.03). In contrast, the proportion of isolates of ST59 increased, although the increment was insignificant (p=0.14). The proportion of MRSA isolates with a vancomycin MIC of 2mg/L was 17.2%. All of these isolates with a vancomycin MIC of 2mg/L were susceptible to linezolid and tigecycline, whereas most of them (98.8%) were susceptible to daptomycin.ConclusionsST239 remained predominant during the 3-year period but with a significant trend of declining. Moreover, linezolid, tigecycline, and daptomycin remained highly active against MRSA blood isolates, even with a vancomycin MIC of 2mg/L

Staphylococcal Cassette Chromosome mec in MRSA, Taiwan

To determine the predominant staphylococcal cassette chromosome (SCC) mec element in methicillin-resistant Staphylococcus aureus, we typed 190 isolates from a hospital in Taiwan. We found a shift from type IV to type III SCCmec element during 1992–2003, perhaps caused by selective pressure from indiscriminate use of antimicrobial drugs

Distribution of Staphylococcal Cassette Chromosome mec Types and Correlation with Comorbidity and Infection Type in Patients with MRSA Bacteremia

BACKGROUND: Molecular epidemiological definitions that are based on staphylococcal cassette chromosome mec (SCCmec) typing and phylogenetic analysis of methicillin-resistant Staphylococcus aureus (MRSA) isolates are considered a reliable way to distinguish between healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA). However, there is little information regarding the clinical features and outcomes of bacteremia patients with MRSA carrying different SCCmec types. METHODS: From January 1 through December 31, 2006, we recorded the demographic data and outcomes of 159 consecutive adult MRSA bacteremia patients from whom isolates for SCCmec analysis were collected. All participants were patients at a tertiary care center in Taiwan. PRINCIPAL FINDINGS: The following SCCmec types were identified in MRSA isolates: 30 SCCmec II (18.9%), 87 SCCmec III (54.7%), 22 SCCmec IV (13.8%), and 20 SCCmec V (12.6%). The time from admission to the first MRSA-positive blood culture for patients infected with isolates with the SCCmec III element (mean/median, 50.7/26 days) was significantly longer than for patients infected with isolates carrying SCCmec IV or V (mean/median, 6.7/3 days for SCCmec IV; 11.1/10.5 days for SCCmec V) (P<0.05). In univariate analysis, community onset, soft tissue infection, and deep-seated infection were predictors for SCCmec IV/V. In multivariate analysis, length of stay before index culture, diabetes mellitus, and being bedridden were independent risk factors associated with SCCmec II/III. CONCLUSIONS: These findings are in agreement with previous studies of the genetic characteristics of CA-MRSA. MRSA bacteremia with SCCmec II/III isolates occurred more among patients with serious comorbidities and prolonged hospitalization. Community onset, skin and soft tissue infection, and deep-seated infection best predicted SCCmec IV/V MRSA bacteremia