kidney transplant recipients were diagnosed with adenovirus disease. The median time to infection was 5 (range, 2-300) weeks after transplantation. Of the 17 patients, 13 (76.5%) presented early, within 3 months posttransplant, and four (23.5%) presented late, more than 3 months after transplant. Besides urinary tract, involvement of other organs was common (63.6%) among patients with adenovirus viremia. Despite reduction of immunosuppression, six patients subsequently had a rise in the level of blood viral load, mostly within a week after diagnosis. However, only three (27.3%) patients with early infection developed disease progression. Compared to the late infection group, patients with early infection had significantly lower absolute lymphocyte counts at week 1 (p = 0.01) and 3 (p = 0.002) after diagnosis. Four patients received intravenous cidofovir. At 6-month follow-up, 10 (90.9%) patients had reversible graft dysfunction. Only one (5.7%) died from bacterial sepsis. Adenovirus disease is a significant complication following kidney transplantation. Early case recognition with reduction of immunosuppression is critical. Serial blood adenovirus viral loads and assessment of lymphocyte recovery are also useful in monitoring the course of infection.

The complete sequence (1,479 nucleotides) of msrC, part of which was recently reported by others using a different strain, was determined. This gene was found in 233 of 233 isolates of Enterococcus faecium but in none of 265 other enterococci. Disruption of msrC was associated with a two-to eightfold decrease in MICs of erythromycin azithromycin, tylosin, and quinupristin, suggesting that it may explain in part the apparent greater intrinsic resistance to macrolides of isolates of E. faecium relative to many streptococci. This endogenous, species-specific gene of E. faecium is 53% identical to msr(A), suggesting that it may be a remote progenitor of the acquired macrolide resistance gene found in some isolates of staphylococci.We have recently screened a number of gram-positive cocci for macrolide susceptibility (12) and subsequently for some of the acquired resistance genes, erm(A), erm(B), erm(C), ere(A), ere(B), mef(A), and msr(A) (24,29), that are known to effect macrolide, streptogramin, and/or lincosamide (MS/L) susceptibility (unpublished data). We noted that some of the Enterococcus faecium isolates for which the MICs (2 to 16 g/ml) of erythromycin (ERY) were elevated failed to hybridize to any of the aforementioned resistance gene probes. We next performed PCR amplification using DNA from macrolide nonsusceptible, probe-negative E. faecium strains and primers for msr(A/B) (29); a fragment with homology to msr(A) and msr(B), the acquired macrolide resistance genes found in staphylococci, was recovered. In the current work, the complete sequence (1,479 nucleotides [nt]) of the gene encompassing this fragment along with ϳ450 bp upstream was determined. This gene was found to contain the 405-bp fragment previously deposited in GenBank (accession no. AJ243209) and recently reported as msrC, a species-specific gene of E. faecium (22). An insertion disruption mutation of this gene has now been generated and the E. faecium mutant was found to be more susceptible to ERY, azithromycin, tylosin, and quinupristin, suggesting that this msr-like gene can confer some protection to isolates of E. faecium against these antimicrobials. MATERIALS AND METHODSBacterial strains and MIC studies. The microorganisms used in this study were obtained from the collection of our laboratory over the past several years. A total of 498 isolates of enterococci, 56 streptococcal isolates (some of which were previously described) (5, 12), and two staphylococcal isolates (as negative controls for the gene described) were used in the various studies. The majority of these clinical isolates came from the United States but some were from Thailand, Argentina, Belgium, and Spain. The enterococcal isolates included 246 Enterococcus faecalis, 233 E. faecium, 6 E. hirae, 5 E. durans, 2 E. casseliflavus, 2 E. mundtii, 2 Staphylococcus aureus, 1 E. gallinarum, 2 E. solitarius, and 1 E. raffinosus isolate. ERY MICs were also determined by agar dilution (19,20) for a group of 90 E. faecalis, 64 E. faecium, 29 Streptococcus pyogenes, 10 group B strept...

Population pharmacokinetics of vancomycin in Thai adult patients was determined by non-linear mixed-effects approach using 319 vancomycin serum concentrations from 212 patients. The data were best fitted by a two-compartment model and it was used to examine the effect of patient characteristics on the vancomycin pharmacokinetics. In the final model, there was a linear relationship between vancomycin clearance, CL (L/h), and creatinine clearance calculated by Cockcroft-Gault equation, CLCr (mL/min): CL  =0.044  ×  CLCr. Meanwhile, volume of central compartment, V 1 (L), was linearly related with the age (years old): V 1 = 0.542  × Age. Intercompartment clearance (Q) and volume of peripheral compartment (V 2) was 6.95 L/h and 44.2 L, respectively. The interindividual variability for CL, V 1, Q, and V 2 was 35.78, 20.93, 39.50, and 57.27%, respectively. Whereas, the intraindividual variability was 4.51 mg/L. Final model then was applied to predict serum vancomycin concentrations on validation group. Predictive performance revealed a bias of −1.43 mg/L (95% CI: −5.82–2.99) and a precision of 12.2 mg/L (95% CI: −1.60–26.16). In conclusion, population pharmacokinetic of vancomycin in Thai adult patients was developed. The model could be used to create vancomycin dosage regimen in the type of patient similar with the present study.

We tested 165 enterococcal isolates, biased toward vancomycin resistant (VR) isolates, collected during recent years from fecal samples of healthy subjects and clinical specimens of hospitalized patients (mostly from United States and some from Europe) for susceptibility to 19 antimicrobials. Nosocomial isolates, whether VR or not, were more often highly resistant to aminoglycosides and clindamycin than fecal isolates from healthy community volunteers and more often resistant to erythromycin, chloramphenicol, trimethoprim, levofloxacin and, for E. faecium, ampicillin (93 vs. 0%). Resistance rates were similar between nosocomial and community-fecal isolates for minocycline, rifampin and quinupristin-dalfopristin (Q-D). None of the 165 enterococci tested hybridized with aph(2'')-Ic and aph(2'')-Id probes for recently described gentamicin resistance genes and 37 of the 39 isolates with high level resistance (HLR) to gentamicin hybridized with an intragenic aac(6')-aph(2'') probe. Of the two newer drugs tested, daptomycin MIC90s were 0.25 microg/mL for E. faecalis and 1 microg/mL for E. faecium, regardless of their vancomycin resistance level or source. For Q-D, none of 28 E. faecium from community based healthy subjects in the USA and 7 of 66 E. faecium from hospitalized patients in the United States were resistant. Among these 7 Q-Dr United States isolates and 7 Q-Dr isolates from Europe (MICs of Q-D of 4-8 microg/mL), none hybridized with vat(D) (formerly satA) and vat(E) (formerly satG) DNA probes, indicating the involvement of other mechanism/s of resistance in these isolates. We also demonstrated that an intragenic probe of the gene ace from E. faecalis showed specific hybridizations to all E. faecalis isolates, suggesting the usefulness of this gene for identification of this species.