No abstract

Limited antimicrobials remain active for treating severe infections due to KPC-producing pathogens, and optimal regimens have not been established. In murine thigh infections caused by nine KPC-producing clinical strains of Enterobacteriaceae (meropenem MICs, 1 to 4 g/ml), we evaluated the activities of tigecycline, colistin, meropenem, rifampin, and gentamicin in single and combination regimens lasting for 24 h and 48 h. Rifampin, tigecycline, and gentamicin were the most effective monotherapies, reducing significantly the CFU counts yielded from thighs infected by 88.9 to 100%, 77.8 to 88.9%, and 66.7 to 88.9% of strains, respectively; meropenem and colistin alone exhibited considerably lower performance (significant CFU reduction in 33.3% and 22.2 to 33.3% of the strains, respectively). The addition of rifampin or gentamicin to tigecycline produced synergistic effect in most strains, while antagonism was observed in 33.3 to 44.4% of the strains when colistin was added to tigecycline and in 44.4 to 55.5% of the strains for meropenem combination with tigecycline. Tigecycline combinations with gentamicin or with rifampin caused higher CFU reductions than did tigecycline plus colistin or plus meropenem with almost all strains. Furthermore, tigecycline plus gentamicin was significantly more effective than tigecycline plus colistin or tigecycline plus meropenem in 33.3 to 44.4% and 55.5 to 66.7% of the strains, respectively, while tigecycline plus rifampin significantly outperformed tigecycline plus colistin and tigecycline plus meropenem in 33.3% and 66.7 to 77.8% of the strains, respectively. Overall, our in vivo study showed that tigecycline plus rifampin or plus gentamicin is a robust regimen against soft tissue infections caused by KPCproducing strains. The combinations of tigecycline with colistin or meropenem should be considered with caution in clinical practice.

Community-type Staphylococcus aureus strains that are positive for mecA and PBP2a but appear phenotypically susceptible to oxacillin are increasingly reported worldwide. Four S. aureus clinical isolates carrying the mecA gene with oxacillin MICs of <2 g/ml were tested for oxacillin efficiency by population analyses and experimental thigh infections. These isolates harbored staphylococcal cassette chromosome mec type IV and belonged to two genotypes. Two of the four isolates were found by population analysis to be truly oxacillin susceptible. All four isolates exhibited significant reductions in the numbers of colonies grown after dicloxacillin treatment of experimental thigh infections, as also did a mecA-negative S. aureus control strain. These observations indicate that some of the phenotypically oxacillin susceptible mecA-positive Staphylococcus aureus isolates may be at least partially responsive to oxacillin.

Much is known about microbes originally identified in caves, but little is known about the entrapment of microbes (bacteria) in stalactites and their possible environmental origins. This study presents data regarding the significant environmental distribution of prokaryotic bacterial taxa of a Greek stalactite core. We investigated the involvement of those bacteria communities in stalactites using a metataxonomic analysis approach of partial 16S rRNA genes. The metataxonomic analysis of stalactite core material revealed an exceptionally broad ecological spectrum of bacteria classified as members of Proteobacteria, Actinobacteria, Firmicutes, Verrucomicrobia, and other unclassified bacteria. We concluded that (i) the bacterial transport process is possible through water movement from the upper ground cave environment, forming cave speleothems such as stalactites, (ii) bacterial genera such as Polaromonas, Thioprofundum, and phylum Verrucomicrobia trapped inside the stalactite support the paleoecology, paleomicrobiology, and paleoclimate variations, (iii) the entrapment of certain bacteria taxa associated with water, soil, animals, and plants such as Micrococcales, Propionibacteriales, Acidimicrobiales, Pseudonocardiales, and α-, β-, and γ-Proteobacteria.

We compared the activity of dicloxacillin with that of vancomycin against 15 oxacillin-susceptible, methicillin-resistant Staphylococcus aureus (OS-MRSA) clinical isolates. By population analyses, we found that 6 OS-MRSA isolates were able to grow in the presence of up to 8 g/ml dicloxacillin and 9 isolates were able to grow in 12 to >32 g/ml dicloxacillin; all isolates grew in up to 2 g/ml vancomycin. Both drugs exhibited similar bactericidal activities. In experimental infections, the therapeutic efficacy of dicloxacillin was significant (P < 0.05 versus untreated controls) in 10 OS-MRSA isolates and vancomycin was effective (P < 0.05) against 12 isolates; dicloxacillin had an efficacy that was comparable to that of vancomycin (P > 0.05) in 8 isolates. The favorable response to dicloxacillin treatment might suggest that antistaphylococcal penicillins could be used against OS-MRSA infections. Staphylococcus aureus isolates that carry and express the mecA gene are considered methicillin resistant (MRSA) but may exhibit oxacillin MICs ranging from the susceptible range (Յ2 g/ ml) to Ͼ1,000 g/ml (8,16,20). It was generally believed that most mecA-positive S. aureus strains, including those appearing oxacillin susceptible (OS-MRSA), exhibit a degree of oxacillin heteroresistance and the use of ␤-lactams might lead to treatment failure. However, OS-MRSA isolates with no oxacillin heteroresistance (truly oxacillin susceptible) also appeared (9).In a previous study, we reported that the activity of oxacillin against four OS-MRSA isolates was intermediate between that against mecA-negative S. aureus and highly resistant MRSA isolates (9). It was subsequently found that the OS-MRSA isolates of that study harbored specific mutations in their Fem proteins that probably conferred atypical oxacillin responsiveness (6). To further investigate these preliminary observations, we tested and report herein the in vitro and in vivo activities of oxacillin compared with those of vancomycin (treatment of choice for most MRSA infections) against a larger collection of OS-MRSA. The aim of this study was to investigate whether antistaphylococcal ␤-lactams, which were previously shown to exhibit superior activity than vancomycin against methicillin-susceptible S. aureus (MSSA) (11), retain activity against MRSA isolates that appear phenotypically susceptible to oxacillin. To the best of our knowledge, the activity of ␤-lactams has not been tested against OS-MRSA isolates.Bacterial strains and susceptibility testing. Fifteen vancomycin-susceptible OS-MRSA clinical isolates, collected during 2006 and 2007, were studied. A high-level MRSA isolate (isolate 7263; oxacillin MIC, 256 g/ml) and the mecA-negative strain S. aureus ATCC 29213 were included as controls. Isolates were stored at Ϫ80°C in brain heart infusion broth with 15% glycerol before testing. MIC testing of oxacillin and vancomycin was performed by agar dilution according to CLSI guidelines (4).Detection of PBP2a and the mecA gene and MLST. The study isolates were tested for the...