Antibiotic resistance is a public health problem with increasingly alarming data being reported. Gram-positive bacteria are among the protagonists of severe nosocomial and community infections. The ...objective of this review is to conduct an extensive examination of emerging treatments for Gram-positive infections including ceftobiprole, ceftaroline, dalbavancin, oritavancin, omadacycline, tedizolid, and delafloxacin. From a methodological standpoint, a comprehensive analysis on clinical trials, molecular structure, mechanism of action, microbiological targeting, clinical use, pharmacokinetic/pharmacodynamic features, and potential for therapeutic drug monitoring will be addressed. Each antibiotic paragraph is divided into specialized microbiological, clinical, and pharmacological sections, including detailed and appropriate tables. A better understanding of the latest promising advances in the field of therapeutic options could lead to the development of a better approach in managing antimicrobial therapy for multidrug-resistant Gram-positive pathogens, which increasingly needs to be better stratified and targeted.
The emergence of the plasmid-mediated colistin resistance mechanism in
has raised concern among public health experts as colistin is a last-line antimicrobial resort. The primary aim of the study was ...to investigate the prevalence of this resistance trait in
isolates circulating in the Lombardy region, Northern Italy. The presence of
-type genes and their genetic relationship were also studied.
A prospective study was performed during a 4-month period (May to August, 2016) in six acute care Hospitals. Consecutive nonduplicate clinical isolates of
from any type of clinical specimen, with the exception of rectal swabs, were included in the study. Isolates that exhibited MIC values for colistin >2 mg/L were further investigated. Bacterial identification was obtained by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Amplification of
-type genes (-1 to -5 variants) and microarray analysis were accomplished. Repetitive sequence-based PCR (Rep-PCR) and multilocus sequence typing (MLST) analysis were used for genotyping.
Overall, 3,902 consecutive
isolates (2,342 from outpatients, 1,560 from inpatients) were evaluated during the study period. Of them, 18/3,902 (0.5%), collected from 4/6 centers, showed resistance to colistin. These isolates were mostly obtained from urine of both outpatients (n=12) and inpatients (n=6). Colistin MIC values ranged from 4 to 8 mg/L. The
gene was detected in 10/18 isolates (7 from outpatients, 3 from inpatients). Rep-PCR and MLST analysis revealed the presence of nine different clusters. Further
-type genes were not detected.
Resistance to colistin in
clinical isolates appears low in our geographic area. With regard to
-positive isolates, they accounted for approximately 50% of colistin-resistant
isolates, thus representing a relevant resistance mechanism in this context. Although overall limited, the presence of
determinant in our region should not be ignored and great concern should be given to the continuous surveillance.
Yeasts are a common cause of invasive fungal infections in critically ill patients. Antifungal susceptibility testing results of clinically significant fungal strains are of interest to physicians, ...enabling them to adopt appropriate strategies for empiric and prophylactic therapies. We investigated the antifungal susceptibility of yeasts isolated over a 2-year period from hospitalised patients with invasive yeast infections.
638 yeasts were isolated from the blood, central venous catheters and sterile fluids of 578 patients on general and surgical intensive care units and surgical wards. Etest strips and Sensititre panels were used to test the susceptibility of the isolates to amphotericin B, anidulafungin, caspofungin, fluconazole, itraconazole, posaconazole and voriconazole in 13 laboratories centres (LC) and two co-ordinating centres (CC). The Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method was used at the CCs for comparison.
Etest and Sensititre (LC/CC) MIC90 values were, respectively: amphotericin B 0.5/0.38, 1/1 mg/L; anidulafungin 2/1.5 and 1/1 mg/L; caspofungin 1/0.75 and 0.5/0.5 mg/L; fluconazole 12/8 and 16/16 mg/L; itraconazole 1/1.5, 0.5/0.5 mg/L; posaconazole 0.5 mg/L and voriconazole 0.25 mg/L for all. The overall MIC90 values were influenced by the reduced susceptibility of Candida parapsilosis isolates to echinocandins and a reduced or lack of susceptibility of Candida glabrata and Candida krusei to azoles, in particular fluconazole and itraconazole. Comparison of the LC and CC results showed good Essential Agreement (90.3% for Etest and 92.9% for Sensititre), and even higher Categorical Agreement (93.9% for Etest and 96% for Sensititre); differences were observed according to the species, method, and antifungal drug. No cross-resistance between echinocandins and triazoles was detected.
Our data confirm the different antifungal susceptibility patterns among species, and highlight the need to perform antifungal susceptibility testing of clinically relevant yeasts. With the exception of a few species (e.g. C. glabrata for azoles and C. parapsilosis for echinocandins), the findings of our study suggest that two of the most widely used commercial methods (Etest and Sensititre) provide valid and reproducible results.
The Phoenix system (Becton Dickinson Diagnostic Systems, Sparks, MD) was evaluated for identification (ID) to the species level of streptococci and enterococci. Two hundred clinical isolates were ...investigated: beta-hemolytic streptococci (n = 50), Streptococcus pneumoniae organisms (n = 46), viridans group streptococci (n = 31), Enterococcus faecium (n = 36), Enterococcus faecalis (n = 25), and other catalase-negative cocci (n = 12). The API system (bioMérieux, Marcy l'Étoile, France) was used as a comparator. Molecular methods (sequencing of 16S rRNA and zwf and gki genes and ddl gene amplification) were used to investigate discordant results. Upon resolution of discrepancies, correct species ID was achieved by the Phoenix system for 121/129 (93.8%) streptococci and 63/70 (90.0%) enterococci. Excellent results were obtained for S. pneumoniae (45/45) and beta-hemolytic streptococci (49/50). With regard to viridans streptococci, the accuracy of the Phoenix system was 83.9%. Among the latter organisms, the best performance was obtained with isolates of the Streptococcus sanguinis group and Streptococcus anginosus group; problems were instead encountered with the Streptococcus mitis group. Four E. faecium and three E. faecalis isolates were misidentified as Enterococcus casseliflavus/Enterococcus gallinarum or Enterococcus durans. Thus, these isolates were identified only at the genus level. Compared with commercially available systems, the Phoenix system appears a reliable diagnostic tool for identifying clinically relevant streptococci and enterococci. The SMIC/ID-2 panel proved particularly effective for beta-hemolytic streptococci and pneumococci.
Drug resistance is an emerging problem among streptococcal and enterococcal species. Automated diagnostic systems for species identification and antimicrobial susceptibility testing (AST) have become ...recently available. We evaluated drug susceptibility of clinical isolates of streptococci and enterococci using the recent Phoenix system (BD, Sparks, MD). Diagnostic tools included the new SMIC/ID-2 panel for streptococci, and the PMIC/ID-14 for enterococci. Two-hundred and fifty isolates have been investigated: beta-hemolytic streptococci (n = 65), Streptococcus pneumoniae (n = 50), viridans group streptococci (n = 32), Enterococcus faecium (n = 40), Enterococcus faecalis (n = 43), other catalase-negative cocci (n = 20). When needed, species ID was determined using molecular methods. Test bacterial strains were chosen among those carrying clinically-relevant resistance determinants (penicillin, macrolides, fluoroquinolones, glycopeptides). AST results of the Phoenix system were compared to minimal inhibitory concentration (MIC) values measured by the Etest method (AB Biodisk, Solna, Sweden).
Streptococci: essential agreement (EA) and categorical agreement (CA) were 91.9% and 98.8%, respectively. Major (ME) and minor errors (mE) accounted for 0.1% and 1.1% of isolates, respectively. No very major errors (VME) were produced. Enterococci: EA was 97%, CA 96%. Small numbers of VME (0.9%), ME (1.4%) and mE (2.8%) were obtained. Overall, EA and CA rates for most drugs were above 90% for both genera. A few VME were found: a) teicoplanin and high-level streptomycin for E. faecalis, b) high-level gentamicin for E. faecium. The mean time to results (+/- SD) was 11.8 +/- 0.9 h, with minor differences between streptococci and enterococci.
The Phoenix system emerged as an effective tool for quantitative AST. Panels based on dilution tests provided rapid and accurate MIC values with regard to clinically-relevant streptococcal and enterococcal species.
The new "low-inoculum" mode of the Phoenix system was evaluated to identify clinical coagulase-negative staphylococci. API ID32 Staph panels were used as comparators, and discrepancies were resolved ...by 16S rRNA and tuf gene analysis. The system correctly identified 90.5% of isolates, with a mean time of 10.2 h. Accuracy was satisfactory for Staphylococcus epidermidis, S. saprophyticus, and S. haemolyticus.
We report on the first detection of 2 cases of invasive Haemophilus influenzae type a (Hia) disease in Italy. The cases were sustained by the same Hia "strain" belonging to the ST23 clone that has ...previously been reported only outside Europe. The emergence of invasive Hia disease is of concern.
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