RESUMEN
BACKGROUND: Improvements in blood culture techniques and molecular-based diagnostics have led to increased recognition of Kingella kingae as an invasive human pathogen causing bacteremia, septic arthritis, osteomyelitis and endocarditis in young children. Serious disease and potentially life-threatening complications of infection due to K. kingae necessitate timely identification and appropriate antimicrobial therapy. Ceftaroline is a fifth-generation broad spectrum cephalosporin that possesses activity against Gram-negative and Gram-positive pathogens similar to third-generation cephalosporins, but also includes methicillin-resistant Staphylococcus aureus . This study reports the in vitro activity of ceftaroline and comparator agents against an international collection of K. kingae isolates. METHODS: A collection of 308 K. kingae isolates was obtained primarily from children with bacteremia, endocarditis, osteoarticular infections or from asymptomatic pediatric carriers. Isolates were tested for antibiotic susceptibility using Clinical and Laboratory Standard Institute broth microdilution methodology and screened for ß-lactamase production using a nitrocefin chromogenic test. RESULTS: Ceftaroline inhibited all K. kingae isolates at ≤0.06 mg/L (MIC 50/90 , 0.015/0.03 mg/L). Ceftaroline MICs were similar to results with ceftriaxone (MIC 50/90 , 0.015/0.015 mg/L), meropenem (MIC 50/90 , 0.015/0.015 mg/L) and ampicillin-sulbactam (MIC 50/90 , 0.06/0.06 mg/L). Ceftaroline MICs were slightly lower than MICs for cefuroxime and amoxicillin/clavulanate (MIC 50/90 , 0.06/0.12 mg/L). MICs were high for clindamycin (MIC 50/90 , 2/4 mg/L) and oxacillin (MIC 50/90 , 4/8 mg/L). Sixteen isolates (5.2%) yielded a positive nitrocefin test indicating production of ß-lactamase; ceftaroline demonstrated equivalent MICs against ß-lactamase - positive and ß-lactamase - negative strains (MIC 50/90 , 0.015/0.3 mg/L). CONCLUSIONS: The potent activity of ceftaroline against this large international collection of K. kingae isolates supports further clinical evaluation in children.
Asunto(s)
Bacteriemia , Endocarditis , Kingella kingae , Staphylococcus aureus Resistente a Meticilina , Humanos , Niño , Preescolar , Antibacterianos/farmacología , Cefalosporinas/farmacología , beta-Lactamasas , Pruebas de Sensibilidad Microbiana , CeftarolinaRESUMEN
Surfactants might impact treatment of lower respiratory tract infections. Moreover, other body fluids, such as urine or serum, could impact antibacterial activity as well. Therefore, the impact of surfactants, urine, and serum on the antibacterial activity of the novel ß-lactam/ß-lactamase inhibitor combination of cefepime-enmetazobactam (FPE) was determined. Ten clinical isolates of Klebsiella pneumoniae, and the quality control strains K. pneumoniae ATCC 700603 and Escherichia coli NCTC 13353, were tested. Minimal Inhibitory Concentration (MIC) determinations (all strains) and Time Kill Curves (TKC) (one clinical isolate) were determined for FPE and piperacillin-tazobactam (TZP) with and without surfactant formulations Survanta® (SUR; 1%v/v) and Curosurf® (CUR; 1 mg ml-1). Determination of daptomycin MIC against Staphylococcus aureus ATCC 29213 in the presence and absence of surfactants was used as a positive control. Additionally, the impact of growth media supplemented with pooled human urine or serum were also evaluated by MIC testing. Expectedly, media supplemented with SUR increased the daptomycin MIC against S. aureus ATCC 29213. In contrast, the surfactants had no impact on the antibacterial activity of FPE against the tested Enterobacterales isolates. TKC experiments also revealed no impact of CUR on the antibacterial activity of FPE. These results demonstrate that the antibacterial activity of FPE is unaffected in the presence of lung surfactant. Moreover, FPE was not impacted by media supplemented with urine or serum.
Asunto(s)
Líquidos Corporales , Daptomicina , Humanos , Cefepima/farmacología , Inhibidores de beta-Lactamasas , Klebsiella pneumoniae , Cefalosporinas/farmacología , Tensoactivos , Staphylococcus aureus , Antibacterianos/farmacología , Monobactamas , Escherichia coli , Pruebas de Sensibilidad Microbiana , beta-LactamasasRESUMEN
Doripenem (formerly S-4661), a parenteral carbapenem, was tested in combination with an aminoglycoside (gentamicin) to determine the resistance selection of these codrugs during subinhibitory passaging using 6 Pseudomonas aeruginosa isolates. The organisms were selected based on doripenem and gentamicin MIC values to include isolates with MIC values near the susceptible breakpoints of both compounds and 1 strain highly resistant to gentamicin. Baseline MIC values were established for doripenem (2-8 microg/mL) and gentamicin (4 to >256 microg/mL) using reference broth microdilution methods, and passaging was carried out over 7 consecutive days. Doripenem MIC values increased 2 to >/=8-fold in 4 isolates, whereas 2 strains maintained the baseline doripenem MIC. When the experiment was performed with doripenem plus gentamicin, 3 strains maintained the original doripenem MIC values, 2 strains had a 2-fold increase, and only 1 strain showed a 4-fold increase in the doripenem MIC values. Previous studies have demonstrated doripenem to be more potent than other members in its class when tested against P. aeruginosa. The combination of doripenem and an aminoglycoside may be an effective treatment of infections caused by P. aeruginosa with elevated carbapenem MIC values with lower risk of selecting further resistance.
Asunto(s)
Aminoglicósidos/farmacología , Carbapenémicos/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Resistencia betalactámica/efectos de los fármacos , Doripenem , Interacciones Farmacológicas , Gentamicinas/farmacología , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Resistencia betalactámica/fisiología , beta-Lactamas/farmacologíaRESUMEN
Doripenem (formerly S-4661), a new 1-beta-methyl carbapenem, was challenged with a worldwide collection of 394 drug-refractory isolates. For endemic extended-spectrum beta-lactamase- and stably derepressed AmpC-producing enteric bacilli, the doripenem MICs at which 90% of the isolates were inhibited (MIC90s) were 0.03 to 0.5 microg/ml, generally lower than those of comparator carbapenems. A greater proportion of strains among carbapenem-resistant nonfermentative gram-negative bacilli were inhibited by doripenem at < or =4 microg/ml, and doripenem was the most active carbapenem (MIC90, 1 to 4 microg/ml) against penicillin-resistant streptococci.
Asunto(s)
Bacterias/efectos de los fármacos , Infecciones Bacterianas/microbiología , Carbapenémicos/farmacología , Bacterias/genética , Doripenem , Farmacorresistencia Bacteriana , Genotipo , Bacterias Gramnegativas/efectos de los fármacos , Humanos , FenotipoRESUMEN
OBJECTIVES: To investigate the potency of doripenem, a broad-spectrum carbapenem characterized by a wider spectrum of activity combining antimicrobial and bactericidal features of imipenem and meropenem. METHODS: This parenteral compound was studied against recent clinical isolates (2001-2002) from a worldwide organism collection. A total of 902 strains were susceptibility tested by reference methods against doripenem and six to 28 comparators including ertapenem, imipenem and meropenem. The organisms tested included: Enterobacteriaceae (281 strains), Acinetobacter spp. (33), Pseudomonas aeruginosa (35), Stenotrophomonas maltophilia (36), other non-fermenters (22), Haemophilus influenzae (61), Moraxella catarrhalis (33), oxacillin-susceptible staphylococci (39), enterococci (84), streptococci (163), various anaerobes (98), and other Gram-positive species such as Corynebacterium and Bacillus spp. (17). RESULTS: Against Enterobacteriaceae, the average doripenem MIC90 was 0.03 mg/L (range, < or =0.015-0.25 mg/L). Doripenem was two- to 16-fold more potent than imipenem and comparable to ertapenem and meropenem; all doripenem MIC values with enteric bacilli were < or =4 mg/L. Doripenem was active against Aeromonas (MIC50, 0.03 mg/L), Bacillus spp. (MIC50, 0.03 mg/L) and all tested anaerobic species (MIC range, < or =0.015-4 mg/L), but was less active against S. maltophilia (MIC90, >32 mg/L) and Enterococcus faecium (MIC90, >32 mg/L) among the enterococcal species. Time-dependent bactericidal action was observed for doripenem and broth MIC results were slightly greater when compared to agar MIC results. In pilot testing, the optimal doripenem disc concentration was 10 microg, identical to standardized reagents for other clinically available carbapenems. CONCLUSIONS: Doripenem appears to be a potent carbapenem with a spectrum resembling currently marketed antipseudomonal carbapenems, but with greater activity when tested against some non-fermentative bacillary strains. Continued evaluation of doripenem against isolates resistant to other beta-lactams appears to be warranted.
Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Infecciones Bacterianas/microbiología , Carbapenémicos/farmacología , Medios de Cultivo , Doripenem , Enterobacteriaceae/efectos de los fármacos , Enterococcus/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Control de Calidad , Infecciones del Sistema Respiratorio/microbiologíaRESUMEN
Aztreonam has been commonly used in various combinations to enhance antimicrobial spectrum of co-drugs and produce potential synergistic activity. Although well studied in vitro over 10 years ago, aztreonam combination testing has been poorly documented with newer or commonly used agents against contemporary isolates. All MIC tests (alone or in combination) used in this experiment were reference broth microdilution methods in checkerboard tray designs. Aztreonam was combined with ciprofloxacin, gatifloxacin, levofloxacin, cefepime, ceftazidime and imipenem at clinically relevant concentrations. Interaction categories were defined by established criteria. Forty strains each of Pseudomonas aeruginosa and Enterobacteriaceae (12 species; aztreonam MIC, 1-16 microg/ml) were tested for each antimicrobial combination (480 total determinations). No antagonism or indeterminate interactions were identified. The overall rates of synergy or partial synergy for aztreonam with fluoroquinolone combinations was 63.4% versus P. aeruginosa, greatest for aztreonam with gatifloxacin (67.5%). Interaction categories varied greatly among aztreonam with beta-lactam combinations. Aztreonam with ceftazidime or cefepime versus P. aeruginosa had 75.0 - 85.0% partial or complete synergy rates, but aztreonam with imipenem showed dominant indifference (65.0%). In contrast, aztreonam with imipenem was more likely to exhibit synergy (32.5%) when tested against Enterobacteriaceae. Aztreonam, often used as an aminoglycoside substitute in antimicrobial combinations, continues to demonstrate enhanced, but variable drug activity interactions for contemporary antimicrobial combinations when tested against recent (2002) clinical isolates.