ceftazidime and Gram-Negative-Bacterial-Infections

In phase 3 clinical trials for ceftobiprole treatment of complicated skin and skin structure infections, 1,219 gram-positive and 276 gram-negative aerobic baseline pathogens were identified. Ceftobiprole inhibited all staphylococcal isolates, including methicillin-resistant strains, at MICs of

Topics: Anti-Bacterial Agents; Cephalosporins; Enterobacteriaceae; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Skin Diseases, Bacterial; Staphylococcus

The Capnocytophaga sputigena isolate NOR, responsible for septicemia, was resistant to amoxicillin and narrow-spectrum cephalosporins. In a cloning experiment, a new gene, bla(CSP-1), was identified; this gene encodes a novel extended-spectrum beta-lactamase (ESBL) that shares only 52% and 49% identities with the CME-1 and VEB-1 beta-lactamases, respectively. The G+C content of this gene, its genetic environment, the absence of conjugation transfer, and its detection in two reference strains suggested that it was an intrinsic resistance gene located on the chromosome.

Topics: Amino Acid Sequence; Amoxicillin; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Capnocytophaga; Cephalosporins; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Sepsis

Of 3,004 gram-negative bacilli collected from intra-abdominal infections in the Asia-Pacific region during 2007, 42.2% and 35.8% of Escherichia coli and Klebsiella spp., respectively, were extended-spectrum beta-lactamase (ESBL) positive. Moreover ESBL rates in India for E. coli, Klebsiella pneumoniae, and Klebsiella oxytoca were 79.0%, 69.4%, and 100%, respectively. ESBL-positive E. coli rates were also relatively high in China (55.0%) and Thailand (50.8%). Ertapenem and imipenem were the most active drugs tested, inhibiting over 90% of all species, including ESBL-positive isolates with the exception of Pseudomonas aeruginosa isolates (<90% susceptible to all study drugs) and ESBL-positive Klebsiella pneumoniae isolates (<90% susceptible to all study drugs except imipenem). Quinolones achieved 90% inhibition levels only against ESBL-negative K. pneumoniae and ESBL-negative K. oxytoca. A decline in ampicillin-sulbactam activity was noted, with only 34.5% of all Enterobacteriaceae inhibited in this study.

Topics: Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; China; Drug Resistance, Bacterial; Ertapenem; Escherichia coli; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Imipenem; India; Klebsiella; Quinolones; Thailand

Brachyspira pilosicoli BM4442, isolated from the feces of a patient with diarrhea at the Hospital Saint-Michel in Paris, was resistant to oxacillin (MIC > 256 microg/ml) but remained susceptible to cephalosporins and to the combination of amoxicillin and clavulanic acid. Cloning and sequencing of the corresponding resistance determinant revealed a coding sequence of 807 bp encoding a new class D beta-lactamase named OXA-63. The bla OXA-63 gene was chromosomally located and not part of a transposon or of an integron. OXA-63 shared 54% identity with FUS-1 (OXA-85), an oxacillinase from Fusobacterium nucleatum subsp. polymorphum, and 25 to 44% identity with other class D beta-lactamases (DBLs) and contained all the conserved structural motifs of DBLs. Escherichia coli carrying the bla OXA-63 gene exhibited resistance to benzylpenicillin and amoxicillin but remained susceptible to amoxicillin in combination with clavulanic acid. Mature OXA-63 consisted of a 31.5-kDa polypeptide and appeared to be dimeric. Kinetic analysis revealed that OXA-63 exhibited a narrow substrate profile, hydrolyzing oxacillin, benzylpenicillin, and ampicillin with catalytic efficiencies of 980, 250, and 150 mM(-1) s(-1), respectively. The enzyme did not apparently interact with oxyimino-cephalosporins, imipenem, or aztreonam. Unlike FUS-1 and other DBLs, OXA-63 was strongly inhibited by clavulanic acid (50% inhibitory concentration [IC50] of 2 microM) and tazobactam (IC50 of 0.16 microM) and exhibited low susceptibility to NaCl (IC50 of >2 M). OXA-63 is the first DBL described for the anaerobic spirochete B. pilosicoli.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Base Sequence; beta-Lactamases; Brachyspira; Cloning, Molecular; Diarrhea; Feces; Gram-Negative Bacterial Infections; Humans; Kinetics; Molecular Sequence Data; Oxacillin; Penicillin Resistance; Sequence Analysis, DNA

Doripenem, a 1beta-methylcarbapenem, is a broad-spectrum antibiotic approved for the treatment of complicated urinary tract and complicated intra-abdominal infections. An indication for hospital-acquired pneumonia including ventilator-associated pneumonia is pending. The current study examined the activity of doripenem against recent clinical isolates for the purposes of its ongoing clinical development and future longitudinal analysis. Doripenem and comparators were tested against 12,581 U.S. clinical isolates collected between 2005 and 2006 including isolates of Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pneumoniae, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. MICs (microg/ml) were established by broth microdilution. By MIC(90), doripenem was comparable to imipenem and meropenem in activity against S. aureus (methicillin susceptible, 0.06; resistant, 8) and S. pneumoniae (penicillin susceptible, < or =0.015; resistant, 1). Against ceftazidime-susceptible Enterobacteriaceae, the MIC(90) of doripenem (0.12) was comparable to that of meropenem (0.12) and superior to that of imipenem (2), though susceptibility of isolates exceeded 99% for all evaluated carbapenems. The activity of doripenem was not notably altered against ceftazidime-nonsusceptible or extended-spectrum beta-lactamase screen-positive Enterobacteriaceae. Doripenem was the most potent carbapenem tested against P. aeruginosa (MIC(90)/% susceptibility [%S]: ceftazidime susceptible = 2/92%S, nonsusceptible = 16/61%S; imipenem susceptible = 1/98.5%S, nonsusceptible = 8/56%S). Against imipenem-susceptible Acinetobacter spp., doripenem (MIC(90) = 2, 89.1%S) was twice as active by MIC(90) as were imipenem and meropenem. Overall, doripenem potency was comparable to those of meropenem and imipenem against gram-positive cocci and doripenem was equal or superior in activity to meropenem and imipenem against Enterobacteriaceae, including beta-lactam-nonsusceptible isolates. Doripenem was the most active carbapenem tested against P. aeruginosa regardless of beta-lactam resistance.

Topics: Anti-Bacterial Agents; Carbapenems; Doripenem; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Microbial Sensitivity Tests; United States

Metallo-beta-lactamases (MBLs) can confer resistance to most beta-lactams, including carbapenems. Their emergence in gram-negative pathogens is a matter of major concern. Italy was the first European country to report the presence of acquired MBLs in gram-negative pathogens and is one of the countries where MBL producers have been detected repeatedly. Here, we present the results of the first Italian nationwide survey of acquired MBLs in gram-negative pathogens. Of 14,812 consecutive nonreplicate clinical isolates (12,245 Enterobacteriaceae isolates and 2,567 gram-negative nonfermenters) screened for reduced carbapenem susceptibility during a 4-month period (September to December 2004), 30 isolates (28 Pseudomonas aeruginosa isolates, 1 Pseudomonas putida isolate, and 1 Enterobacter cloacae isolate) carried acquired MBL determinants. MBL producers were detected in 10 of 12 cities, with a predominance of VIM-type enzymes over IMP-type enzymes (4:1). Although having an overall low prevalence (1.3%) and significant geographical differences, MBL-producing P. aeruginosa strains appeared to be widespread in Italy, with a notable diversity of clones, enzymes, and integrons carrying MBL gene cassettes.

Topics: Base Sequence; beta-Lactam Resistance; beta-Lactamases; Data Collection; DNA Primers; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Integrons; Italy; Molecular Epidemiology; Molecular Sequence Data