Epidemiology and antimicrobial susceptibility of Gram-negative aerobic bacteria causing intra-abdominal infections during 2010-2011.

The study for monitoring antimicrobial resistance trends (SMART) surveillance program monitors the epidemiology and trends in antibiotic resistance of intra-abdominal pathogens to currently used therapies. The current report describes such trends during 2010-2011. A total of 25,746 Gram-negative clinical isolates from intra-abdominal infections were collected and classified as hospital-associated (HA) if the hospital length of stay (LOS) at the time of specimen collection was ≥48 hours, community-associated (CA) if LOS at the time of specimen collection was <48 hours, or unknown (no designation given by participating centre). A total of 92 different species were collected of which the most common was Escherichia coli: 39% of all isolates in North America to 55% in Africa. Klebsiella pneumoniae was the second most common pathogen: 11% of all isolates from Europe to 19% of all isolates from Asia. Isolates were from multiple intra-abdominal sources of which 32% were peritoneal fluid, 20% were intra-abdominal abscesses, and 16.5% were gall bladder infections. Isolates were further classified as HA (55% of all isolates), CA (39% of all isolates), or unknown (6% of all isolates). The most active antibiotics tested were imipenem, ertapenem, amikacin, and piperacillin-tazobactam. Resistance rates to all other antibiotics tested were high. Considering the current data set and high-level resistance of intra-abdominal pathogens to various antibiotics, further monitoring of the epidemiology of intra-abdominal infections and their susceptibility to antibiotics through SMART is warranted.

Activity of JNJ-Q2, a new fluoroquinolone, tested against contemporary pathogens isolated from patients with community-acquired bacterial pneumonia.

JNJ-Q2 is a broad-spectrum fluoroquinolone with bactericidal activity against Gram-positive and Gram-negative pathogens and is currently in clinical development for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin-structure infections. This study determined the activity of JNJ-Q2 against a worldwide year 2010 collection (89 centres in 27 countries) of three common respiratory pathogens (3757 isolates) from patients with CABP. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were tested by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method, and susceptibility rates for comparators were assessed using CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria. JNJ-Q2 had activity against all three species, with 96.9% of strains inhibited at ≤0.015 mg/L. JNJ-Q2 [minimum inhibitory concentration for 50% and 90% of the organisms, respectively (MIC(50/90))=0.008/0.015 mg/L] demonstrated a 16-fold greater potency compared with moxifloxacin (MIC(50/90)=0.12/0.25 mg/L) and at least 128-fold greater activity compared with levofloxacin (MIC(50/90)=1/ 1 mg/L) and ciprofloxacin (MIC(50/90)=1/2 mg/L) against S. pneumoniae. Haemophilus influenzae isolates were 21.9-23.3% resistant to ampicillin, but JNJ-Q2 (MIC(50/90)≤0.004/0.015 mg/L) was at least two-fold more active than moxifloxacin (MIC(50/90)=0.015/0.03 mg/L) as well as being potent against M. catarrhalis (MIC(90)=0.015/0.015 mg/L). In conclusion, JNJ-Q2 demonstrated increased potency compared with other marketed fluoroquinolones that have been used to treat CABP pathogens, thus favouring further clinical development.

In vitro evaluation of BAL9141, a novel parenteral cephalosporin active against oxacillin-resistant staphylococci.

Community-acquired and nosocomial infections caused by multidrug-resistant Gram-positive pathogens continue to increase in prevalence and have become a serious problem in many parts of the world. BAL9141 is a member of the class of parenteral pyrrolidinone-3-ylidenemethyl cephalosporins, and has a broad spectrum of activity. In the current study, BAL9141 was tested against a large number (n = 2263) of recent isolates from various international surveillance programmes including 1097 Gram-positive strains. Susceptibility to (S) and activity of (mg/L) to BAL9141, based on proposed breakpoints (MIC50/MIC90/% S) were as follows: methicillin-susceptible Staphylococcus aureus (0.5/0.5/100%), methicillin-resistant S. aureus (MRSA) (1/2/100%), methicillin-susceptible coagulase-negative staphylococci (CoNS) (0.12/0.25/100%), methicillin-resistant CoNS (MR-CoNS) (1/2/100%), Streptococcus pneumoniae (< or = 0.015/0.25/100%), viridans group streptococci (0.03/0.5/99%), beta-haemolytic streptococci (< or = 0.015/< or = 0.015/100%), Enterococcus faecalis (0.5/16/90%), Enterococcus faecium (>32/>32/22%), Haemophilus influenzae (0.06/0.06/100%), Moraxella catarrhalis (0.06/0.5/100%), Neisseria gonorrhoeae (0.03/0.06/100%) and Neisseria meningitidis (< or = 0.002/0.004/100%). BAL9141 susceptibility at < pr = 4 mg/L (100% S) surpassed that of ceftriaxone (CRO; 1% S) and quinupristin/dalfopristin (Q-D; 92% S) against MRSA and MR-CoNS (CRO 0.9% S; Q-D 94% S). All S. pneumoniae were inhibited by BAL9141 at < or = 1 mg/L compared with CRO (90% S) and levofloxacin (LVX; 98% S). Susceptibility rates for viridans group streptococci to BAL9141 (>98%) were also higher than to CRO (86%) and LVX (96%). BAL9141 demonstrated excellent activity against most species of wild-type enteric bacilli, with > or = 95% of isolates being susceptible; however, only modest activity was observed for BAL9141 against non-fermentative Gram-negative species and ESBL-producing Escherichia coli or Klebsiella pneumoniae. BAL9141 demonstrated excellent activity against many tested pathogens displaying various resistance phenotypes, and should be particularly valuable in the treatment of MRSA as well as for drug-resistant streptococci, while maintaining a spectrum resembling a 'third-generation' cephalosporin against other clinically important species.

In vitro evaluation of AZD2563, a new oxazolidinone, tested against beta-haemolytic and viridans group streptococci.

Linezolid was the first clinically applied agent from the oxazolidinone class, and AZD2563, a new agent, is described here. Five hundred and twenty-five streptococcal isolates were tested, including beta-haemolytic (266) and viridans group (259) species. MIC(50)/MIC(90)/% susceptible (susceptibility breakpoint <2 mg/L of AZD2563) results were, for beta-haemolytic species: AZD2563 (1/2/100), linezolid (1/2/100), quinupristin-dalfopristin (0.25/0.25/100), vancomycin (0.25/0.5/100) and levofloxacin (0.5/1/99); for viridans group species: AZD2563 (0.5/1/100), linezolid (1/1/100), quinupristin-dalfopristin (0.5/1/99), vancomycin (0.5/0.5/100) and levofloxacin (1/1/98). The modal MICs of AZD2563 and linezolid were 0.5 or 1 mg/L and 1 mg/L, respectively. AZD2563 activity screening against these non-pneumococcal streptococci indicated a slightly greater potency of AZD2563 when compared with linezolid. All AZD2563 MICs were <2 mg/L.

Linezolid-resistant Enterococcus faecium isolated from a patient without prior exposure to an oxazolidinone: report from the SENTRY Antimicrobial Surveillance Program.

A patient case report describes an Enterococcus faecium strain isolated from a blood culture that was resistant to linezolid (MIC, 8 microg/mL; G2576U mutation of 23S rRNA). Co-resistances were identified for vancomycin, ampicillin, macrolides, fluoroquinolones, chloramphenicol, rifampin, gentamicin (high-level), nitrofurantoin and trimethoprim/sulfamethoxazole. Etest (AB BIODISK, Solna, Sweden) and disk diffusion results also detected the oxazolidinone resistance pattern. Laboratories should be aware of the rare possibility of these strains occurring during linezolid therapy or spontaneously (this case) in contemporary practice, and have in vitro susceptibility methods available capable of detecting oxazolidinone resistance.