Oxacillin-susceptible Staphylococci Research Articles

1260. In Vitro Activity of Eravacycline Against Clinically Significant Bacteria Isolated from Patients with Cancer

Abstract Background Bacterial infections are common in patients with cancer (PWC). Many bacteria have developed resistance to currently used antibiotics, posing therapeutic challenges. we evaluated the in vitro activity of eravacycline (a novel fluorocycline) against clinical bacteria recently (2018-2019) isolated from PWC. Methods All 565 isolates tested were from blood cultures. CLSI approved broth microdilution method was used. Appropriate ATCC controls were included. MIC50, MIC90, MIC ranges and percent susceptibility calculations were made using FDA breakpoints when available. Eravacycline susceptibility breakpoint for most Gram-positive organisms (GPO) is ≤ 0.06 mg/L and for Enterobacterales is ≤ 0.5 mg/L. Results Eravacycline had potent activity against Staphylococcus aureus (methicillin-susceptible and resistant strains), oxacillin-susceptible coagulase-negative staphylococci (CoNS) including Staphylococcus lugdunensis, viridans group streptococci, beta-hemolytic streptococci. Streptococcus pneumoniae. Bacillus spp., Corynebacterium spp., and Micrococcus spp. It was slightly less active against oxacillin-resistant CoNS, and vancomycin-susceptible Enterococcus faecalis (MIC90 0,125 mg/L respectively) and was moderately active against vancomycin-resistant Enterococcus faecium (MIC50, 0.06, and MIC90. 0.25 mg/L). Eravacycline had potent activity against Escherichia coli (including ESBL producing strains), Citrobacter spp., and non-ESBL Klebsiella spp. Eravacycline inhibited 83% of ESBL positive K. pneumoniae, 83% of Enterobacter cloacae, and 80% of carbapenem-resistant Enterobacteriaceae (CRE) isolates at ≤ 0.5 mg/L. The presence of ESBLs increased MIC90 value no more than 2 fold. Eravacycline was also active against many non-fermentative GNB (Achromobacter spp., Acinetobacter spp., Sphingomonas paucimobilis, and Stenotrophomonas maltophilia). Table 1. Percent Susceptibility of Gram-negative isolates to Eravacycline Table 2. Percent Susceptibility of Gram-positive isolates to Eravacycline Conclusion Our data demonstrate that eravacycline has promising activity against clinically significant bacterial pathogens isolated from PWC including many drug resistant strains such as CRE and non--fermentative GNB. it might play an important role in the treatment of bacterial infections in PWC and warrants clinical evolution in this setting. Disclosures Samuel L. Aitken, PharmD, MPH, BCIDP, Melinta Therapeutoics (Individual(s) Involved: Self): Consultant, Grant/Research Support Kenneth Rolston, MD, Tetraphase Pharmaceuticals (Grant/Research Support)

Identification of Variable Traits among the Methicillin Resistant and Sensitive Coagulase Negative Staphylococci in Milk Samples from Mastitic Cows in India.

Methicillin resistant Staphylococcus aureus causing bovine mastitis has been very well investigated worldwide. However, there are only limited reports on the characterization of methicillin resistant and sensitive coagulase negative staphylococci (CoNS) across the globe. Hence, in the present study, we aim to determine the phenotypic traits based on antimicrobial susceptibility profile and genotypic characterization by verifying the presence of resistance determinants, virulence and toxin genes present in the CoNS causing clinical mastitis. We obtained 62 CoNS isolates from 167 mastitic milk samples collected from three different states of India. The 62 isolates comprises of 10 different CoNS species S. sciuri, S. haemolyticus, S. chromogenes, S. saprophyticus, S. xylosus, S. simulans, S. agnetis, S. epidermidis, S. gallinarum, and S. cohinii. Susceptibility screening against 11 antibiotics determined 45.16% isolates as multidrug resistant (resistant to more than two class of antibiotic), 46.74% resistant (one or two antibiotic class) and 8.06% isolates were pan-sensitive (sensitive to all drugs). High resistance was observed against oxacillin and cefoxitin, whereas all isolates were susceptible toward vancomycin and linezolid. Fifty three isolates were methicillin resistant and 9 isolates were sensitive as determined by oxacillin susceptibility assay. The methicillin resistance gene, mecA was found in 95.16% isolates and staphylococcal cassette chromosome mec (SCCmec) typing predominantly revealed Type III (n = 34) and Type V (n = 18). Interestingly, 11.9% of mecA positive isolates were oxacillin susceptible and referred as oxacillin susceptible mecA positive staphylococci (OS-MRS). Additionally, genes encoding for enterotoxin, (sea, seb, seh, see) toxic shock syndrome (tsst), exfoliatin (eta, etb, etd) and virulence (pvl, Y-hlg) were also screened. Of all the genes examined, 67.74% of isolate were positive for the Y-hlg gene, followed by the sea gene in 25.8% whereas in none of the isolates the eta and the etb gene was amplified. The study also highlights the incidence of clinical isolates of CoNS, which are harboring the toxin and the virulence genes rendering them as a more potential threat. This is the first report of animal origin OS-MRS from India, which emphasizes on the inclusion of both the genetic and phenotypic test for proper characterization of CoNS and preventing resistant strain misidentification.

Chronic infection of unicompartmental knee arthroplasty: One-stage conversion to total knee arthroplasty

BackgroundThe main reasons for revision of unicompartmental knee arthroplasty (UKA) are loosening, wear, extension of osteoarthritis to another compartment, and infection. There have been no studies of the management of infected UKA, whose incidence varies from 0.2% to 1%. Our objective was to describe infection-related and mechanical outcomes of chronic UKA infection managed by one-stage conversion to total knee arthroplasty (TKA). Patients and methodsConsecutive patients with chronic UKA infection managed by one-stage conversion to TKA between January 2003 and December 2010 were included in a retrospective single-center study. All patients also received appropriate dual antibiotic therapy intravenously for 6weeks then orally for 6 additional weeks. ResultsDuring the study period, among 233 cases of infected knee arthroplasty managed at our center, 9 met the study inclusion criteria. The UKA was medial in 6 patients, lateral in 2, and patellofemoral in 1. Median age was 67years (range, 36–83years) and median infection duration was 9months. In 5 patients, previous treatment with synovectomy, joint lavage, and antibiotics had failed. The following bacteria were identified: oxacillin-susceptible Staphylococci, n=6 (S. epidermidis, n=4; S. capitis, n=1; and S. lugdunensis, n=1); nutritionally deficient Streptococcus, n=1; Enterococcus durans, n=1; and Escherichia coli, n=1. Median follow-up was 60months (range, 36–96months). No patient experienced recurrent infection or required revision surgery for infection. No medical complications limiting the use of appropriate antibiotic therapy were recorded. The mean preoperative knee and function scores were 60 and 50, respectively; corresponding mean postoperative values were 75 and 65, respectively. DiscussionUKA infection involves both the prosthesis and the native cartilage, neither of which can be treated conservatively in chronic forms. After identification of the causative organism, synovectomy and joint excision followed by same-stage TKA and combined with appropriate antibiotic therapy for 3months is effective. Level of evidenceIV, retrospective cohort study.

Re-evaluation of the Role of Broad-Spectrum Cephalosporins Against Staphylococci by Applying Contemporary In-Vitro Results and Pharmacokinetic- Pharmacodynamic Principles

The potency of cefepime, ceftriaxone, and ceftazidime was assessed by CLSI broth microdilution methods against 41,644 S. aureus (63.2% oxacillin-susceptible) and 14,266 coagulase-negative staphylococci (CoNS; 22.2% oxacillin-susceptible) through the SENTRY Antimicrobial Surveillance Program database (1998-2004). Using normal volunteer pharmacokinetic data and a linear intermittent intravenous infusion model, and an animal-derived pharmacokinetic/pharmacodynamic (PK-PD) target of ≥40% time above MIC, expected probabilities of target attainment (PTA) for cephems were evaluated using Monte Carlo simulation. Current CLSI breakpoints would rank the tested agents cefepime ≥ ceftriaxone > ceftazidime and by PK-PD PTA cefepime > ceftazidime > ceftriaxone. Cefepime has a potency advantage over ceftazidime (four- to eight-fold) and superiority at the usual dosing over ceftriaxone (22.7-66.1%) for oxacillin-susceptible staphylococci. Ceftazidime pharmacokinetic overcomes by-weight activity disadvantages, while a low proportion (<5%) of active free-drug penalizes ceftriaxone in the PTA calculations. PTA remained at ≥0.9 to a breakpoint of 8 mg/L for cefepime (1 g q8 or 12 hours) and ceftazidime and to a breakpoint of 2 mg/L for ceftriaxone. Regardless of applied breakpoint (CLSI or PKPD), cefepime has the widest and most potent anti-staphylococcal activity among commonly used “third- or fourth-generation” cephems. When used at doses ≥3 g/day, cefepime assures maximal coverage of oxacillin-susceptible staphylococci whether using existing (CLSI) or modified (PK-PD) breakpoints. Ceftriaxone should be used with caution.

Activity of Dalbavancin Tested against Staphylococcus spp. and β-Hemolytic Streptococcus spp. Isolated from 52 Geographically Diverse Medical Centers in the United States

Dalbavancin is a lipoglycopeptide antimicrobial agent with a potency significantly better than that of vancomycin when tested against staphylococci and streptococci. These two pathogens are common causes of skin and skin structure infections (SSSIs), and dalbavancin has been approved for the treatment of moderate to severe SSSIs. This study generated susceptibility data for staphylococci and beta-hemolytic streptococci from 52 U.S. medical centers that locally tested dalbavancin, vancomycin, and other antimicrobial class representatives to assess the potency of dalbavancin and the overall contemporary activities of commonly prescribed agents. Locally generated data showed that oxacillin-resistant staphylococci (57.0% overall) had slightly higher dalbavancin MIC(90) values (0.19 microg/ml) than oxacillin-susceptible strains (0.125 microg/ml). This potency was 8- to 16-fold greater than that for vancomycin. beta-Hemolytic streptococci had MIC(90) values ranging between <or=0.016 and 0.064 microg/ml (highest for group B isolates). Levofloxacin, gentamicin, and tetracycline were active against oxacillin-susceptible staphylococci (82 to 99% susceptible), with lower susceptibility rates seen for the oxacillin-resistant strains. Linezolid coverage was >98% against staphylococci. Erythromycin resistance was high for staphylococci (30.6 to 94.1%) with inducible clindamycin resistance rates of 26.0% and 55.0% for oxacillin-susceptible and -resistant Staphylococcus aureus, respectively. Beta-hemolytic streptococci had a 20.2% erythromycin resistance rate and a 60% inducible clindamycin resistance rate but were highly susceptible to other tested agents. Etest reading errors were apparent and skewed results towards slightly higher dalbavancin MICs, requiring further education on how to interpret Etest method results for this compound. Current disk diffusion breakpoint criteria for oxacillin susceptibility for S. aureus showed a very-major-error rate of 2.3% and only a 0.9% minor-error rate when cefoxitin was used to predict oxacillin susceptibility. Dalbavancin demonstrated excellent potency and activity (100% susceptibility at proposed breakpoints) against common causes of SSSI pathogens in this U.S. multicenter study sample.

The Meropenem Yearly Susceptibility Test Information Collection antimicrobial susceptibility program in Spain: a 5-year analysis

The Meropenem Yearly Susceptibility Test Information Collection program is a global study providing in vitro surveillance data on antimicrobial susceptibility in centers prescribing meropenem. This study summarizes data on the activity of meropenem and 5 comparators against 4022 clinical isolates from 7 centers in Spain (1999–2003). Those bacteria intrinsically resistant to meropenem were excluded. Among Enterobacteriaceae, 100% of Enterobacter spp., Citrobacter spp., and Serratia spp. were susceptible to meropenem. Escherichia coli and Klebsiella pneumoniae susceptibilities to carbapenems were 100% and ≥98%, respectively. Extended-spectrum β-lactamase–producing Enterobacteriaceae were 3.8% of isolates, and all of them were susceptible to meropenem. Ciprofloxacin resistance in E. coli was around 20%. Meropenem and piperacillin/tazobactam were the most active agents against Pseudomonas aeruginosa. Acinetobacter baumannii were 61–90% susceptible to carbapenems, but only 6–21% susceptible to ciprofloxacin. In this period, around 100% of oxacillin-susceptible staphylococci were susceptible to meropenem. There was no significant decrease in susceptibility to the carbapenems throughout the 5-year period. The clinical use of meropenem in 7 Spanish centers did not increase bacterial resistance to this agent in the microorganisms evaluated.

Contemporary activity of meropenem and comparator broad-spectrum agents: MYSTIC program report from the United States component (2005)

The Meropenem Yearly Susceptibility Test Information Collection Program is a 9-year-old antimicrobial resistance surveillance network of more than 100 medical centers worldwide, including 15 sites in the United States (US) that monitors the susceptibility of Gram-negative and Gram-positive bacterial pathogens especially to carbapenems. In 2005, the antimicrobial activity of 11 broad-spectrum agents was assessed against 2910 bacterial isolates (2493 Gram-negative and 417 staphylococci) submitted from the US medical centers to a reference laboratory using Clinical and Laboratory Standards Institute susceptibility testing methods and interpretative criteria. Meropenem continued to demonstrate 1) high potency with MIC 90 values 4- to 16-fold lower than imipenem against the Enterobacteriaceae, 2) equal activity against Pseudomonas aeruginosa, 3) 2-fold less activity compared with imipenem against Acinetobacter spp., and 4) 4- to 8-fold less activity compared with imipenem against the oxacillin-susceptible staphylococci. The wide spectrum of activity for carbapenems against Enterobacteriaceae (1657 strains) was confirmed by the overall rank order by percentage susceptibility at breakpoint criteria: imipenem (98.9%) > meropenem (98.7%) > cefepime (97.6%) > piperacillin/tazobactam (92.0%) > ceftriaxone (91.2%) > aztreonam (90.6%) > gentamicin = tobramycin (90.5%) > ceftazidime (90.4%) > levofloxacin (84.9%) > ciprofloxacin (83.9%). Against Acinetobacter spp. isolates, only tobramycin (92.0% susceptible) and carbapenems (92.0–85.6%) exhibited acceptable levels of activity. A continued increase in the resistance rate for both ciprofloxacin and levofloxacin was observed with highest rates found among indole-positive Proteae species (36.5–33.3%) and Escherichia coli (21.6–20.4%) isolates, some documented by molecular typing methods as clonally related. Ongoing surveillance of meropenem and other broad-spectrum antimicrobial agents appears warranted to monitor the potency and spectrum of activity against indicated Gram-negative and-positive pathogens causing serious infections in the hospital setting, and to detect the emergence of new or novel resistance mechanisms that could compromise clinical utility (serine and metallo-carbapenemases).

A7.12 The efficacy and safety of tigecycline in the treatment of complicated intra-abdominal infections: Results of pooled clinical trial data

Cefditoren, a broad-spectrum orally administered cephalosporin ester, has documented in vitro efficacy against many Gram-positive and -negative pathogens and stability against clinically important β-lactamases. We have reviewed the microbiology and the pharmacokinetic/pharmacodynamic literature regarding the spectrum and potency of this newer agent against the major etiologic agents of community-acquired respiratory infection, (Streptococcus pneumoniae, Hemophilus influenzae and Moraxella catarrhalis), as well as the Enterobacteriaceae and non-enteric Gram-negative bacilli, staphylococci, and other anerobic and anaerobic Gram-positive cocci. The level of cefditoren activity against S. pneumoniae (MIC90, 0.5 μg/mL) was superior to all marketed oral cephalosporins and at least equal to amoxicillin ± clavulanate. H. influenzae (MIC90, 0.016–0.03 μg/mL) and M. catarrhalis (MIC90, 0.06–0.5 μg/mL) were also very susceptible to cefditoren. In contrast to cefixime and ceftibuten, cefditoren was active against oxacillin-susceptible staphylococci (MIC90, ≤ 1 μg/mL) at a level comparable to cefuroxime axetil, cefaclor or cefprozil. Enterococci, Pseudomonas aeruginosa and most anaerobes (Gram-negative) were not cefditoren-susceptible, but most Enterobacteriaceae, β-haemolytic and viridans group streptococci were highly susceptible. Furthermore, an overview of key in vitro susceptibility testing methods and issues including disk diffusion testing and Etest (AB BIODISK, Solna, Sweden) method accuracy, interpretive criteria, and pharmacodynamic considerations for the selection of a breakpoint concentration are provided. The rapid bactericidal nature of the antibacterial activity of cefditoren, its post antibiotic effect, penicillin binding protein targets, and extent of β-lactamase stability are all favorable qualities. In conclusion, this orally administered (BID) β-lactam possesses promise for use against commonly isolated problematic respiratory tract pathogens such as penicillin-non-susceptible pneumococci and β-lactamase-positive M. catarrhalis or H. influenzae. Success in the clinical trials will further define the role of cefditoren in this era of emerging resistant bacterial pathogens.

Antimicrobial susceptibility of the pathogens of bacteraemia in the UK and Ireland 2001-2002: the BSAC Bacteraemia Resistance Surveillance Programme.

To describe the current patterns of antimicrobial resistance in the major pathogens of bacteraemia in the UK and Ireland, to highlight any unexpected resistance patterns and to act as a reference baseline for future studies. In 2001 and 2002, 5092 blood culture isolates were collected by 29 laboratories distributed across the UK and Ireland. A single central laboratory re-identified the isolates and measured MICs by the BSAC agar dilution method. Oxacillin resistance was found in 42% of Staphylococcus aureus and 76% of coagulase-negative staphylococci. Streptococci were generally susceptible to beta-lactams, but tetracycline resistance was common (except in Streptococcus pneumoniae) and particularly common among group B isolates (82% resistant). Nine percent of S. pneumoniae had reduced susceptibility to penicillin (MICs 0.12-1 mg/L), but none required >/=2 mg/L for inhibition. High-level gentamicin resistance was seen in 43% of Enterococcus faecalis, often in combination with raised ciprofloxacin MICs (>/=32 mg/L), but these isolates remained susceptible to ampicillin and imipenem. Only linezolid and tigecycline showed in vitro potency against a large proportion of Enterococcus faecium. Vancomycin resistance was restricted to enterococci (20% of E. faecium, 3% of E. faecalis) and a single isolate of coagulase-negative staphylococci (0.2%, MIC of 8 mg/L). Escherichia coli isolates were commonly resistant to amoxicillin (56%) and tetracycline (88%) but remained susceptible to ceftazidime, piperacillin/tazobactam and imipenem. Extended-spectrum beta-lactamases were detected in 2% of E. coli (none in 2001, 3.2% in 2002), 5% of Klebsiella spp. and 8% of Enterobacter spp. Resistance rates of Pseudomonas aeruginosa to ciprofloxacin, ceftazidime, gentamicin, imipenem and piperacillin/tazobactam were between 4% and 7%. Among the newly licensed and developmental agents, there was no resistance to linezolid in Gram-positive organisms. Ertapenem had a wide spectrum, covering Enterobacteriaceae, streptococci and oxacillin-susceptible staphylococci. MICs of tigecycline were low for Gram-positive species and Enterobacteriaceae except Proteeae and Enterobacter spp. Antimicrobial resistance among major bloodstream pathogens to those antimicrobials often selected for empirical therapy was relatively uncommon in 2001-2002, usually <10%. An important exception was oxacillin resistance in S. aureus.

In Vitro Antimicrobial Activity of Doripenem, a New Carbapenem

The doripenem MICs at which 90% of the tested strains were inhibited ranged from 0.03 to 1 microg/ml for 10 species of Enterobacteriaceae (n = 351), from 0.03 to 0.12 microg/ml for oxacillin-susceptible staphylococci (n = 119), from 4 to 32 microg/ml for oxacillin-resistant staphylococci (n = 64), from < or =0.008 to 0.06 microg/ml for penicillin-susceptible streptococci (n = 132), and from 1 to 4 microg/ml for penicillin-resistant streptococci (n = 51). Overall, doripenem demonstrated in vitro activity similar to that of meropenem against gram-negative pathogens and to that of imipenem against gram-positive pathogens.

Results from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme: report of the 2001 data from 15 United States medical centres

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme is an international surveillance network of more than 100 medical centres where meropenem is the primary therapeutic carbapenem. Institutions have been monitored since 1997 (1999 in United States (US)) using National Committee for Clinical Laboratory Standards (NCCLS) reference susceptibility methods to monitor in vitro activity of meropenem and selected other broad-spectrum antimicrobial agents. In 2001, a total of 2874 strains were processed from the 15 US medical centres. Molecular methods were associated with MIC methods as needed for defining epidemic spread of resistant strains. The meropenem MIC 90 values were 0.03 mg/l for Citrobacter spp., Escherichia coli and Klebsiella spp.; 0.06 mg/l for Proteus mirabilis and Serratia spp. and 0.12 mg/l for Enterobacter spp. This potency was 8–16-fold greater than that of imipenem and the meropenem spectrum of activity versus the Enterobacteriaceae was the broadest of all tested antimicrobial agents. Only piperacillin/tazobactam (MIC 9, 64 mg/l) and tobramycin (MIC 90, 4 mg/l) were active against more than 90.0% of Pseudomonas aeruginosa at the NCCLS susceptible breakpoint, and the carbapenems were the most active compounds against Acinetobacter spp. However, Acinetobacter spp. isolates were resistant to all of the antimicrobial agents tested and the molecular typing results suggested that they were epidemiologically related. Only ciprofloxacin and ceftazidime had significantly reduced activity against oxacillin-susceptible staphylococci (87.9–92.6% susceptible. These 2001 US MYSTIC Programme results demonstrated no significant decline in carbapenem activity or susceptibility rates compared with the previously monitored years (1999–2000). Most apparent were the decreasing susceptibility rates for ciprofloxacin and ceftazidime against staphylococci. Continued surveillance in these institutions appears warranted as sites of high potential emerging resistance risk.

KMP011 Molecular identification of a recurrent Listeria monocytogenes aortic graft infection

The need for comprehensive and quantitative accurate antimicrobial resistance surveillance systems has become acute as a guide to problem recognition and to focus local interventions. A multilaboratory (10 medical centers) Colombia surveillance project was initiated in early 1997 to monitor the potency and spectrum of six (cefepime, cefotaxime, ceftazidime, cefoperazone/sulbactam, aztreonam, and imipenem) broad-spectrum antimicrobial agents tested against 100 organisms per participant center (802 strains). Ten groups of organisms were tested by a reference-quality method (Etest; AB BIODISK, Solna, Sweden) with results validated by concurrent quality control and additional challenge strain analysis. Results from nine qualifying medical centers were tabulated, and 95.7 to 96.8% of quality assurance tests were within expected ranges. Only cefepime (90.1–100.0% susceptible) and imipenem (96.3–100.0%) were active against all Enterobacteriaceae at >90% of susceptible isolates using the breakpoint concentrations recommended by the National Committee for Clinical Laboratory Standards. Among ceftazidime- (or cefotaxime- or aztreonam-) resistant Enterobacter spp. and Citrobacter freundii, cefepime remained active, but not cefoperazone with sulbactam. Escherichia coli and Klebsiella spp. strains having resistance phenotypes consistent with extended spectrum β-lactamase production were discovered in approximately 5 to 10% of isolates. All tested drugs except ceftazidime (31.8–57.7% susceptible) were active against >94% of oxacillin-susceptible staphylococci. Similar rates of resistance (9.1–14.8%) were observed in Pseudomonas aeruginosa for five of six drugs (not cefotaxime; 15.9% of strains were susceptible). Acinetobacter spp. isolates were most susceptible to imipenem (95.8%), cefepime (86.1%), and cefoperazone/sulbactam (83.3%). Overall for the 1997 order of antimicrobial spectrums for these tested compounds was: imipenem (96.6%) > cefepime (93.6%) > cefoperazone/sulbactam (90.5%) > cefotaxime (74.9%) > aztreonam (74.3% for Gram-negative bacilli only) > ceftazidime (73.2%). These data should be used to guide empiric regimens in Colombia, and additionally will provide a resistance statistical baseline to which future studies in this nation can be compared.

Ertapenem: A parenteral, long-acting carbapenem

Ertapenem is a parenteral carbapenem that was licensed in the United States in November 2001. It is highly active in vitro against oxacillin-susceptible staphylococci, Streptococcus pneumoniae, β-hemolytic streptococci, Haemophilus spp., Moraxella catarrhalis, Enterobacteriaceae, and anaerobes but has limited activity against enterococci, Pseudomonas aeruginosa, and other nonfermentative gram-negative bacilli. Based on this spectrum of activity, ertapenem is most appropriate for treating community-acquired infections; it should not be used for empiric treatment of infections acquired in an intensive-care unit. Ertapenem is administered either intravenously or intramuscularly and has an elimination half-life of approximately 4 h. The recommended dose is 1 g once a day. No dose adjustment is required for elderly adults or patients with mild to moderate renal insufficiency; however, for patients with a creatinine clearance of ≤30 ml/min, a dose of 500 mg once a day is recommended. In large, adequately powered, clinical trials, ertapenem was shown to be highly effective for treating adults with complicated intra-abdominal infection, complicated skin/skin structure infection, acute pelvic infection, complicated urinary tract infection, or community-acquired pneumonia.

Comparative activity and spectrum of broad-spectrum β-lactams (cefepime, ceftazidime, ceftriaxone, piperacillin/tazobactam) tested against 12,295 staphylococci and streptococci: report from the SENTRY antimicrobial surveillance program (North America: 2001-2002)

A contemporary collection of 12,295 North American isolates (2001-2002) consisting of Staphylococcus aureus (50%), coagulase-negative staphylococci (12%), Streptococcus pneumoniae (24%), β-hemolytic streptococci (12%), and viridans-group streptococci (2%) were tested against broad-spectrum β-lactams (cefepime, ceftazidime, ceftriaxone, imipenem, piperacillin/tazobactam) and comparator agents using a reference broth microdilution method to determine their continued effectiveness for empiric antimicrobial therapy. All isolates were very susceptible to vancomycin, linezolid and quinupristin/dalfopristin (>98%). Oxacillin-susceptible staphylococci were also highly susceptible to the tested β-lactams (>98%) with the exception of ceftazidime (93%). β-hemolytic streptococci were exquisitely susceptible (>99%) to penicillin and all other agents except for clindamycin (94%) and erythromycin (81%). Viridans group streptococci were routinely less susceptible than were other streptococci. S. pneumoniae remained susceptible to most agents (>91%) with the exceptions of erythromycin (74%) and penicillin (69%). Among β-lactams tested against S. pneumoniae, ceftriaxone and cefepime continued to be very active against penicillin-susceptible (>99%) and intermediate (>98%) strains, but less active (80% and 82%, respectively) against penicillin-resistant isolates. These findings confirm that the newer cephalosporins (cefepime and ceftriaxone) among broad-spectrum β-lactam agents have a spectrum of activity that remains comprehensive for the commonly isolated Gram-positive pathogens.

Un Aggiornato Profilo di Sicurezza della Moxifloxacina

The study was initiated to determine the in vitro activity and MIC/disk test comparisons of BMS284756, a new des-fluoro(6)-quinolone, against isolates of staphylococci and enterococci from the SENTRY Antimicrobial Surveillance Program, 2000. Isolates were tested by reference broth microdilution and standardized disk diffusion methods. Against 3,789 strains of gram-positive cocci from the SENTRY Program (2000), the BMS284756 MIC90 and percentage susceptible at < or = 2 and < or = 4 microg/ml were: Staphylococcus aureus (4 microg/ml; 89.3 and 97.1%), coagulase-negative staphylococci (CoNS; 4 microg/ml; 86.1 and 96.0%) and enterococci (> 4 microg/ml; 62.0 and 76.2%). Also tested were selected staphylococci (300 strains) and enterococci (102 strains) by two standardized methods. The activity of BMS284756 was highly correlated with oxacillin resistance among staphylococci. Oxacillin-susceptible staphylococci were all inhibited by BMS284756 at < or = 0.5 microg/ml, whereas oxacillin-resistant strains required inhibitory concentrations of > or = 1 microg/ml. Excellent correlation was observed between the MIC and 5-microg disk zone diameter for staphylococci and enterococci (r=0.91 to 0.93). Among vancomycin-susceptible enterococci, 67% of Enterococcus faecalis, 25% of E. faecium, and 76% of other Enterococcus spp. isolates were inhibited by BMS284756 at < or = 2 microg/ml. All vancomycin-resistant enterococci (VRE; 11 E. faecalis and 15 E. faecium) were inhibited by > or = 2 microg/ml of BMS284756. Among the non-VRE, non-faecium enterococcal isolates (n=64), 62% were inhibited by < or = 0.5 microg/ml. BMS284756 showed excellent activity against oxacillin-susceptible staphylococci and moderate activity against enterococci other than VRE and E. faecium. Acceptable correlations were observed between MIC and disk test results for both tested genus groups.

Antimicrobial resistance trends in medical centers using carbapenems: report of 1999 and 2000 results from the MYSTIC program (USA)

Trends in susceptibility to antimicrobials were assessed from United States participants using 4488 isolates in the MYSTIC Program, 1999 (10 centers) through 2000 (15 centers). Diverse types of hospitals (general service, university, cancer, federal, pediatric, cystic fibrosis) were enrolled from 13 states. In 2000, oxacillin-susceptible staphylococci were 100% susceptible to meropenem, imipenem, and cefepime; but only 88% of strains were susceptible to ceftazidime. Among Enterobacteriaceae, ≥96% of Enterobacter spp., Citrobacter spp., and Serratia spp. were susceptible to meropenem, imipenem, and cefepime; but ceftazidime, ceftriaxone, and piperacillin/tazobactam had 5–20% resistance rates. Extended-spectrum β-lactamase resistance rates in Klebsiella spp. and Escherichia coli (6–7% and 3–5%, respectively) were stable over 2 years. Acinetobacter spp. were 78–81% susceptible to carbapenems but only 63–72% susceptible to ciprofloxacin. Meropenem, tobramycin, and piperacillin/tazobactam were the most active against Pseudomonas aeruginosa, but ciprofloxacin inhibited only 74% in 2000. Overall, meropenem remained the most potent agent, especially against ceftazidime- or piperacillin/tazobactam-resistant strains.

Cefditoren in vitro activity and spectrum: a review of international studies using reference methods

Cefditoren, a broad-spectrum orally administered cephalosporin ester, has documented in vitro efficacy against many Gram-positive and -negative pathogens and stability against clinically important β-lactamases. We have reviewed the microbiology and the pharmacokinetic/pharmacodynamic literature regarding the spectrum and potency of this newer agent against the major etiologic agents of community-acquired respiratory infection, ( Streptococcus pneumoniae, Hemophilus influenzae and Moraxella catarrhalis), as well as the Enterobacteriaceae and non-enteric Gram-negative bacilli, staphylococci, and other anerobic and anaerobic Gram-positive cocci. The level of cefditoren activity against S. pneumoniae (MIC 90, 0.5 μg/mL) was superior to all marketed oral cephalosporins and at least equal to amoxicillin ± clavulanate. H. influenzae (MIC 90, 0.016–0.03 μg/mL) and M. catarrhalis (MIC 90, 0.06–0.5 μg/mL) were also very susceptible to cefditoren. In contrast to cefixime and ceftibuten, cefditoren was active against oxacillin-susceptible staphylococci (MIC 90, ≤ 1 μg/mL) at a level comparable to cefuroxime axetil, cefaclor or cefprozil. Enterococci, Pseudomonas aeruginosa and most anaerobes (Gram-negative) were not cefditoren-susceptible, but most Enterobacteriaceae, β-haemolytic and viridans group streptococci were highly susceptible. Furthermore, an overview of key in vitro susceptibility testing methods and issues including disk diffusion testing and Etest (AB BIODISK, Solna, Sweden) method accuracy, interpretive criteria, and pharmacodynamic considerations for the selection of a breakpoint concentration are provided. The rapid bactericidal nature of the antibacterial activity of cefditoren, its post antibiotic effect, penicillin binding protein targets, and extent of β-lactamase stability are all favorable qualities. In conclusion, this orally administered (BID) β-lactam possesses promise for use against commonly isolated problematic respiratory tract pathogens such as penicillin-non-susceptible pneumococci and β-lactamase-positive M. catarrhalis or H. influenzae. Success in the clinical trials will further define the role of cefditoren in this era of emerging resistant bacterial pathogens.

In vitro activity of selected cephalosporins and erythromycin against staphylococci and pneumococci isolated at 38 North American medical centers participating in the SENTRY Antimicrobial Surveillance Program, 1997-1998.

The SENTRY Antimicrobial Surveillance Program employs a worldwide network of hospitals to monitor the predominant bacterial and fungal pathogens and antimicrobial susceptibility patterns associated with nosocomial and community-acquired bloodstream, respiratory tract, wound, and urinary tract infections. The purpose of this analysis of SENTRY data is to extract information on the current North American susceptibility patterns of pneumococci and oxacillin-susceptible staphylococci from the comprehensive SENTRY program database. Clinical isolates were provided by 30 centers in the United States (grouped into five regions) and eight centers in Canada. Susceptibility testing was performed at a central reference laboratory using broth microdilution methods and interpretive criteria specified by the National Committee for Clinical Laboratory Standards. Of 34 530 North American bacterial isolates tested during 1997 and 1998, 565 (1.6%) were oxacillin-susceptible, coagulase-negative staphylococci (CoNS). Cefazolin, cefepime, and ceftriaxone all had excellent activity against these CoNS (97.3%-99. 3% susceptible), and 90.4% were susceptible to ceftazidime. A total of 4404 isolates (12.8%) were oxacillin-susceptible Staphylococcus aureus. Overall, 98.9% to 99.2% were susceptible to cefazolin, cefepime, and ceftriaxone; ceftazidime did not have acceptable activity against these S. aureus. Streptococcus pneumoniae accounted for 1665 (4.8%) of North American SENTRY isolates. A total of 1212 isolates (72.8%) were fully susceptible to penicillin (MIC </= 0.06 microg/ml), 250 (15%) were penicillin intermediate (MIC 0.12-1 microg/ml), and 203 (12.2%) were penicillin resistant (MIC >/= 2 microg/ml). The rate of penicillin susceptibility was highest in Canada, and lowest in the South Central and South East regions of the United States. Cefepime, cefuroxime, ceftazidime, and erythromycin all demonstrated excellent efficacy (94%-99.8% susceptibility) against fully penicillin-susceptible isolates of S. pneumoniae. Among pneumococci with intermediate penicillin resistance, 88% were susceptible to cefepime, 92% to cefotaxime, and only 14% to ceftazidime. None of the antimicrobial agents in this analysis demonstrated adequate activity against fully penicillin-resistant pneumococci. In summary, the fourth-generation cephalosporin, cefepime, demonstrated consistently excellent efficacy against oxacillin-susceptible staphylococci and most pneumococci, and remains an appropriate choice for empiric therapy of serious infections.

In vitro evaluation of cefepime and other broad-spectrum β-lactams against bacteria from Indonesian medical centers

The in vitro activity of cefepime and six other broad-spectrum β-lactams (cefpirome, ceftazidime, ceftriaxone, imipenem, piperacillin/tazobactam (4 μg/mL fixed concentration), and oxacillin was evaluated against 191 isolates of clinical bacteria from Indonesia. Susceptibility testing was performed using Etest (AB BIODISK, Solna, Sweden) methodology. Isolates from 10 species groups were selected for analysis: Escherichia coli, Klebsiella spp., Enterobacter spp., indole-positive Proteae, Serratia spp., Acinetobacter spp., Pseudomonas aeruginosa, and oxacillin-susceptible staphylococci. The overall rank order of spectrum of activity was (% resistant): imipenem (2.2%) > cefepime (7.3%) > piperacillin/tazobactam > cefpirome > ceftazidime > ceftriaxone (16.2%). The “fourth-generation” cephalosporins, cefepime and cefpirome, displayed greater activity compared with the “third-generation” cephalosporins, ceftazidime, and ceftriaxone, against the 60 E. coli and Klebsiella spp. (30 each) isolates. Phenotypic extended spectrum β-lactamase occurrence rates among the E. coli and Klebsiella spp. were 23.3 and 33.3%, respectively. Imipenem, cefepime, and cefpirome inhibited 95.7% of the 46 isolates of inducible Amp C cephalosporinase producing Enterobacteriaceae. The majority of the resistance observed to imipenem and cefepime among tested Indoneisian strains was attributable to the nonfermentative Gram-negative bacilli, P. aeruginosa and Acinetobacter spp. These results indicate the presence of β-lactam resistance in Indonesia and the need for continued antimicrobial surveillance in this nation and region of the world, preferably using accurate quantitative methods.

In vitro evaluation of cefepime and other broad-spectrum β-lactams for isolates in Malaysia and Singapore medical centers

The degree of activity of several β-lactam antimicrobial agents was assessed in Malaysia (four medical centers) and Singapore (two medical centers) tested against 570 clinical isolates. The organisms were tested locally by the Etest (AB BIODISK, Solna, Sweden) method, validated by concurrent use of quality assurance strains (94.1% accurate performance overall). Ten groups of bacteria were tested against cefepime, cefpirome, ceftazidime, ceftriaxone, piperacillin/tazobactam, oxacillin, and imipenem. Among the tested Escherichia coli and Klebsiella spp., the occurrence of extended spectrum β-lactamase-producing phenotypes was 5.6–7.0% and 36.7–38.0%, respectively. These strains remained most susceptible (97.5–100.0%) to cefepime and imipenem. Ceftazidime-resistant Enterobacter spp. (21.4% resistant), Citrobacter spp. (15.0%), indole-positive Proteus spp. (6.0%), and Serratia spp. (9.7%) were not resistant to cefepime, and only one strain was resistant to imipenem. Imipenem was generally most potent against nonfermentative Gram-negative bacilli such as Acinetobacter spp. and Pseudomonas aeruginosa. All tested β-lactams were active against the oxacillin-susceptible staphylococci, except ceftazidime (MIC 90, 12 μg/mL; 63.2–84.8% susceptibility rates). Overall spectrums of activity (rank by % resistance) favored imipenem (3.5%) > cefepime (7.7%) > cefpirome (8.9%) > piperacillin/tazobactam (13.2%) > ceftriaxone (14.7%) > ceftazidime (16.9%). No significant differences in resistance patterns were noted between monitored nations, and these results indicate emerging, elevated rates of resistance versus the studied broad-spectrum β-lactams in Malaysia and Singapore. Results provide benchmark data for future studies using quantitative methods to determine antimicrobial resistance in these geographic areas.