Antimicrobial susceptibility of clinical isolates of Neisseria gonorrhoeae to alternative antimicrobials with therapeutic potential.

Background: The prevalence of MDR Neisseria gonorrhoeae is increasing globally and represents a public health emergency. Development and approval of new anti-gonococcal agents may take years. As a concurrent approach to developing new antimicrobials, the laboratory and clinical evaluation of currently licensed antimicrobials not widely used for the treatment of gonorrhoea may provide new options for the treatment of gonococcal infections. Objectives: To determine the in vitro activity of nine alternative, currently licensed and late-development antimicrobials with the potential to treat gonococcal infections against 112 clinical isolates of N. gonorrhoeae resistant to one or multiple antimicrobials. Methods: The MICs of conventional anti-gonococcal antimicrobials (penicillin, ceftriaxone, cefixime, azithromycin, ciprofloxacin, tetracycline and spectinomycin) and alternative antimicrobials (ertapenem, gentamicin, netilmicin, tigecycline, eravacycline, fosfomycin, linezolid, ceftazidime/avibactam and ceftaroline) were determined by agar dilution. Results: Ertapenem and the novel cephalosporins demonstrated similar MIC values to the third-generation cephalosporins, but increased MICs were observed for isolates with increased cefixime and ceftriaxone MICs. Tigecycline and eravacycline had MIC values below expected serum concentrations for all isolates tested. The aminoglycosides gentamicin and netilmicin were generally more potent than spectinomycin, with netilmicin demonstrating the greatest potency. Fosfomycin MICs were elevated compared with other agents, but remained within the MIC range for susceptible organisms, while linezolid MICs were generally higher than those for organisms considered resistant. Conclusions: Among potentially therapeutically useful alternative agents, the aminoglycosides, eravacycline, tigecycline and fosfomycin had good in vitro activity. The novel cephalosporins and ertapenem had comparable activity to cefixime and ceftriaxone.

Epidemiology of vancomycin-resistant enterococci in Canadian hospitals (CANWARD study, 2007 to 2013).

Of 1,927 Enterococcus species isolates collected across Canada from 2007 to 2013, 80 (4.2%) were identified as vancomycin-resistant enterococci (VRE). VRE infections during this time tripled in Canadian hospitals, from 1.8% to 6.0% (P = 0.03). All VRE were Enterococcus faecium, with 90% possessing vanA. The prevalence of vanB decreased from 37.5% in 2007 to 0% in 2013 (P < 0.05). The VRE were multidrug resistant, but 70.6%, 86.3%, and 100% were susceptible to doxycycline, linezolid, and daptomycin, respectively.

In vitro activity of plazomicin against 5,015 gram-negative and gram-positive clinical isolates obtained from patients in canadian hospitals as part of the CANWARD study, 2011-2012.

Plazomicin is a next-generation aminoglycoside that is not affected by most clinically relevant aminoglycoside-modifying enzymes. The in vitro activities of plazomicin and comparator antimicrobials were evaluated against a collection of 5,015 bacterial isolates obtained from patients in Canadian hospitals between January 2011 and October 2012. Susceptibility testing was performed using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method, with MICs interpreted according to CLSI breakpoints, when available. Plazomicin demonstrated potent in vitro activity against members of the family Enterobacteriaceae, with all species except Proteus mirabilis having an MIC90 of ≤1 µg/ml. Plazomicin was active against aminoglycoside-nonsusceptible Escherichia coli, with MIC50 and MIC90 values identical to those for aminoglycoside-susceptible isolates. Furthermore, plazomicin demonstrated equivalent activities versus extended-spectrum ß-lactamase (ESBL)-producing and non-ESBL-producing E. coli and Klebsiella pneumoniae, with 90% of the isolates inhibited by an MIC of ≤1 µg/ml. The MIC50 and MIC90 values for plazomicin against Pseudomonas aeruginosa were 4 µg/ml and 16 µg/ml, respectively, compared with 4 µg/ml and 8 µg/ml, respectively, for amikacin. Plazomicin had an MIC50 of 8 µg/ml and an MIC90 of 32 µg/ml versus 64 multidrug-resistant P. aeruginosa isolates. Plazomicin was active against methicillin-susceptible and methicillin-resistant Staphylococcus aureus, with both having MIC50 and MIC90 values of 0.5 µg/ml and 1 µg/ml, respectively. In summary, plazomicin demonstrated potent in vitro activity against a diverse collection of Gram-negative bacilli and Gram-positive cocci obtained over a large geographic area. These data support further evaluation of plazomicin in the clinical setting.

In vitro activity of ceftolozane-tazobactam against Pseudomonas aeruginosa isolates obtained from patients in Canadian hospitals in the CANWARD study, 2007 to 2012.

The in vitro activity of ceftolozane in combination with tazobactam (fixed concentration of 4 µg/ml) was evaluated against 2,435 Pseudomonas aeruginosa clinical isolates obtained from across Canada using Clinical and Laboratory Standards Institute broth microdilution methods. The MIC50 and MIC90 values for ceftolozane-tazobactam were 0.5 µg/ml and 1 µg/ml, respectively (a 32-fold-lower MIC90 than that for ceftazidime). Eighty-nine percent (141/158) of multidrug-resistant isolates were inhibited by ≤8 µg/ml of ceftolozane-tazobactam.

Change in antimicrobial susceptibility of Escherichia coli urinary tract isolates at a single institution over a period of 10 years.

Urinary tract infections are common. Few published studies have demonstrated the change in Escherichia coli urinary isolate antimicrobial susceptibility over time within a given area and (or) population. The purpose of this study was to evaluate the change in susceptibility of E. coli clinical isolates obtained from urine specimens at a single institution over a period of 10 years. The microbiology laboratory information system at St. Boniface Hospital (Winnipeg, Manitoba, Canada) was searched retrospectively from 1 January 2000 to 31 December 2009, for all E. coli isolates from either a midstream or catheter urine source that had susceptibility testing performed. Only one isolate per patient was included during the entire study period. Antimicrobial susceptibility testing was carried out with either a Microscan instrument (pre-April 2004) or a Vitek instrument (May 2004 onwards). In total, 7353 E. coli urinary isolates were included for evaluation. Ciprofloxacin susceptibility declined significantly, from 99% in 2000 to 85% in 2009 (p < 0.0001). A small but statistically significant decline in susceptibility was also observed for ampicillin, cefazolin, trimethoprim-sulfamethoxazole, gentamicin, and nitrofurantoin. These data suggest that certain antimicrobials recommended for the treatment of urinary tract infections (ciprofloxacin, trimethoprim-sulfamethoxazole) may no longer be optimal.

Activity of NXL104 in combination with beta-lactams against genetically characterized Escherichia coli and Klebsiella pneumoniae isolates producing class A extended-spectrum beta-lactamases and class C beta-lactamases.

The novel non-ß-lactam ß-lactamase inhibitor NXL104, in combination with cefepime, ceftazidime, ceftriaxone, amdinocillin, and meropenem, was tested against 190 extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates, 94 AmpC-hyperproducing E. coli isolates, and 8 AmpC/ESBL-coexpressing E. coli isolates. NXL104 restored 100% susceptibility to the partner cephalosporins for all isolates tested. Amdinocillin and meropenem MICs were modestly improved (2 to 32 times lower) by NXL104. These results suggest that NXL104 may be useful in combination with ß-lactams for the treatment of infections caused by ESBL- and AmpC-producing Enterobacteriaceae.

In vitro activity of ceftazidime combined with NXL104 versus Pseudomonas aeruginosa isolates obtained from patients in Canadian hospitals (CANWARD 2009 study).

The in vitro activity of ceftazidime in combination with NXL104 versus 470 Pseudomonas aeruginosa clinical isolates was evaluated using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods. Ceftazidime had MIC90s of 8 µg/ml and 32 µg/ml in the presence and absence of NXL104, respectively. Of 25 multidrug-resistant P. aeruginosa isolates, the percentages with a ceftazidime MIC of ≤8 µg/ml with and without NXL104 were 60% and 4%, respectively. These data suggest that the ceftazidime-NXL104 combination may prove useful for treating many P. aeruginosa infections.

In vitro activity of colistin (polymyxin E) against 3,480 isolates of gram-negative bacilli obtained from patients in Canadian hospitals in the CANWARD study, 2007-2008.

The in vitro activity of colistin was evaluated versus 3,480 isolates of gram-negative bacilli using CLSI broth microdilution methods. The MIC(90) of colistin was < or = 2 microg/ml against a variety of clinically important gram-negative bacilli, including Escherichia coli, Klebsiella spp., Enterobacter spp., Acinetobacter baumannii, and Pseudomonas aeruginosa. All multidrug-resistant (n = 76) P. aeruginosa isolates were susceptible to colistin (MIC, < or = 2 microg/ml). These data support a role for colistin in the treatment of infections caused by multidrug-resistant P. aeruginosa.

Identification of multidrug- and carbapenem-resistant Acinetobacter baumannii in Canada: results from CANWARD 2007.

OBJECTIVES: Multidrug-resistant (MDR) Acinetobacter baumannii is a growing concern in many countries. This report describes patient demographics, antimicrobial susceptibilities and molecular characteristics of A. baumannii cases identified through the Canadian Ward Surveillance Study (CANWARD). In addition, clinical cases involving MDR carbapenem-resistant A. baumannii are also detailed in this report. METHODS: From January to December 2007, 12 hospital centres across Canada submitted pathogens from clinics, emergency rooms, intensive care units and medical/surgical wards as part of the CANWARD study. MICs were determined using microbroth dilution (CLSI). PCR and sequence analysis identified OXA genes among carbapenem-resistant isolates. PFGE was used to determine genetic relatedness and compare representatives of the Midlands 2 strain, OXA-23 clone 1 or 2, T strains and isolates collected from military sources. RESULTS: This study identified A. baumannii in 0.33% (n = 26) of infections. The majority of isolates remained susceptible to the antimicrobials tested, however, 7.7% (n = 2) displayed an MDR phenotype, including resistance to carbapenems. In one isolate bla(OXA-58) was found to be the likely cause of carbapenem resistance while the other isolate had an insertion sequence element upstream of its intrinsic bla(OXA-51). The clinical data of these two isolates suggest that one is travel-related while the source of the other remains unknown. CONCLUSIONS: A. baumannii infections from Canadian hospitals were relatively low. Carbapenem-resistant MDR A. baumannii were also rare and unrelated to previously observed isolates from military sources. Continued surveillance in Canada is suggested in order to determine if such organisms will become a problem.

Review of macrolides and ketolides: focus on respiratory tract infections.

The first macrolide, erythromycin A, demonstrated broad-spectrum antimicrobial activity and was used primarily for respiratory and skin and soft tissue infections. Newer 14-, 15- and 16-membered ring macrolides such as clarithromycin and the azalide, azithromycin, have been developed to address the limitations of erythromycin. The main structural component of the macrolides is a large lactone ring that varies in size from 12 to 16 atoms. A new group of 14-membered macrolides known as the ketolides have recently been developed which have a 3-keto in place of the L-cladinose moiety. Macrolides reversibly bind to the 23S rRNA and thus, inhibit protein synthesis by blocking elongation. The ketolides have also been reported to bind to 23S rRNA and their mechanism of action is similar to that of macrolides. Macrolide resistance mechanisms include target site alteration, alteration in antibiotic transport and modification of the antibiotic. The macrolides and ketolides exhibit good activity against gram-positive aerobes and some gram-negative aerobes. Ketolides have excellent activity versus macrolide-resistant Streptococcus spp. Including mefA and ermB producing Streptococcus pneumoniae. The newer macrolides, such as azithromycin and clarithromycin, and the ketolides exhibit greater activity against Haemophilus influenzae than erythromycin. The bioavailability of macrolides ranges from 25 to 85%, with corresponding serum concentrations ranging from 0.4 to 12 mg/L and area under the concentration-time curves from 3 to 115 mg/L x h. Half-lives range from short for erythromycin to medium for clarithromycin, roxithromycin and ketolides, to very long for dirithromycin and azithromycin. All of these agents display large volumes of distribution with excellent uptake into respiratory tissues and fluids relative to serum. The majority of the agents are hepatically metabolised and excretion in the urine is limited, with the exception of clarithromycin. Clinical trials involving the macrolides are available for various respiratory infections. In general, macrolides are the preferred treatment for community-acquired pneumonia and alternative treatment for other respiratory infections. These agents are frequently used in patients with penicillin allergies. The macrolides are well-tolerated agents. Macrolides are divided into 3 groups for likely occurrence of drug-drug interactions: group 1 (e.g. erythromycin) are frequently involved, group 2 (e.g. clarithromycin, roxithromycin) are less commonly involved, whereas drug interactions have not been described for group 3 (e.g. azithromycin, dirithromycin). Few pharmacoeconomic studies involving macrolides are presently available. The ketolides are being developed in an attempt to address the increasingly prevalent problems of macrolide-resistant and multiresistant organisms.

North American (United States and Canada) comparative susceptibility of two fluoroquinolones: ofloxacin and ciprofloxacin. A 53-medical-center sample of spectra of activity. North American Ofloxacin Study Group.

Ofloxacin, a newer broad-spectrum fluoroquinolone, was evaluated against > 12,000 clinical isolates in a multicenter surveillance trial in the United States and Canada using the standardized disk diffusion method. A total of 53 geographically diverse clinical microbiology laboratories contributed zone diameter results for ofloxacin, ciprofloxacin, and norfloxacin for urinary tract infection (UTI) isolates; and ofloxacin and ciprofloxacin for respiratory tract infection (RTI) isolates, skin and soft tissue infection (SSTI) isolates, and genital tract pathogen isolates. In both the USA and Canada, ofloxacin was shown to have the wide spectrum of activity as follows: RTI isolates, ofloxacin (92.2%-93.8% susceptible) > ciprofloxacin (89.5%-90.4%); SSTI isolates, ofloxacin (87.1%-93.6%) > ciprofloxacin (78.8%-90.4%); UTI isolates, ofloxacin (91.6%-92.5%) > norfloxacin (87.3%-91.7%) > ciprofloxacin (86.4%-89.7%); and genital tract isolates, ofloxacin (94.0%) > ciprofloxacin (85.4%) (Canada only). US strains resistant to ofloxacin were confirmed by reference laboratory tests. Confirmed ofloxacin resistance, other than among staphylococci or nonenteric bacilli, was rare. The species most often found to be resistant to both ofloxacin and ciprofloxacin were methicillin-resistant staphylococci, Acinetobacter spp., and Enterococcus spp. From these contributing US and Canadian laboratory studies, ofloxacin appears to have a balanced spectrum of potential clinical use (91.8% susceptible aerobic isolates), particularly against Gram-positive pathogens and some species resistant to ciprofloxacin. The combined overall isolate (12,241 isolates) rates of susceptibility for ciprofloxacin (four infection sites) and norfloxacin (UTI only) were 87.3% and 88.8%, respectively. Monitoring for increasing fluoroquinolone resistance should be considered, however, as greater use of drugs in this class develops.

Bacterial antigen detection in cerebrospinal fluid of patients with meningitis.

This study compared the sensitivity and specificity of four test systems in detecting Haemophilus influenzae type b, Neisseria meningitidis, Streptococcus pneumoniae, and gram-negative organisms in cerebrospinal fluid (CSF), versus culture. The tests used on CSF from 155 patients with meningitis were the Phadebact coagglutination (CoA) test, the Directigen latex agglutination (LA) test, counterimmunoelectrophoresis (CIE), and the Limulus amebocyte lysate (LAL) test. The sensitivity for patients with bacterial meningitis was 78% (18/23) for LA, 78% (25/32) for CoA, and 67% (18/27) for CIE for detection of H. influenzae type b; 71% (10/14) for CoA, 100% (6/6) for LA, and 50% (6/13) for CIE in detecting S. pneumoniae; and 33% (1/3) for LA and 50% (2/4) for CIE in detecting N. meningitidis. LAL had a sensitivity of 77% (37/48) in detecting CSF gram-negative endotoxin. The specificities of those with bacterial meningitis for H. influenzae, S. pneumoniae, and N. meningitidis tested by LA were, respectively, 100% (35/35), 96% (50/52), and 100% (54/54); for H. influenzae and S. pneumoniae using CoA 97% (62/64) and 96% (80/83); for H. influenzae, S. pneumoniae, and N. meningitidis using CIE 67% (18/27), 50% (6/12), and 50% (2/4). The specificity of LAL was 86% (38/44). The detection of bacterial antigen from CSF in patients with meningitis by commercial agglutination tests is more sensitive than CIE and is highly specific.

Comparison of the activity of two broad-spectrum cephalosporins tested against 2,299 strains of Pseudomonas aeruginosa isolated at 38 North American medical centers participating in the SENTRY Antimicrobial Surveillance Program, 1997-1998.

Pseudomonas aeruginosa is an important nosocomial pathogen. Resistance to certain beta-lactam antimicrobial agents among P. aeruginosa is increasing. The SENTRY Antimicrobial Surveillance Program was designed to employ a network of hospitals in the United States, Canada, Latin America, and Europe to monitor the predominant bacterial and fungal pathogens and antimicrobial susceptibility patterns associated with community-acquired and nosocomial bloodstream, respiratory tract, wound, and urinary tract infections. The purpose of this analysis of SENTRY results was to extract information on the current North American susceptibility pattern of P. aeruginosa for two antipseudomonal cephalosporins, ceftazidime, and cefepime. 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 by using broth microdilution methods and interpretive criteria specified by the National Committee for Clinical Laboratory Standards. Of the 34, 530 North American bacterial isolates tested during 1997 and 1998, 2299 (6.7%) were P. aeruginosa. There were no substantial differences in regional rates of P. aeruginosa susceptibility to ceftazidime (range 78.8-81.9%) or cefepime (range 80.0-83.4%) The percentage of resistant isolates among the 1784 United States isolates was 13.3% for ceftazidime versus 7.1% for cefepime (p < 0.05). It is essential to continue surveillance of the in vitro efficacy of these and other beta-lactam agents against P. aeruginosa because of the clinical importance of these safe and broad-spectrum cephems used alone or in combination in current clinical practice.

In vitro activities of six fluoroquinolones against Canadian isolates of vancomycin-sensitive and vancomycin-resistant Enterococcus species.

The in vitro activities of six fluoroquinolones were determined against 1482 Enterococcus species isolates collected as part of a 1996 Canadian surveillance study. Clinafloxacin MIC90s were 4 or 8 microg/mL, trovafloxacin and BAY 12-8039 MIC90s were 8 or 16 microg/mL, sparfloxacin MIC90s were 32 microg/mL, and ciprofloxacin and ofloxacin MIC90s were >32 microg/mL for the vancomycin-sensitive Enterococcus faecalis, vancomycin-sensitive Enterococcus faecium, and vancomycin-resistant E. faecium isolates collected.

Vancomycin-resistant enterococci (VRE) colonization of high-risk patients in tertiary care Canadian hospitals. Canadian VRE Surveillance Group.

We isolated 1487 Enterococcus species from 1200 stool specimens collected from high-risk patients in 12 Canadian tertiary care hospitals between October 1995 and November 1996. The composition of the 1487 isolates was 601 vancomycin-sensitive Enterococcus faecalis (40.4%), 667 vancomycin-sensitive Enterococcus faecium (44.9%), 18 vancomycin-resistant (nine isolates MIC 8-16 micrograms/mL; nine isolates MIC > or = 32 micrograms/mL) E. faecium (VREF) (1.2%), 95 vancomycin-sensitive Enterococcus gallinarum (6.4%), 29 vancomycin-resistant (all MICs 8-16 micrograms/mL) E. gallinarum (2.0%), and 77 vancomycin-sensitive Enterococcus casseliflavus (5.2%). Nine of the 18 VREF isolates collected possessed the vanA genotype and were from three patients at one hospital. Two other VREF isolates, of the vanB genotype, were from a single patient at a second hospital, and the remaining seven isolates, also all of the vanB genotype, were from five patients at a third hospital. All VREF were ampicillin resistant (MIC > or = 16 micrograms/mL), streptomycin resistant (MIC > 1000 micrograms/mL), and ciprofloxacin resistant (MIC > or = 4 micrograms/mL). Ten of the 18 VREF were also resistant to gentamicin (MIC > 500 micrograms/mL), while all 18 isolates had quinupristin/dalfopristin MICs < or = 0.5 microgram/mL. In conclusion, high-risk patients in tertiary care Canadian hospitals are rarely colonized (9/1200 patients, 0.75%) with VREF in their lower gastrointestinal tract. These findings correlate well with the lack of reported VREF infection in high-risk patients in Canadian hospitals. Quinupristin/dalfopristin demonstrated excellent in vitro activity against VREF and other non-faecalis species of Enterococcus, many of which also possessed high-level ampicillin, and/or high-level aminoglycoside, and/or ciprofloxacin resistance.

In vitro activity of the novel ketolide HMR 3647 and comparative oral antibiotics against Canadian respiratory tract isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

The in vitro activities of HMR 3647, erythromycin A, clarithromycin, azithromycin, roxithromycin, penicillin G, ampicillin, cefuroxime, trimethoprim/sulfamethoxazole, tetracycline, ciprofloxacin, and levofloxacin were determined for 1179 Streptococcus pneumoniae, 1438 Haemophilus influenzae, and 428 Moraxella catarrhalis isolated from respiratory tract specimens by 18 medical centers across Canada during 1997-1998. On a per weight basis, HMR 3647 was the most active agent tested against S. pneumoniae with MIC90s of < or = 0.12 microgram/mL for both penicillin susceptible and penicillin intermediate isolates and 0.25 microgram/mL for penicillin-resistant isolates. HMR 3647 was also highly active against M. catarrhalis (MIC90, < or = 0.12 microgram/mL), but less active against H. influenzae (MIC90, 4 micrograms/mL).

Positive Bactec resin cultures do not influence antimicrobial selection.

We performed a retrospective evaluation of Bactec resin blood cultures, submitted to the clinical laboratories of the University of Manitoba teaching hospitals, to determine the impact positive cultures might have on the selection of antimicrobial therapy. Of the 2919 resin cultures submitted in 1987, 151 were positive, with 161 separate isolates. Of these cultures, 13 were reported after the death of the patient and 8 could not be adequately assessed because of insufficient clinical information. Four positive cultures were obtained from patients not receiving antimicrobial therapy. Forty-four cultures (53 isolates) from 37 patients were judged to be contaminants. Each of the remaining 82 clinically significant positive cultures were monomicrobial. Isolates from 34 cultures were resistant to the antibiotics being administered and might have been expected to grow in nonresin blood cultures. Forty-eight isolates from 18 patients were susceptible to the antibiotic(s) being administered at the time the culture was drawn. In none of these patients did the positive result lead to a change in the choice of antimicrobial therapy. In only one case was there an increase in antibiotic dosage. It appears that positive Bactec resin blood cultures do not have a significant impact on antimicrobial selection, and routine use may not be justified.

In vitro activity of three carbapenem antibiotics. Comparative studies with biapenem (L-627), imipenem, and meropenem against aerobic pathogens isolated worldwide.

The in vitro activity of biapenem (formerly L-627 or LJC10, 627), a new carbapenem, was compared with that of imipenem and meropenem against > 6000 clinically significant pathogens isolated in six countries worldwide. Biapenem was active against members of the family Enterobacteriaceae with a 90% minimum inhibitory concentration (MIC90) ranging from < or = 0.06 to 2 micrograms/ml. Only Serratia spp. and Providencia spp. were less susceptible (MIC90, 8 micrograms/ml). Pseudomonas aeruginosa and Xanthomonas maltophilia displayed an MIC90 of > or = 8 micrograms/ml biapenem/ml whereas Acinetobacter spp. were susceptible at < or = 1 micrograms/ml. Oxacillin-resistant staphylococci were resistant to biapenem at > 8 micrograms/ml whereas oxacillin-sensitive staphylococci were susceptible at < or = 1 micrograms/ml. Biapenem, imipenem, and meropenem displayed poor activity against Ent. faecium (MIC90, > or = 8 micrograms/ml), and only imipenem displayed slightly better activity against Ent. faecalis (MIC90, 4 micrograms/ml). The rank order of activity against groups of isolates was Enterobacteriaceae (meropenem > biapenem > or = imipenem), Ps. aeruginosa (biapenem = meropenem = imipenem), oxacillin-sensitive staphylococci (imipenem > or = biapenem = meropenem), oxacillin-resistant staphylococci (biapenem = meropenem = imipenem), and Enterococcus spp. (biapenem = meropenem = imipenem). These in vitro suggest that further developmental work on biapenem is warranted.

The North American component (the United States and Canada) of an International Comparative MIC trial monitoring ofloxacin resistance.

Common lots of reference MIC (minimum inhibitory concentration) method reagents were used to monitor ofloxacin, a newer fluoroquinolone, and 13 other drugs against 3200 recent clinical isolates in February-April 1992. Five medical centers in the United States and Canada contributed 640 strains per facility as follows: Escherichia coli, Staphylococcus aureus, coagulase-negative staphylococci, Klebsiella spp., and Pseudomonas aeruginosa (100 strains each); Streptococcus pneumoniae (40 strains); and Enterobacter cloacae, Serratia marcescens, Salmonella spp., Haemophilus influenzae, and Moraxella catarrhalis (20 strains each). Quality-control strains were processed concurrently, MICs recorded, and data processed at a common location. Selected ofloxacin-resistant isolates were retested at a reference laboratory to confirm resistances and determine cross-resistant patterns. Results indicate the following (a) fluoroquinolones were superior in usable spectrum of activity to other orally administered drugs (for example, cefaclor, cefixime, ampicillin, amoxicillin-clavulanate, minocycline, oxacillin, and trimethoprim-sulfamethoxazole); (b) ofloxacin and ciprofloxacin were generally equal to gentamicin and cefotaxime against commonly isolated Gram-negative pathogens; (c) fluoroquinolone resistance was rare among enteric bacilli, pneumococci (ciprofloxacin > ofloxacin), H. influenzae, and M. catarrhalis, but more common among oxacillin-resistant staphylococci and P. aeruginosa; (d) cross resistance was generally observed between ofloxacin and ciprofloxacin but was species or genus dependent; and (e) a new fluoroquinolone, levofloxacin, demonstrated promising activity against contemporary pathogens.