Barbara LeBlanc

Susceptibility surveillance among gram-negative bacilli at a cancer center

We conducted a survey of susceptibility among 758 gram-negative bacilli (GNB; collected from cancer patients over a 3-month period) to commonly used antibiotics. The overall resistance among GNB was least for piperacillin/tazobactam and meropenem (5 and 6%, respectively) followed by cefepime (8%), imipenem (9%), amikacin (12%), ofloxacin (13%), ciprofloxacin, ceftazidime and ticarcillin/clavulanate (14% each), aztreonam (18%) and tobramycin (24%). In comparison to data on antibiotic resistance to ceftazidime, imipenem, ciprofloxacin and aztreonam in similar studies in 1985 and 1994, resistance has significantly increased to all four antibiotic classes. Based on our current study, meropenem, cefepime, imipenem and piperacillin/tazobactam would be the most appropriate choices in our institution for empiric therapy of GNB infections in febrile neutropenic patients.

Susceptibilities of bacterial isolates from patients with cancer to levofloxacin and other quinolones.

The antibacterial activity of levofloxacin was compared with those of ofloxacin and ciprofloxacin against bacterial isolates from patients with cancer. In general, levofloxacin was as active or was twofold more active than ofloxacin and was two- to fourfold less active than ciprofloxacin against most gram-negative pathogens. Against Pseudomonas aeruginosa, ciprofloxacin was the most active agent tested (MIC for 90% of isolates tested, 1.0 microgram/ml). Overall, all three agents had similar activities against gram-positive organisms and were moderately active against methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci, Streptococcus species, and Enterococcus species.

In vitro antimicrobial activity of moxifloxacin compared to other quinolones against recent clinical bacterial isolates from hospitalized and community-based cancer patients.

The in vitro spectrum of moxifloxacin (a C-8-methoxyquinolone) was compared to that of ciprofloxacin and levofloxacin against 924 recent clinical isolates from cancer patients. Moxifloxacin was more active than the comparator agents against Gram-positive pathogens, with potent activity against Aerococcus spp., Listeria monocytogenes, Micrococcus spp., Rhodococcus equi, and Stomatococcus mucilaginous, methicillin-susceptible Staphylococcus spp., all beta hemolytic streptococci, viridans streptococci and Streptococcus pneumoniae. It also had good to moderate activity against Bacillus spp., Corynebacterium spp., Enterococcus faecalis, and methicillin-resistant staphylococci. Although ciprofloxacin was the most active agent tested against the Enterobacteriaceae, moxifloxacin inhibited the majority of these isolates at < or =2.0 microg/ml. Moxifloxacin was the least active of the three agents tested against Pseudomonas aeruginosa, but had significant activity against other non-fermentative Gram-negative bacilli including Acinetobacter spp., Flavobacterium spp., Pseudomonas spp. other than P. aeruginosa, and Stenotrophomonas maltophilia. The overall broad spectrum of moxifloxacin, and its availability for both oral and parenteral administration, warrants its evaluation for the prevention and treatment of infections in cancer patients.

Survey of Antibiotic Susceptibility among Gram-Negative Bacilli at a Cancer Center

A survey of the susceptibility of gram-negative bacilli isolated from cancer patients to broad-spectrum antimicrobial agents was conducted. The organisms were isolated from all patient specimens submitted to the microbiology laboratory during a 3-month study period. Overall, the least resistance was observed against cefoperazone/sulbactam, ciprofloxacin, and imipenem. Of these, cefoperazone/sulbactam has had limited usage at our institution. Drugs used more frequently (piperacillin, aztreonam, cefoperazone, ceftazidime) were associated with greater levels of resistance. Imipenem and ciprofloxacin have enjoyed wide usage but the level of resistance remains low.

Antimicrobial activity of a novel des-fluoro (6) quinolone, garenoxacin (BMS-284756), compared to other quinolones, against clinical isolates from cancer patients

The in vitro spectrum of a novel des-fluoro (6) quinolone, garenoxacin (BMS-284756), was compared with that of ciprofloxacin, levofloxacin, and trovafloxacin against 736 clinical isolates from cancer patients. Garenoxacin was the most active agent overall against Gram-positive organisms, with potent activity against Aerococcus spp., Micrococcus spp., Rhodococcus equi, Stomatococcus mucilaginous, Bacillus spp., Enterococcus faecalis, Listeria monocytogenes, methicillin-susceptible Staphylococcus spp., and all beta-hemolytic and viridans streptococci. Although ciprofloxacin was the most active agent tested against the Enterobacteriaceae garenoxacin inhibited the majority of these isolates at <or=4.0 microg/ml, its proposed susceptibility break-point. All 4 agents had sub-optimal activity against Pseudomonas aeruginosa and variable activity against other non-fermenters, with Stenotrophomonas maltophila and Alcaligenes spp. being the most resistant isolates. The overall broad spectrum of garenoxacin warrants its evaluation for the prevention or treatment of infections in cancer patients.

In vitro activities of antimicrobial agents against clinical isolates of Flavimonas oryzihabitans obtained from patients with cancer.

We evaluated the in vitro activities of 21 different antimicrobial agents against nine clinical isolates of Flavimonas oryzihabitans obtained from patients with cancer. The organisms were susceptible to most agents commonly used for the empiric therapy (aminoglycosides, ureidopenicillins, extended-spectrum cephalosporins, monobactams, and carbapenems) and prevention of infections (quinolones and trimethoprim-sulfamethoxazole) in this patient population.

In vitro antimicrobial activity of gatifloxacin compared with other quinolones against clinical isolates from cancer patients

Owing to the predominance of gram-positive pathogens in neutropenic cancer patients, newer generation quinolones with an expanded gram-positive spectrum and enhanced potency, may have a role to play for prophylaxis and/or empiric therapy in such patients. The in vitro activity of gatifloxacin was compared with that of ciprofloxacin, levofloxacin and trovafloxacin against 848 recent clinical isolates from cancer patients. Against gram-positive organisms, gatifloxacin was the most active agent tested inhibiting all Aerococcus, Listeria monocytogens, Micrococcus, Stomatococcus mucilaginous, Bacillus, and Rhodococcus equi strains at ≤2 mg/l, its designated susceptibility breakpoint. It was also very active against methicillin-susceptible staphylococci and Streptococcus spp. (including penicillin nonsusceptible Streptococcus pneumoniae and viridans streptococci). It had moderate activity against methicillin-resistant staphylococci and Enterococcus faecalis, inhibiting 68–80% of these strains at ≤2 mg/l. Gatifloxacin also had good activity against the Enterobacteriaceae (although ciprofloxacin was more potent) inhibiting >95% of isolates at ≤1 mg/l. Nonfermentative gram-negative organisms were less susceptible to all 4 agents. Gatifloxacin was very active against Acinetobacter lwoffi (MIC100 0.12 mg/l) and had moderate activity against Acinetobacter baumanii, Chryseobacterium spp., Stenotrophomonas maltophilia, Pseudomonas aeruginosa and other Pseudomonas species. Alcaligenes xylosoxidans strains were relatively resistant to all 4 agents.

Pharmacokinetics of cefoperazone in patients with neoplastic disease.

The pharmacokinetics of cefoperazone, a new semisynthetic cephalosporin, were studied in 34 patients with neoplastic disease. This compound was administered in a variety of doses and schedules without observable toxicity in any patient. The mean peak serum concentration after a 15-min intravenous infusion of 2 g was 264 microgram/ml after the first dose; the serum half-life was 2.1 h. There was no significant change in half-life or serum concentrations after 4 or 7 days of therapy. The mean peak serum concentration after infusion of 1 g over 15 min was 133 microgram/ml, with a mean of 10.7 microgram/ml at 6 h. The serum half-life was 2 h. The mean peak serum concentration after infusion of 1 g over 0.5 h was 101 microgram/ml. When 8 g was subsequently administered daily by a continuous infusion schedule, levels were maintained at 80 microgram/ml. When the dose was increased to 16 g daily, serum concentrations were maintained at an average of 153 microgram/ml. Only 37% of cefoperazone was recovered in the urine in a 12-h period after the initial dose, suggesting the importance of other mechanisms of excretion; however, serum concentrations in one patient with renal insufficiency were significantly higher than serum concentrations in patients with normal renal function.

In vitro activity of Ro 23-9424, a dual-action antibacterial agent, against bacterial isolates from cancer patients compared with those of other agents.

The in vitro activity of Ro 23-9424 against bacterial isolates from patients with cancer was compared with those of fleroxacin, ciprofloxacin, cefoperazone, and ceftazidime. Ro 23-9424 inhibited the majority of the members of the family Enterobacteriaceae and all Aeromonas isolates at a concentration of less than or equal to 1.0 micrograms/ml. It was also active against Acinetobacter spp. and Haemophilus influenzae, including beta-lactamase-producing strains. The MIC for 90% of isolates (MIC90) of Pseudomonas aeruginosa was 16.0 micrograms/ml. All group A and B streptococci were inhibited by less than or equal to 0.25 micrograms/ml, and 90% of group G streptococci and Streptococcus pneumoniae were inhibited by 1.0 micrograms/ml. All methicillin-susceptible strains of Staphylococcus aureus and 60% of methicillin-resistant strains were susceptible to 2.0 micrograms of Ro 23-9424 per ml, whereas the MIC90 for Staphylococcus epidermidis and Staphylococcus hominis isolates was 4.0 micrograms/ml. Staphylococcus haemolyticus and Enterococcus spp. were less susceptible; MIC90s for them were 16.0 and 32.0 micrograms/ml. Ro 23-9424 has a broad antibacterial spectrum and potential utility for therapy of infections in cancer patients.

Comparative in vitro activity of the new erythromycin derivative dirithromycin against gram-positive bacteria isolated from cancer patients

The in vitro activity of dirithromycin (LY-237216), a new macrolide erythromycin derivative, was compared to that of four other agents (clarithromycin, erythromycin, roxithromycin, clindamycin) against 334 gram-positive isolates obtained from cancer patients. Dirithromycin was similar in potency and antimicrobial spectrum to the other agents tested. It was very active against beta-haemolytic streptococci andStreptococcus pneumoniae, and moderately active against penicillin and methicillin susceptibleStaphylococcus aureus, Bacillus spp.,Listeria monocytogenes andCorynebacterium jeikeium. Erythromycin resistant organisms were also resistant to dirithromycin.