Effect of 5-fluorouracil, mitoxantrone, methotrexate, and vincristine on the antibacterial activity of ceftriaxone, ceftazidime, cefotiam, piperacillin, and netilmicin

Using the checkerboard agar dilution technique, antibacterial activity and in vitro interactions of 4 antineoplastic agents and 5 antimicrobial drugs were examined against 56 strains of 7 bacterial species. 5-fluorouracil was found to inhibit all strains of Staphylococcus aureus and of Staphylococcus epidermidis at a concentration of 0.8 micrograms/ml or less. 84% of all gram-negative strains were inhibited synergistically when 5-fluorouracil was combined with beta-lactam antibiotics. Methotrexate and cefotiam were antagonistic in 42% of all combinations, especially when tested against Escherichia coli and Klebsiella pneumoniae.     

Susceptibilities of non-Pseudomonas aeruginosa gram-negative nonfermentative rods to ciprofloxacin, ofloxacin, levofloxacin, D-ofloxacin, sparfloxacin, ceftazidime, piperacillin, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, and imipenem.

Agar dilution MICs of 10 agents against 410 non-Pseudomonas aeruginosa gram-negative nonfermentative rods were determined. MICs at which 50 and 90% of the isolates were inhibited, respectively, were as follows (in micrograms per milliliter): sparfloxacin, 0.5 and 8.0; levofloxacin, 1.0 and 8.0; ciprofloxacin, 2.0 and 32.0; ofloxacin, 2.0 and 32.0; D-ofloxacin, 32.0 and > 64.0; ceftazidime, 8.0 and 64.0; piperacillin with or without tazobactam, 16.0 and > 64.0; trimethoprim-sulfamethoxazole, 0.5 and > 64.0; imipenem, 2.0 and > 64.0. With the exception of those for Stenotrophomonas maltophilia, Burkholderia cepacia, and Alcaligenes faecalis-A. odorans, agar dilution MICs for all strains tested were within 1 dilution of inhibitory (bacteriostatic) levels as determined by time-kill methodology.     

Comparative ototoxicity of ribostamycin, dactimicin, dibekacin, kanamycin, amikacin, tobramycin, gentamicin, sisomicin and netilmicin in the inner ear of guinea pigs

Nine aminoglycoside antibiotics, ribostamycin (RSM), dactimicin (DAC), dibekacin (DKB), kanamycin (KM), amikacin (AMK), netilmicin (NTL), tobramycin (TOB), gentamicin (GM) and sisomicin (SISO) were administered intramuscularly to guinea pigs for 4 weeks, and ototoxicity and drug concentration in the inner ear fluid were determined. RSM and DAC showed the weakest ototoxicity against the cochlea and vestibular organs. AMK and KM were more toxic to cochlea than vestibular organs. DKB, TOM, GM and SISO were equally toxic to vestibular organs and cochlea. NTL was more toxic to vestibular organs than cochlea. As judged from the pinna reflex response and hair cell damage in the cochlea, the order of auditory toxicity was the following: SISO greater than GM greater than TOB greater than AMK greater than DKB greater than KM greater than NTL, DAC RSM, whereas the vestibular toxicity was in the following order: SISO greater than GM greater than DKB greater than TOB greater than NTL greater than AMK greater than KM greater than DAC, RSM. RSM, causing the weakest ototoxicity, showed a low drug concentration in the inner ear fluid, while GM, causing severe ototoxicity, showed the highest drug level under the same conditions.     

Reviews of books, videos, CDs, audiotapes, web sites, and more, written by emergency nurses

Zimmermann PG. Philadelphia: Hanley & Belfus, 2002, 243 pp, ISBN 1-56053-529-6.     

In vitro activity of piperacillin, ticarcillin, mezlocillin, ticarcillin-clavulanic acid, aztreonam, ceftazidime, azlocillin, cefoperazone, and thienamycin against Pseudomonas aeruginosa

The in vitro susceptibility of 103 well-characterized strains of Pseudomonas aeruginosa to nine antimicrobial agents was assessed by means of the Kirby-Bauer disk diffusion assay and the microtiter minimal inhibitory concentration assay. The antimicrobials, from the most to the least active against P aeruginosa, were thienamycin greater than ceftazidime greater than piperacillin greater than azlocillin greater than cefoperazone greater than aztreonam greater than ticarcillin greater than ticarcillin-clavulanic acid greater than mezlocillin. The resistance patterns of the antimicrobial agents suggest that P aeruginosa resistant to a penicillin, cephalosporin, or aztreonam may be susceptible to thienamycin.     

Absorption, distribution, metabolic fate, and elimination of pefloxacin mesylate in mice, rats, dogs, monkeys, and humans

Pefloxacin mesylate is well absorbed by the oral route. The antimicrobial activity in dog, cynomolgus monkey, and human plasma was essentially due to unchanged drug which respectively accounted for 64, 94, and 84% of the total activity (ratios derived from relative area under the curve [AUC] values). Half-lives ranged from 1.9 h in mice to 8.6 h in humans. Protein binding was weak, about 20% in plasma. Except in brain, concentrations in most of the organs and tissues tested in rats and dogs were higher than the plasma levels. Microbiological activity in urine was mainly due to pefloxacin and norfloxacin, the N-desmethyl metabolite. The norfloxacin/pefloxacin ratios were 0 in mice, ca. 1 in rats and dogs, 1.6 in cynomolgus monkeys, and 2.3 in humans. The principal urinary compounds were unchanged drug in mice, pefloxacin glucuronide and pefloxacin N-oxide in rats and dogs, norfloxacin and pefloxacin in monkeys, and pefloxacin N-oxide and norfloxacin in humans. The urinary recovery of identified metabolites was 29.5% of the dose in mice, 37.8% in rats, 36.3% in dogs, 26.5% in monkeys, and 58.9% in humans. Biliary excretion occurred and was extensive in rats and dogs, mainly as a glucuronide conjugate of the drug. In rat and human bile, the main active compound was unchanged pefloxacin.     

Aluminum, iron, lead, cadmium, copper, zinc, chromium, magnesium, strontium, and calcium content in bone of end-stage renal failure patients.

BACKGROUND: Little is known about trace metal alterations in the bones of dialysis patients or whether particular types of renal osteodystrophy are associated with either increased or decreased skeletal concentrations of trace elements. Because these patients are at risk for alterations of trace elements as well as for morbidity from skeletal disorders, we measured trace elements in bone of patients with end-stage renal disease. METHODS: We analyzed bone biopsies of 100 end-stage renal failure patients enrolled in a hemodialysis program. The trace metal contents of bone biopsies with histological features of either osteomalacia, adynamic bone disease, mixed lesion, normal histology, or hyperparathyroidism were compared with each other and with the trace metal contents of bone of subjects with normal renal function. Trace metals were measured by atomic absorption spectrometry. RESULTS: The concentrations of aluminum, chromium, and cadmium were increased in bone of end-stage renal failure patients. Comparing the trace metal/calcium ratio, significantly higher values were found for the bone chromium/calcium, aluminum/calcium, zinc/calcium, magnesium/calcium, and strontium/calcium ratios. Among types of renal osteodystrophy, increased bone aluminum, lead, and strontium concentrations and strontium/calcium and aluminum/calcium ratios were found in dialysis patients with osteomalacia vs the other types of renal osteodystrophy considered as one group. Moreover, the concentrations of several trace elements in bone were significantly correlated with each other. Bone aluminum was correlated with the time on dialysis, whereas bone iron, aluminum, magnesium, and strontium tended to be associated with patient age. Bone trace metal concentrations did not depend on vitamin D intake nor on the patients' gender. CONCLUSIONS: The concentration of several trace elements in bone of end-stage renal failure patients is disturbed, and some of the trace metals under study might share pathways of absorption, distribution, and accumulation. The clinical significance of the increased/decreased concentrations of several trace elements other than aluminum in bone of dialysis patients deserves further investigation.     

The Hereditary Syndrome of Thrombocytopathia, Bleeding Tendency, Extreme Miosis, Muscular Fatigue, Asplenia, Headache, etc

SYNOPSIS
A new, autosomal dominantly inherited syndrome with a bleeding disorder was described in 1985 by Stormorken and his co-workers.1,2 In this multifaceted syndrome, there were the following integral components: thrombocytopathia, extreme miosis with Argyll Robertson-like traits, muscular fatigue, a tendency to spasms, asplenia, ichthyosis, dyslexia, etc.
Headache with migraine traits was also present in the family in all 4 generations in which this syndrome had been observed. Nasal and conjunctival bleeding were part of the headache picture in some of the individuals exhibiting the hemorrhagic syndrome. While the attack-related bleeding disturbances only involved family members who also suffered from the hemorrhagic syndrome, the headache per se may seem to behave differently: The affected son's headache seems to have developed into a headache with tension headache traits, whereas the other, unaffected, son's headache has common migraine traits. The familial headache which in earlier generations clearly had migraine traits, therefore, may be inherited independently from the hemorrhagic disorder. In other words, a migraine or migraine-like headache is most probably not an obligatory integral part of this syndrome. The thrombocytopathia in this disorder comprises abnormal serotonin storage, uptake, and release (Stormorken and co-workers, to be published).
The admittedly somewhat farfetched possibility also exists that the headache, although being similar to migraine, differs essentially from it and may be an expression of the serotonin aberration.     

Comparative in vitro activities of XRP 2868, pristinamycin, quinupristin-dalfopristin, vancomycin, daptomycin, linezolid, clarithromycin, telithromycin, clindamycin, and ampicillin against anaerobic gram-positive species, actinomycetes, and lactobacilli

A comparative study of the in vitro activities of XRP 2868, a new oral streptogramin, against 266 anaerobic gram-positive clinical isolates using the agar dilution method showed that the XRP 2868 MICs for 95% (254 of 266) of isolates were < or =0.5 microg/ml. XRP 2868 MICs for only two strains, one being Clostridium clostridioforme (MIC, 16 microg/ml) and the other being Clostridium difficile (MIC, 32 microg/ml), were >2 microg/ml. Depending on its pharmacokinetics and pharmacodynamics, XRP 2868 has potential for use against infections with gram-positive anaerobes and deserves further clinical evaluation.     

Activity of WY-49605 compared with those of amoxicillin, amoxicillin-clavulanate, imipenem, ciprofloxacin, cefaclor, cefpodoxime, cefuroxime, clindamycin, and metronidazole against 384 anaerobic bacteria.

The National Committee for Clinical Laboratory Standards agar dilution method was used to compare the in vitro activity of WY-49605 (also called SUN/SY 5555 and ALP-201), a new broad-spectrum oral penem, to those of amoxicillin, amoxicillin-clavulanate, imipenem, ciprofloxacin, cefaclor, cefpodoxime, cefuroxime, clindamycin, and metronidazole against 384 clinically isolated anaerobes. These anaerobic organisms included 90 strains from the Bacteroides fragilis group, 87 Prevotella and Porphyromonas strains, non-B. fragilis group Bacteroides strains, 56 fusobacteria, 55 peptostreptococci, 49 gram-positive non-spore-forming rods, and 47 clostridia. Overall, WY-49605 had an MIC range of 0.015 to 8.0 micrograms/ml, an MIC at which 50% of the isolates are inhibited (MIC50) of 0.25 microgram/ml, and an MIC at which 90% of the isolates are inhibited (MIC90) of 2.0 micrograms/ml. Good activity against all anaerobe groups was observed, except for Clostridium difficile and lactobacilli (MIC50s of 4.0 and 2.0 micrograms/ml, respectively, and MIC90s of 8.0 and 2.0 micrograms/ml, respectively). Imipenem had an MIC50 of 0.03 microgram/ml and an MIC90 of 0.25 microgram/ml. Ciprofloxacin was much less active (MIC50 of 2.0 micrograms/ml and MIC90 of 16.0 micrograms/ml). By comparison, all oral beta-lactams were less active than WY-49605, with susceptibilities as follows: amoxicillin MIC50 of 8.0 micrograms/ml and MIC90 of > 256.0 micrograms/ml), amoxicillin-clavulanate MIC50 of 1.0 microgram/ml and MIC90 of 8.0 micrograms/ml, cefaclor MIC50 of 8.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml, cefpodoxime MIC50 of 4.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml, and cefuroxime MIC50 of 4.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml. Clindamycin was active against all groups except some members of the B. fragilis group, Fusobacterium varium, and some clostridia ( overall MIC50 of 0.5 micrograms/ml and overall MIC90 of 8.0 micrograms/ml). Metronidazole was active (MIC of less than or equal to 4.0 micrograms/ml) against all gram-negative anaerobic rods, but most gram-positive non-spore-forming rods, some peptostreptococci, and some clostridia were less susceptible. To date, WY-49605 is the most active oral beta-lactam against anaerobes: these results suggest clinical evaluation for clinical indications suitable for oral therapy.