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Biomedical subjects

H C Neu

Publications and source records attributed to H C Neu.

At least 217 records · Page 12Linked to original sources

Ciprofloxacin disk susceptibility tests: interpretive zone size standards for 5-microgram disks.

Evaluations of 5-microgram ciprofloxacin disk diffusion susceptibility tests were performed independently by seven different investigators. The results of the separate tests were combined to increase the number of resistant strains in the challenge set of microorganisms. Based on data with 2,652 isolates, the following interpretive breakpoints are tentatively proposed for use in ongoing clinical trials of ciprofloxacin: less than or equal to 15 mm, resistant (MIC greater than 2.0 micrograms/ml); 16 to 20 mm, intermediate (1.0 less than MIC less than or equal to 2.0 micrograms/ml); and greater than or equal to 21 mm, susceptible (MIC less than or equal to 1.0 micrograms/ml). Disk tests with Streptococcus spp. and with Pseudomonas maltophilia were not reliable; other microorganisms were accurately categorized by the disk diffusion test.

Acinetobacter↗

Disk susceptibility of ofloxacin, a new carboxyquinolone.

Ofloxacin, a fluorinated carboxyquinolone, was tested against 485 clinical isolates, and the MICs and disk inhibitory zones were correlated. A critical zone of greater than or equal to 19 mm and an MIC of less than or equal to 2 micrograms/ml indicate susceptibility. An MIC of 4 micrograms/ml and a zone size of 16 to 18 mm is intermediate, and an MIC of greater than or equal to 8 micrograms/ml with a zone size of less than 15 mm indicates resistance. Alternatively, organisms inhibited by an MIC of less than or equal to 4 micrograms/ml with a critical zone diameter of greater than or equal to 15 mm could be considered susceptible. By either of these criteria, major errors in judging susceptibility or resistance are less than 1%.

Anti-Bacterial Agents↗

The pharmacology of orally administered ciprofloxacin.

Ciprofloxacin pharmacokinetics were studied in 6 volunteers after 250 and 500 mg single oral doses. Mean peak serum levels were 1.45 micrograms/ml and 2.5 micrograms/ml for 250 and 500 mg doses. The 12-h levels were 0.12 micrograms and 0.22 micrograms. T1/2 alpha values were 0.32 and 0.43 h; T1/2 beta was 4 h and Vd (area) values were 80L and 90L for the two doses respectively. AUC was 5.65 h. micrograms/ml and 10.37 h. micrograms/ml. Serum clearance was 23L for both doses. Approximately 49% of the 250 mg dose and 43% of the 500 mg dose was recovered in the urine. Ciprofloxacin's in vitro activity and human pharmacology should permit a twice or once-daily dosing schedule for systemic infections due to most Enterobacteriaceae, Haemophilus, Branhamella and Pseudomonas and S. aureus, and once-daily doses for urinary and gastrointestinal infections.

Administration, Oral↗

A perspective on the present contribution of beta-lactamases to bacterial resistance with particular reference to induction of beta-lactamase and its clinical significance.

Resistance of bacteria to beta-lactam antibiotics has become a serious problem in the past several decades. Virtually all Staphylococcus aureus, many Haemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, many Enterobacteriaceae, many Pseudomonas aeruginosa and Bacteroides species possess beta-lactamases which hydrolyze to varying degree penems, penams, carbapenems, cephems, cephamycins and monobactams. The most common plasmid-mediated beta-lactamase is the so-called TEM beta-lactamase (Richmond Sykes type IIIa) which exists in Haemophilus, Neisseria and many of the Enterobacteriaceae. Techniques to overcome this resistance have been the development of beta-lactamase stable compounds and of beta-lactamase inhibitors. However, inducible chromosomally mediated beta-lactamases in species such as Enterobacter, Pseudomonas, Citrobacter and some Serratia have become an increasing problem with more widespread use of beta-lactamase stable cephalosporins.

Anti-Bacterial Agents↗

The activity and beta-lactamase stability of cefotetan compared to other beta-lactam antibiotics.

The in vitro activity of cefotetan was assessed against beta-lactamase producing clinical isolates. The majority of Enterobacteriaceae were inhibited by less than or equal to 8 micrograms/ml with 50% of isolates inhibited by less than or equal to 1 microgram/ml. Cefotetan inhibited organisms resistant to cefazolin, cefonicid and cefoperazone, but not isolates of Enterobacter, Citrobacter or Serratia resistant to ceftizoxime. Cefotetan inhibited beta-lactamase producing Haemophilus influenzae and Neisseria gonorrhoeae at less than or equal to 1 microgram/ml, but it did not inhibit Acinetobacter or Pseudomonas aeruginosa. Cefotetan was as active as cefoxitin against anaerobic species such as Bacteroides fragilis and Clostridium. Cefotetan was not hydrolyzed by Richmond-Sykes plasmid beta-lactamases of type III such as TEM and SHV, nor by the OXA or PSE beta-lactamases. It also was not hydrolyzed by cephalosporinases of Richmond-Sykes type Ia or Id. Cefotetan inhibited beta-lactamases of the type Ia and Id, but it also induced these beta-lactamases in P. aeruginosa, E. cloacae and C. freundii.

Bacteria↗

The activity of cefbuperazone, a 7 alpha-methoxy 7 beta acyl ureido cephalosporin.

The activity of cefbuperazone, a 7 alpha-methoxy ureido cephalosporin, was determined against 726 clinical isolates. Ninety percent of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter diversus, Proteus mirabilis, Enterobacter aerogenes, Proteus vulgaris, Morganella morganii, Salmonella, and Shigella species were inhibited by less than or equal to 6.3 micrograms/ml. Cefbuperazone was more active than cefamandole, cefoxitin and piperacillin against these species. Concentrations of 25 micrograms/ml of cefbuperazone were needed to inhibit Serratia marcescens and Providencia species, and 50% of Enterobacter cloacae had MICs greater than 25 micrograms/ml. Cefbuperazone was less active by 8 to 32-fold than cefotaxime or moxalactam against most Enterobacteriaceae. Cefbuperazone did not inhibit Acinetobacter or Pseudomonas species. Hemolytic streptococci were inhibited by 12.5 micrograms/ml and staphylococci by 25 micrograms/ml. Cefbuperazone had activity comparable to cefoxitin and moxalactam against Bacteroides fragilis with MIC90s of 6.3 micrograms/ml. Cefbuperazone was not hydrolyzed by plasmid or chromosomal beta-lactamases and was an inhibitor of the P99 E. cloacae beta-lactamase with an I50 of 1 microgram/ml. It was a less effective inhibitor of the K. oxytoca K1 and E. coli TEM-1 beta-lactamases than was clavulanic acid. Cefbuperazone induced beta-lactamases in P. aeruginosa and resistant E. cloacae. A permeability barrier in E. cloacae, C. freundii and P. aeruginosa is suggested by the potentiation of cefbuperazone's activity by EDTA.

Bacteria↗

Ceftriaxone in the treatment of serious infections, particularly after surgery.

The clinical efficacy and safety of ceftriaxone when administered twice daily was evaluated in the treatment of serious infections, including 9 episodes of bacteremia, 4 of pneumonia, 7 of intra-abdominal or soft tissue infections, 11 of urinary tract infections, 3 of osteomyelitis, and 5 of meningitis. Causative pathogens were Strep. pneumoniae, other hemolytic streptococci, E. coli, P. mirabilis, K. pneumoniae, and species of Enterobacter, Serratia, and Pseudomonas. The overall clinical cure rate was 87 percent and the bacteriologic cure rate was 77 percent. Cures were achieved in infections due to organisms resistant to ampicillin, cefazolin, cefamandole, carbenicillin, and gentamicin. Peak plasma levels were far in excess of the minimal inhibitory concentrations of Enterobacteriaceae. Adverse effects were infrequent, and in only one instance was it necessary to discontinue treatment. Resistance to ceftriaxone developed during therapy with several Enterobacter and Pseudomonas species isolates. Ceftriaxone appears to be a useful agent for treatment of serious gram-negative infections in seriously ill patients.

Abdomen↗

Pharmacokinetics of ceftriaxone after intravenous infusion and intramuscular injection.

The pharmacokinetics of ceftriaxone were evaluated in eight adults after doses of 1 g administered by intravenous infusion and 1 and 0.5 g administered by intramuscular injection. Mean peak plasma concentrations were 168 micrograms/ml for 1 g given intravenously, 81 micrograms/ml for 1 g given intramuscularly, and 46 micrograms/ml for 0.5 g intramuscularly. Plasma concentrations were similar by both high pressure liquid chromatographic and microbiologic methods. The plasma half-lives were 7.6 and 8.3 hours, respectively, for the intravenous infusion and intramuscular injection. Plasma concentrations were equal for the 1 g intravenous and intramuscular routes by 2.5 hours. Plasma concentrations exceeded the minimal inhibitory concentrations (MICs) of most aerobic gram-positive and gram-negative organisms with the exception of Pseudomonas aeruginosa and Acinetobacter species for 24 hours. Urinary concentrations exceeded 100 micrograms/ml for 24 hours for the 1-g doses and for 12 hours for the 0.5-g dose. Urinary recovery of ceftriaxone within 24 hours was 40 percent for intravenous infusion and 33 and 34 percent for the intramuscular injection. A single 1-g dose daily will exceed the MICs of most staphylococcal and streptococcal species and Enterobacteriaceae for 12 to 24 hours.

Adult↗

Changing patterns of hospital infections: implications for therapy. Changing mechanisms of bacterial resistance.

During the past decade there has been a marked increase in resistance of bacteria to antimicrobial agents. Microorganisms have developed the ability to make altered receptors for antimicrobial agents, have prevented agents from reaching their receptors within the bacterial cell, now have enzymes to destroy antibiotics, and have resistant metabolic pathways. Altered penicillin receptors, penicillin-binding proteins, have been found in Streptococcus pneumoniae, Streptococcus faecalis, Staphylococcus aureus, Neisseria gonorrhoeae, Clostridium, and Pseudomonas aeruginosa. Resistance based on decreased entry of drugs has been found for penicillins, cephalosporins, aminoglycosides, and tetracyclines in the Enterobacteriaceae and Pseudomonas aeruginosa. Beta-lactamase resistance has increased significantly being encountered in Neisseria, Haemophilus, Enterobacteriaceae, and Pseudomonas species. Chromosomal inducible beta-lactamases, which function as cephalosporinases, have been a particular problem in Enterobacter and Citrobacter species, and organisms resistant to the third-generation cephalosporins have been isolated from patients. It is clear that beta-lactamases and changes in cell wall permeability will play an extremely important role in the future of the new penicillins and cephalosporins.

Anti-Bacterial Agents↗

Current mechanisms of resistance to antimicrobial agents in microorganisms causing infection in the patient at risk for infection.

The mechanisms of resistance encountered in bacteria causing infection in the patient at risk for infection are diverse. Most resistance currently seen is the result of plasmid transfer rather than mutational events. However, extensive use of antimicrobial agents in the hospital has caused the selection of organisms resistant to many agents by virtue of chromosomally mediated mechanisms. Staphylococcus aureus resistant to beta-lactams due to altered penicillin-binding proteins has become a problem in certain patients such as narcotic addicts and chronic care facility patients exposed to many beta-lactam antibiotics. S. epidermidis has also proved to be a problem in patients with indwelling foreign devices, and altered penicillin-binding proteins also make these organisms resistant to available penicillins and cephalosporins. Streptococcus fecalis has become increasingly resistant to aminoglycosides, erythromycin, and tetracyclines due to plasmid-mediated enzymes. Hemophilus influenzae resistant to both penicillins and chloramphenicol by virtue of beta-lactamases and chloramphenicol transacetylase has been encountered. Beta-lactamase-mediated resistance of Enterobacteriaceae, Escherichia coli, and Klebsiella pneumoniae to beta-lactam antibiotics has increased, and resistance of Serratia marcescens and Pseudomonas aeruginosa to aminoglycosides and penicillins is a widespread phenomenon. Mechanisms to reduce resistance will include not only careful attention to hygienic practices but also more appropriate use of antibiotics selecting the proper agent depending on the type of patient and environment in which the infection develops.

Anti-Bacterial Agents↗

Clinical efficacy of ceftazidime. Treatment of serious infection due to multiresistant Pseudomonas and other gram-negative bacteria.

Ceftazidime, a beta-lactamase stable cephalosporin, was administered to 57 patients. Substantial underlying disease was present in the majority of patients, and 50% were in critical or poor condition. Ceftazidime inhibited all initial isolates of Enterobacteriaceae at 8 mg/L or less, regardless of resistance to other antibiotics and the majority of Pseudomonas aeruginosa at 12 mg/L or less. The mean serum level after infusion of 1 g during 30 minutes was 62 mg/L. Overall clinical response was 84%, and the bacteriological response was 72% excluding cystic fibrosis patients. No major adverse effects were encountered. Resistance developed in Pseudomonas from patients with cystic fibrosis and in Enterobacter from two other patients. Ceftazidime was an effective, safe therapy for serious infection due to multiply resistant Pseudomonas and other aerobic gram-negative bacilli including aminoglycoside-resistant Serratia and Klebsiella.

Acute Disease↗

Pyridinium 2-azo-p-dimethylaniline chromophore, a chromogenic reagent for beta-lactamase testing compared to nitrocefin.

Pyridinium-2-azo-p-dimethylaniline chromophore was evaluated as a test tube, filter paper and spectrophotometric assay for detection of beta-lactamases from gram-positive and gram-negative organisms. Although useful for detection of TEM beta-lactamases in Haemophilus influenzae and Neisseria gonorrhoeae, it was a poor agent for detecting TEM, OXA and PSE enzymes in Enterobacteriaceae. It also proved poor for detecting cephalosporinases in Pseudomonas aeruginosa and Enterobacteriaceae, and penicillinases in Staphylococcus aureus when compared to nitrocefin. As a spectrophotometric substrate it was equivalent to nitrocefin and cephaloridine with various beta-lactamases.

Anti-Bacterial Agents↗

Thrombocytosis: an acute-phase reactant, not an adverse reaction to the new beta-lactam antibiotics.

Thrombocytosis has been described as an adverse drug reaction in up to 30% of patients treated with new beta-lactam antibiotics. We evaluated 350 patients with acute noninfectious conditions and infectious diseases treated with a variety of new and old agents. Results indicate that thrombocytosis is an acute-phase reactant and not an adverse reaction to any antimicrobial agent.

Anti-Bacterial Agents↗

Do we need the third-generation cephalosporins?

Third-generation cephalosporins have been available for the past 5 years. The continued increase in resistance of bacteria to older antimicrobial agents and the safety profile of a number of the third-generation agents have established situations in which these compounds are useful. Upper respiratory infections such as epiglottitis, lower respiratory tract infections due to Enterobacteriaceae are examples of illnesses in which third-generation cephalosporins would be preferred to older drug programmes. Bone and joint infections due to Enterobacteriaceae can be treated with third-generation cephalosporins with less risk of toxicity than that associated with aminoglycoside use. But this is an area in which resistance may develop. Meningitis in the elderly due to Escherichia coli or Klebsiella pneumoniae are best treated with cefotaxime and the third-generation cephalosporins are alternative therapy for neonatal and the other forms of meningitis except Listeria or Pseudomonas. These drugs have proved extremely useful in treatment of penicillinase-producing Neisseria gonorrhoeae. Hospital-acquired urinary tract infections in the elderly can be treated with these agents since they provide excellent urinary levels and have a low risk of nephrotoxicity. The need for third-generation cephalosporins in gynaecological and intra-abdomonal infections is less clear. Selected patients will benefit from their use. Closer attention to the excellent in vitro activity and pharmacological activity of third-generation cephalosporins should establish other areas of need for these compounds, but it will be necessary to follow closely the development of resistance to these compounds since species such as Enterobacter, Serratia and Citrobacter can become resistant.

Abdomen↗

Ciprofloxacin, a quinolone carboxylic acid compound active against aerobic and anaerobic bacteria.

The in vitro activity of ciprofloxacin, a quinolone-carboxylic acid derivative, was compared with those of norfloxacin, cefotaxime, cephalexin, ceftazidime, moxalactam, amoxicillin, and methicillin and other agents, as appropriate. The MICs of ciprofloxacin for 90% of members of the family Enterobacteriaceae and for Pseudomonas aeruginosa, Neisseria spp., and Bacteroides fragilis were between 0.005 and 0.8 micrograms/ml, whereas streptococci and staphylococci were all inhibited by less than or equal to 6.3 micrograms/ml. Ciprofloxacin was 4- to 32-fold more active than norfloxacin and inhibited gentamicin-, ameikacin-, cefotaxime-, and moxalactam-resistant members of the family Enterobacteriaceae and P. aeruginosa and methicillin-resistant Staphylococcus aureus. The activity of ciprofloxacin was not affected by serum but decreased in the presence of acid urine. The frequency of resistance to ciprofloxacin was between 10(-7) and 10(-9).

Anti-Bacterial Agents↗

In vitro comparison of the activity of RU 28965, a new macrolide, with that of erythromycin against aerobic and anaerobic bacteria.

RU 28965, a novel macrolide antibiotic, inhibited most gram-positive species at concentrations similar to that of erythromycin but was not active, even at alkaline pH, against Pseudomonas spp. or members of the family Enterobacteriaceae. Staphylococci and streptococci resistant to erythromycin were resistant to RU 28965. RU 28965 inhibited Haemophilus influenzae, including a number of beta-lactamase, ampicillin-resistant isolates, and Neisseria meningitidis and Neisseria gonorrhoeae at concentrations similar to those of erythromycin. Against anaerobic species, Bacteroides fragilis and Clostridia and Fusobacterium spp., RU 28965 was less active than erythromycin, but its activity against Campylobacter and Legionella spp. was similar to that of erythromycin.

Anti-Bacterial Agents↗