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Biomedical subjects

H C Neu

Publications and source records attributed to H C Neu.

At least 523 records · Page 29Linked to original sources
PubMedDate not supplied

Comparative studies of cefoxitin and cephalothin: an overview.

A comparative study of the efficacy and safety of cefoxitin and cephalothin in the treatment of serious infections was carried out by 21 investigators. A total of 320 patients were treated with cefoxitin, and 276 patients were treated with cephalothin. In each group 50% of patients could be evaluated. Patients were randomly allocated to groups in open fashion, and final analysis showed that the groups were comparable in terms of sex, age, severity of illness, and duration of therapy. The majority of pathogens isolated were susceptible to both agents, although 13% of gram-negative bacilli and anaerobes were susceptible to cefoxitin alone. The overall percentage of patients cured or improved by cephalothin was 93%; for cefoxitin the proportion was 91%. No statistical differences in response by type of organism or site of infection were shown. Cefoxitin was effective in treating infections and in eradicating the pathogenic bacteria. Cefoxitin was as well tolerated as cephalothin and produced no more adverse reactions or abnormal laboratory findings than did cephalothin. The results of this study demonstrate that cefoxitin is as effective in achieving bacteriologic and clinical cures as is cephalothin and also is effective in treatment of infections due to cephalothin-resistant bacteria.

Bacterial Infections↗
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Cefoxitin: an overview of clinical studies in the United States.

Cefoxitin, a new cephamycin antibiotic that is active against aerobic and anaerobic bacteria, was studied by 35 investigators in the United States. Of 657 patients eligible for evaluation of efficacy of the compound, 69% were cured and 92% were cured or improved on clinical grounds. Bacteriologic response to therapy with cefoxitin was equally good for infections due to gram-positive cocci (94% cured), gram-negative bacilli (87% cured), and anaerobes (95% cured). Cefoxitin was effective clinically and bacteriologically in the eradication of infections due to organisms resistant to ampicillin, cephalothin, chloramphenicol, tetracycline, and aminoglycosides. Overall rates of favorable response to cefoxitin therapy by disease were: lower respiratory tract infections, 90%; urinary tract infections, 87%; intraabdominal infections, 90%; gynecologic infections, 94%; and septicemia, 84%. Cefoxitin was tolerated well, and major abnormalities of hematologic, hepatic, renal, or central nervous system function were encountered rarely. Resistance to cefoxitin did not develop among gram-negative cocci, anaerobes, or gram-negative bacilli in the medical centers in which the antibiotic was used.

Bacterial Infections↗
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Bacterial resistance to fluoroquinolones.

Fluoroquinolones inhibit bacteria by interacting with the A subunit of DNA gyrase. Resistance to older agents such as nalidixic acid was due to mutations in the gyrA gene. Resistance to the new fluoroquinolones (e.g., norfloxacin, enoxacin, ofloxacin, pefloxacin, and ciprofloxacin) as a consequence of spontaneous single-step mutation occurs at a low frequency, less than 10(-9), and generally results in a 300-fold lower level of resistance than does the mutation to nalidixic acid resistance. High-level resistance to quinolones can be produced by serial exposure of bacteria to subinhibitory concentrations. Cross-resistance to all quinolones usually occurs. High-level resistance appears to be due to alterations in the A subunit of DNA gyrase and in a simultaneous alteration in permeability that probably is related to a loss of outer-membrane proteins. Organisms resistant to the new quinolones may also be resistant to other antibiotic classes, including beta-lactams. Clinical resistance to the new quinolones has been uncommon and has occurred most often among respiratory pathogens, particularly Pseudomonas aeruginosa from patients with cystic fibrosis and, less frequently, among strains of Serratia marcescens, P. aeruginosa, and Staphylococcus aureus from wound infections. Resistance of urinary or diarrheal isolates has been rare. So far, overall resistance of bacteria to quinolones has not emerged as a major problem, but--like resistance to all other antimicrobial classes--does occur in certain clinical settings.

Anti-Bacterial Agents↗
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Synergy of fluoroquinolones with other antimicrobial agents.

Synergy resulting from the combination of ciprofloxacin and an antipseudomonal penicillin has been reported for 20%-50% of isolates of Pseudomonas aeruginosa. A similar effect has also been reported for the combination of ciprofloxacin and fosfomycin. In contrast, the combination of quinolones and aminoglycosides rarely showed synergy when tested against P. aeruginosa. Most studies have shown that the combination of beta-lactams or aminoglycosides with quinolones is indifferent against Escherichia coli, Klebsiella species, Enterobacter species, Citrobacter species, and Serratia species. The combination of ciprofloxacin and chloramphenicol can be antagonistic against E. coli. In general, the combination of quinolone antibiotics with other drugs tested against staphylococci, enterococci, and anaerobic species has shown indifference. The neutropenic mouse model of infection has demonstrated the synergistic effect of ciprofloxacin plus antipseudomonal penicillins; the combination of ciprofloxacin and rifampin has been superior to single agents in experimental Staphylococcus aureus osteomyelitis. Ciprofloxacin has been the quinolone studied most thoroughly, and few data are available about the combination of other quinolones with other antimicrobial agents. Overall, the occurrence of synergy when quinolones are combined with other antimicrobial agents is infrequent, and clinical studies that demonstrate the clinical relevance of data from in vitro and animal models of infection are not available. However, data from in vitro and animal model studies indicate that the combination of a quinolone with other antimicrobial agents rarely results in antagonism.

4-Quinolones↗
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The pharmacokinetics of bacampicillin.

Bacampicillin is an ethoxycarbonyloxyethyl ester of ampicillin that is rapidly converted to free ampicillin, the active agent, by nonspecific esterases present in serum and in the intestinal wall. The compound is absorbed more rapidly than ampicillin, with peak absorption occurring 45 min to 1 hr after administration of the drug, whereas the peak after administration of the parent compound is at 2 hr. Peak levels of drug in serum after a 400-mg dose of bacampicillin (molar equivalent, 278 mg of ampicillin) are 6-8 micrograms/ml. Peak levels after an 800-mg dose of bacampicillin (molar equivalent, 556 mg of ampicillin) are 11-14 micrograms/ml. These peak levels are twofold greater than those achieved with equimolar doses of ampicillin. Ingestion of bacampicillin with food does not decrease or delay absorption of the drug. Recovery of ampicillin in urine after ingestion of bacampicillin is 75% vs. a recovery of 45% after ampicillin. Ampicillin appears earlier in tears, saliva, bronchial and maxillary sinus secretions, middle ear fluid, skin blisters. lymph, and urethral and cervical secretions, and the levels obtained in these tissues are greater after ingestion of bacampicillin than after ampicillin. The pharmacokinetics of bacampicillin and ampicillin in the period 2.5-8 hr after their ingestion is virtually identical at equimolar doses.

Ampicillin↗
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Current practices in antimicrobial dosing.

There has been minimal utilization of pharmacologic principles in the establishment of treatment programs for many infectious diseases. Drugs with markedly different half-lives and peak levels in serum have been prescribed at the same dosage intervals. No attempt has been made to determine if the efficacy of dosing programs in which levels in serum that exceed bactericidal levels are achieved but in which doses are administered infrequently is greater than or equal to that of current programs. Double-blind studies of therapeutic programs in which drugs with different pharmacokinetic properties are compared are the only means of eliminating the current confusion regarding dosing practices.

Animals↗
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Trimethoprim alone for treatment of urinary tract infection.

Studies of the use of trimethoprim (TMP) alone compared with the use of trimethoprim and sulfamethoxazole in combination (TMP-SMZ) have shown that TMP alone is as effective as TMP-SMZ in the treatment of urinary tract infections. With the exception of one study in which use of TMP singly for 28 days for treatment of recurrent urinary tract infections selected resistant nonfermenting bacteria, the use of TMP singly for treatment of urinary tract infections has not resulted in selection of resistant Enterobacteriaceae. However, use of both TMP and TMP-SMZ for prevention of traveler's diarrhea has resulted in plasmid mediated resistance in Escherichia coli.

Chronic Disease↗
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Mechanisms of bacterial resistance to antimicrobial agents, with particular reference to cefotaxime and other beta-lactam compounds.

Many mechanisms exist by which bacteria can become resistant to antimicrobial agents. Although mutational events are important in the development of resistance to some agents, by far the most important factor in resistance is extrachromosomal genetic material in the form of plasmids. Important mechanisms of bacterial resistance to antibiotics are interference with the transport of the antimicrobial agents into the bacterial cell, inactivation of the agent, and alteration of the target site or metabolic pathway by the microorganism. In order to affect bacteria, beta-lactam antibiotics must pass through proteins at the surface of the cell, must evade destruction by beta-lactamases, and must have an affinity for proteins involved in cell wall synthesis. A number of the new beta-lactam antibiotics, because of their great resistance to destruction by beta-lactamases and their high affinity for penicillin-binding proteins, have overcome many of the mechanisms bacteria have used in the past to resist beta-lactam drugs.

Anti-Bacterial Agents↗
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Antibacterial activity of desacetylcefotaxime alone and in combination with cefotaxime.

Cefotaxime is metabolized to 3-desacetylcefotaxime. The antibacterial activity of desacetylcefotaxime is four- to eightfold less than that of cefotaxime. The activity of desacetylcefotaxime is species- and strain-specific. Although desacetylcefotaxime is less active than cefotaxime, it is more active than cefazolin, cefamandole, or cefoxitin. Desacetylcefotaxime does not inhibit many strains of Morganella, most strains of Pseudomonas aeruginosa, some strains of Serratia marcescens, some strains of Providencia, and many strains of Bacteroides fragilis at clinically achievable concentrations. Cefotaxime and desacetylcefotaxime act synergistically against 72% of strains tested, and antagonism between the two compounds is seen only with strains of Morganella and Proteus vulgaris. The presence of the metabolite desacetylcefotaxime increases rather than decreases the activity of cefotaxime.

Anti-Bacterial Agents↗
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The emergence of bacterial resistance and its influence on empiric therapy.

The discovery of antimicrobial agents had a major impact on the rate of survival from infections. However, the changing patterns of antimicrobial resistance caused a demand for new antibacterial agents. Within a few years of the introduction of penicillin, the majority of staphylococci were resistant to that drug. In the 1960s the production of the semisynthetic penicillins provided an answer to the problem of staphylococcal resistance. In the early 1960s most Escherichia coli were susceptible to the new beta-lactam antibiotic ampicillin; by the end of that decade, plasmid-mediated beta-lactamase resistance was found in 30%-50% of hospital-acquired E. coli. Use of certain agents resulted in the selection of bacteria, such as Klebsiella, that are intrinsically resistant to ampicillin. The original cephalosporins were stable to beta-lactamase, but the use of these agents was in part responsible for the appearance of infections due to Enterobacter species, Citrobacter species, and Pseudomonas aeruginosa. These bacteria, as well as Serratia, were resistant to many of the available beta-lactam agents. Aminoglycosides initially provided excellent activity against most of the facultative gram-negative bacteria. However, the widespread dissemination of the genes that cause production of the aminoglycoside-inactivating enzymes altered the use of those agents. Clearly, the evolution of bacterial resistance has altered the prescribing patterns for antimicrobial agents. Knowledge that beta-lactam resistance to ampicillin or cephalothin is prevalent is causing physicians to select as empiric therapy either a combination of two or more agents or agents to which resistance is uncommon. The new cephalosporins offer a broad spectrum of anti-bacterial activity coupled with low toxicity. However, physicians must closely follow the changing ecology of bacteria when these agents are used, because cephalosporins can also select bacteria resistant to themselves and thereby abolish their value as empiric therapy.

Aminoglycosides↗
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Activity of cefsulodin and other agents against Pseudomonas aeruginosa.

Cefsulodin is a novel cephalosporin that contains a pyridinomethyl substituent at position 3 of the dihydrothiazine ring and a sulfo group on the acyl side chain. Cefsulodin has a high affinity for penicillin-binding proteins of Pseudomonas aeruginosa but binds poorly to those of other bacteria. Cefsulodin has the ability to readily pass through the outer wall of P. aeruginosa and is poorly hydrolyzed by most chromosomal beta-lactamases. It is partially destroyed by the carbenicillinases of P. aeruginosa that are plasmid mediated. Cefsulodin inhibits 50% of P. aeruginosa isolates at concentrations of 2-4 micrograms/ml. Cefsulodin acts synergistically with all aminoglycosides against 20%-80% of P. aeruginosa isolates.

Aminoglycosides↗
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Treatment of lower respiratory tract infections due to Pseudomonas aeruginosa in patients with cystic fibrosis.

Twelve patients who underwent 26 episodes of lower respiratory tract infection due to Pseudomonas aeruginosa were treated with aztreonam. Infectious episodes were severe in 11 patients, moderate in 10 patients, and mild in five patients. In 85% of the episodes, significant clinical improvement occurred, but in four severe episodes, the clinical response was unsatisfactory. The mean interval between initiation of treatment and improvement was seven days. Aztreonam was as clinically effective in the treatment of infections due to organisms susceptible to penicillins active against Pseudomonas as it was in the treatment of infections due to organisms resistant to these agents. P. aeruginosa was not permanently eradicated from the sputum of any of the patients treated with aztreonam. It did not cause any major adverse effects, and the only laboratory abnormality found was an increase in alkaline phosphatase, which occurred during 12 (46%) courses of therapy. Levels of alkaline phosphatase returned to normal after conclusion of treatment. Aztreonam was shown to be clinically effective in the treatment of lower respiratory infections due to P. aeruginosa in patients with cystic fibrosis.

Adolescent↗
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Infections due to gram-negative bacteria: an overview.

Infections caused by gram-negative bacteria have continued to be a major problem for hospitalized patients. Malignant necrotizing otitis due to Pseudomonas aeruginosa has been encountered with increasing frequency as the number of older diabetic patients has increased. Nosocomial sinusitis and bacteremia due to Escherichia coli, Klebsiella pneumoniae, Enterobacter species, or P. aeruginosa develop in hospitalized patients. Bacteremia due to E. coli, K. pneumoniae, or P. aeruginosa often follows instrumentation of the urinary, respiratory, or gastrointestinal tracts in the hospitalized patient. Mortality still is excessively high. Infections of skin structure, particularly decubitus ulcers in debilitated, bedridden patients, are due to a mixed gram-negative and anaerobic flora; frequently, P. aeruginosa and Enterobacteriaceae resistant to many older agents are the major pathogens. Similarly, osteomyelitis in patients who have undergone previous surgical procedures is caused by various multiply resistant Enterobacteriaceae and P. aeruginosa. In all of these situations, therapy has usually included an aminoglycoside. The availability of drugs such as aztreonam, which has activity directed at aerobic gram-negative bacilli, provides an alternative approach that has proved successful and can be evaluated in more detail in the coming years.

Arthritis, Infectious↗
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beta-Lactam antibiotics: structural relationships affecting in vitro activity and pharmacologic properties.

The essential nucleus of beta-lactam antibiotics is the four-membered ring, which can exist fused to form bicyclic ring structures or with moieties alone affixed to the four atoms. Penicillins, penems, carbapenems, and clavams have asymmetric centers at C-5 and C-6; cephalosporins and oxacephems have asymmetric centers at C-6 and C-7. Penicillins, cephalosporins, and monobactams require a beta-acylamino group for antimicrobial activity. Cephalosporins can undergo modification at C-3 and C-7 in both the alpha and beta position. Sulfur can be replaced with oxygen to achieve a more reactive nucleus. The most useful 7-beta-acylamino groups have been a 2-aminothiazolyl and an iminomethoxy or carboxypropyl group. Substitutions on the 7-alpha position increase beta-lactamase stability but decrease activity against staphylococci and Streptococcus pneumoniae. C-3 substitutions, particularly pyridinium groups, increase activity against Pseudomonas aeruginosa and Staphylococcus aureus. Carbapenems possess 6-alkyl substitutions in a trans configuration and inhibit aerobic, anaerobic gram-positive, and gram-negative bacteria. Monobactams are activated by sulfonic, phosphoric, or carboxyl groups, and their properties are related to the C-3-acyl side chain and their beta-lactamase stability to the C-4 grouping. beta-Lactamase inhibitors acylated by beta-lactamases can be penicillanic acid derivatives or clavulanates.

Anti-Bacterial Agents↗
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Achromobacter xylosoxidans bacteremia.

Achromobacter xylosoxidans is a rare cause of bacteremia. A case of community-acquired pneumonia and bacteremia due to Achromobacter in a patient with concomitant pulmonary tuberculosis is reported herein. The majority of patients who have developed achromobacter bacteremia have had a predisposition to infection (although the predisposing conditions have been diverse). Immunosuppression has been reported in only one of the seven patients with achromobacter bacteremia for whom detailed information is available. Achromobacter is usually resistant to ampicillin, cephalosporins, and aminoglycosides. Antipseudomonal penicillins and trimethoprim-sulfamethoxazole inhibit most isolates. Multiple-drug resistance is common, and optimal therapy is not known.

Alcaligenes↗
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Clinical pharmacology of the antimicrobial agents for infections in the ear, nose and throat.

Knowledge of which microorganisms cause infection in the ear, nose and throat must be coupled with an understanding of the susceptibility patterns of these bacteria as well as knowledge of the pharmacokinetic properties of antimicrobial agents. EVen though many of the bacteria which produce community-acquired infection are susceptible to the older agents, specific problems have developed with regard to species such as Hemophilus influenzae and to Staphylococcus aureus. Hospital-acquired infections due to Enterobacteriaceae may be resistant to the penicillin drugs and to some of the older cephalosporins and aminoglycosides. Use of the new agents often requires an understanding of how rapidly the compounds are cleared from the body or if they will accumulate to toxic levels in the elderly patient with decreased renal function. This article reviews the antimicrobial activity and clinical pharmacology of agents commonly used to treat infections of the ear, nose and throat.

Anti-Bacterial Agents↗