Ciprofloxacin: an overview and prospective appraisal.
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Administration, Oral↗
Biomedical subjects
H C Neu
Publications and source records attributed to H C Neu.
Post-antibiotic suppressive effect of ciprofloxacin against gram-positive and gram-negative bacteria.
The post-antibiotic suppressive effect (PAE) of different antibacterial agents against gram-positive bacteria has been known since the 1940s. Recently, it has been demonstrated that quinolone antimicrobial agents exert a PAE against gram-negative bacteria. In this study, the PAEs of ciprofloxacin against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Serratia marcescens, Staphylococcus aureus, and Streptococcus faecalis were determined. The differences in PAE determined by three different techniques--filtration, centrifugation, and dilution--were assessed for S. aureus and E. coli. Ciprofloxacin had a PAE by all three methods, and filtration was used in the majority of studies. A ciprofloxacin concentration of 3 micrograms/ml in Mueller-Hinton broth, pH 7.4, with two hours of exposure produced a PAE of three to four hours for gram-negative bacilli, and 1.9 hours for S. aureus, but had no effect on S. faecalis. Exposure of organisms in urine to 300 micrograms/ml of ciprofloxacin for two hours produced a two- to six-hour PAE for E. coli, S. marcescens, P. aeruginosa, and K. pneumoniae. Use of Mueller-Hinton broth with a magnesium concentration of 8 mM, pH 5.5, yielded similar results. Using human serum, a four-hour PAE was found for P. aeruginosa. There was a progressive increase in the PAE as the duration of ciprofloxacin exposure was increased from 0.9 hours to three hours. Increasing the ciprofloxacin concentration from two to eight times the minimal bactericidal concentration (MBC) for P. aeruginosa or from four to 16 times the MBC for E. coli did not cause a significant difference in the PAE using a two-hour exposure. Overall, ciprofloxacin produced an excellent PAE for most gram-negative bacteria and for S. aureus, but not for S. faecalis. A PAE caused by ciprofloxacin can be demonstrated in broth supplemented with magnesium, in urine, in serum, and in broth with the pH adjusted to an acidic level and with the increased magnesium concentration found in urine. These results support less frequent dosing programs for ciprofloxacin in the treatment of tissue and urinary infections.
Ciprofloxacin↗
In vitro activity of LY146032 (daptomycin), a new peptolide.
The in vitro activity of LY146032, a new peptolide antibiotic, was compared with those of vancomycin, teicoplanin, imipenem, amoxicillin and erythromycin. LY146032 inhibited 90% of Staphylococcus aureus and Staphylococcus epidermidis, including methicillin-resistant isolates at less than or equal to 1 microgram/ml. Its activity was comparable to those of vancomycin and teicoplanin. MIC90s for the beta-hemolytic streptococci varied from 0.25 microgram/ml for group B streptococci to 4 micrograms/ml for some group C and F streptococci. MICs for Streptococcus faecalis were in the range of 0.5 to 8 micrograms/ml, and the MIC90 4 micrograms/ml, compared to 4 micrograms/ml for vancomycin and 1 microgram/ml for teicoplanin. For some viridans streptococci the MICs were 4 micrograms/ml, whereas Streptococcus pneumoniae were inhibited by 0.5 microgram/ml. Corynebacterium JK species were inhibited by 0.5 microgram/ml, similar to vancomycin, and Listeria monocytogenes by 4 micrograms/ml. Neisseria species, Haemophilus species and enteric species were not inhibited. Most MBCs were within two-fold of the respective MICs. After 14 days passage in sub-inhibitory concentrations of LY146032, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus faecalis showed minimal increase in MICs. The activity of LY146032 was increased by adding Ca2+ and was reduced in an anaerobic environment. Overall, LY146032 is an extremely interesting new agent that inhibits gram-positive species.
Anti-Bacterial Agents↗
General concepts on the chemotherapy of infectious diseases.
Chemotherapy affects both the host and the microorganism. Antimicrobial agents have a profoundly adverse influence on the surrounding environment if they are improperly employed. In all chemotherapy, it is critical to know what the infecting organisms are, and if that information is not immediately available, to base chemotherapy on those organisms that characteristically produce the infection. It also is critical to have an understanding of the distribution of antibiotic-resistant microorganisms in one's community if the proper antimicrobial agent is to be selected. The host's status and site of the infection will impact upon the choice of drug. Infection in sites in which phagocytic function is poor, such as in heart valves or in the spinal fluid, or in individuals lacking complement, white blood cells, or immunoglobulins, must be treated with bactericidal agents. An understanding of the pathogenesis of infection caused by different microorganisms will provide insights into the type of therapy, duration, and amount of drug that must be used. Ultimately, the chemotherapy of infection should be based on integration of the activity of antimicrobial agents with their pharmacologic properties.
Anti-Bacterial Agents↗
Chloramphenicol and tetracyclines.
Tetracyclines have a broad range of clinical usefulness because of their broad antimicrobial spectrum of activity. For most routine gram positive and gram negative infections, alternative agents are available, but for Chlamydiae, Rickettsiae, Brucella, and Borrelia they still remain agents of choice. To some extent, gastrointestinal intolerance and inability to use these agents in patients with renal dysfunction have been overcome by the availability of doxycycline. Phototoxicity is a problem with this agent, however. Tetracycline is still useful as a sclerogenic agent for malignant effusions, and demeclocycline often is an agent of choice in therapy of inappropriate antidiuretic hormone secretion.
Bacterial Infections↗
New antibiotics: areas of appropriate use.
This has been an analysis of a number of agents whose clinical use has been approved in the past five years and of several agents that will undoubtedly be available within the next year. By the very nature of time alotted, the analysis had to be superficial. I believe that it is important to view all the agents because they cross each other in uses. I believe that areas of appropriate use exist for all of the compounds that I have discussed, and I also believe that cost and convenience will play increasingly important roles in the selection of what agent is most fitting, the definition of appropriate. In many infections it will not be possible to show a significant difference among drugs in a class, unless extremely large studies are undertaken. From my review of the literature in preparation for this meeting, I doubt these studies will be mounted. The infectious disease clinician must be familiar with all of the agents so that he or she can make judgments about which agent(s) make(s) the most sense for his/her hospital. I believe that it is fitting and proper for the infectious disease physician to appropriate the correct selection, methods of administration, and dose of antibiotic in many clinical situations, particularly ones in which parenteral agents are used. I hope the IDSA will have an impact on the proper use of the quinolones, monobactams, penems, and carbapenems. Our goal in the use of antimicrobial agents should be the selection of agents for prophylaxis, empiric therapy, and therapy for defined infections in a manner that results in cure, with reasonable cost and minimal damage to the microbial ecology.
Anti-Bacterial Agents↗
In-vitro activity of two new quinolone antimicrobial agents, S-25930 and S-25932 compared with that of other agents.
S-25930 and S-25932, two new 4-quinolones, were compared to ciprofloxacin, enoxacin, ofloxacin, norfloxacin, cefotaxime, gentamicin, trimethoprim, and ampicillin. S-25930 and S-25932 inhibited 90% of Enterobacteriaceae at less than or equal to 1 mg/l, usually differing only two-fold. The MIC90 for Pseudomonas aeruginosa was 8 mg/l for S-25930 and 16 mg/l for S-25932, compared to MICs of 1 to 8 for the other four quinolones. Both drugs inhibited Enterobacter cloacae, Serratia marcescens and Citrobacter freundii resistant to cefotaxime and Klebsiella species resistant to gentamicin and trimethoprim. The MICs90 were 0.125 and 0.25 mg/l against staphylococci, including methicillin-resistant Staphylococcus aureus and were superior to the MICs of other quinolones; activity against haemolytic streptococci at 1-2 mg/l was also superior. S-25930 and S-25932 showed rapid bactericidal activity at the MBC concentration and both agents showed post-antibiotic suppression of growth of bacteria. The agents were active in acid medium, but activity was reduced by magnesium at 9 mM. A stepwise increase in resistance was produced by serial passage in increasing concentrations of drug.
Anti-Bacterial Agents↗
In vitro activity of a new broad spectrum, beta-lactamase-stable oral cephalosporin, cefixime.
Cefixime is a new orally absorbed iminomethoxy, aminothiazolyl cephalosporin. It inhibits the majority, 90%, of Streptococcus pneumoniae, Streptococcus pyogenes, Branhamella catarrhalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Neisseria gonorrhoeae at concentrations less than or equal to 0.25 micrograms/ml. It inhibits 90% of the other members of the Enterobacteriaceae at concentrations less than 1 microgram/ml, with the exception of some strains of Enterobacter spp., Citrobacter freundii and Morganella morganii, Cefixime does not inhibit enterococci, Listeria, Pseudomonas aeruginosa, Acinetobacter, Bacteroides spp. or staphylococci. In general, cefixime has in vitro activity superior to cephalexin, cephradine, cefadroxil and cefaclor against all bacteria with the exception of staphylococci. Cefixime is not destroyed by most of the common plasmid and chromosomal beta-lactamases and its activity is not reduced by serum, blood or urine. Cefixime overall has excellent in vitro activity against the commonly encountered respiratory and urinary tract pathogens.
Bacteria↗
[Clinical study on development of resistance of respiratory bacterial pathogens to ofloxacin and ciprofloxacin].
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Adult↗
Activity of A-56268 compared with that of erythromycin and other oral agents against aerobic and anaerobic bacteria.
A-56268 was compared with erythromycin, roxithromycin (RU 28965), and perorally administered antimicrobial agents. Its in vitro activity was similar to that of erythromycin and slightly greater than that of roxithromycin, with beta-hemolytic streptococci and Streptococcus pneumoniae inhibited by less than 2 micrograms of A-56268 per ml (50% inhibited by 0.06 microgram/ml). Streptococcus pyogenes, S. agalactiae, S. Pneumoniae, and S. faecalis resistant to erythromycin were resistant to A-56268, and 4 micrograms/ml inhibited 90% of Haemophilus influenzae isolates.
Anti-Bacterial Agents↗
Comparative antibacterial activity of a new oral cephalosporin, BMY-28100.
BMY-28100 is a new oral cephalosporin which had in vitro activity superior to that of cephalexin and cefaclor against staphylococci, beta-hemolytic streptococcal species, and Streptococcus pneumoniae. It inhibited beta-lactamase-producing Haemophilus influenzae, Neisseria gonorrhoeae, 50% of Streptococcus faecalis isolates, Listeria monocytogenes, and 50 to 75% of Escherichia coli and Klebsiella species at less than or equal to 8 micrograms/ml, but high producers of beta-lactamase were resistant. Enterobacter, Citrobacter, Morganella, Providencia, and Pseudomonas species and Bacteroides fragilis were resistant. BMY-28100 was more stable than cefaclor against hydrolysis by beta-lactamases.
Bacteria↗
In vitro activity and beta-lactamase stability of a new monobactam, B0-1165.
B0-1165 is a 1-carboxy-1-cyclopropoxyamino,4-fluoromethyl monobactam. It inhibited the majority of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter diversus, Aeromonas hydrophila, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Yersinia enterocolitica, Haemophilus influenzae, Neisseria gonorrhoeae, and Salmonella and Shigella species at less than or equal to 0.125 microgram/ml. Overall, its in vitro activity was similar to that of aztreonam, cefotaxime, and ceftazidime, with minor differences in the MICs for individual isolates. Enterobacter species and Citrobacter freundii which were derepressed for beta-lactamase production and had higher MICs of aztreonam and ceftazidime had MICs that ranged from 4 to 32 micrograms/ml. B0-1165 had activity against Pseudomonas aeruginosa similar to that of aztreonam but lower than that of ceftazidime and carumonam. Pseudomonas maltophilia and other Pseudomonas species were resistant or had MICs of 32 micrograms/ml, as did Acinetobacter species. B0-1165 did not inhibit streptococcal, staphylococcal, or anaerobic species, such as Clostridium and Bacteroides species. B0-1165 was not hydrolyzed to any appreciable extent by common plasmid- and chromosomally Richmond-Sykes type 1a-, 1c-, and 1d-mediated beta-lactamases. It inhibited the Enterobacter cloacae P99 and inducible Pseudomonas aeruginosa beta-lactamases. B0-1165 was a poor inducer of beta-lactamase, but exposing E. cloacae and C. freundii to B0-1165 selected for resistant isolates. Overall, B0-1165 had in vitro properties similar to those of other monobactams currently available or under investigation.
Aztreonam↗
In vitro activity and beta-lactamase stability of a new penem, CGP 31608.
The in vitro activity of CGP 31608, a new penem, against aerobic and anaerobic organisms was evaluated and compared with those of other beta-lactams. CGP 31608 inhibited Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Proteus mirabilis, Citrobacter diversus, and Salmonella, Shigella, Aeromonas, and Yersinia spp. with MICs for 50% of the strains (MIC50s) of 2 to 4 micrograms/ml and MIC90s of 4 micrograms/ml, compared with cefotaxime, ceftazidime, aztreonam, and imipenem MICs of less than 0.25 microgram/ml. MIC90s were 8 micrograms/ml for Enterobacter species and C. freundii, for which other agents had MICs of 32 micrograms/ml, except imipenem, which had equal activity. The MIC90 for Proteus vulgaris, Morganella morganii, Providencia stuartii, and Providencia rettgeri was 8 micrograms/ml, compared with less than 2 micrograms/ml shown by the other agents. Acinetobacter species resistant to other agents except imipenem were inhibited by 4 micrograms/ml, as were Pseudomonas aeruginosa, including piperacillin-, ceftazidime-, and gentamicin-resistant isolates. The MIC for P. cepacia, P. fluorescens, and P. acidovorans was less than or equal to 8 micrograms/ml, but that for P. maltophilia was greater than or equal to 128 micrograms/ml. Hemolytic streptococci A, B, C, G, and F were inhibited by less than 1 micrograms/ml, but the MIC for Streptococcus faecalis was greater than or equal to 32 micrograms/ml. MICs for Staphylococcus aureus methicillin-susceptible and -resistant strains were less than or equal to 1 microgram/ml, as were those for methicillin-susceptible and -resistant S. epidermidis. Bacteroides fragilis and Clostridium species and Fusobacterium spp. were inhibited by less than or equal to 4 micrograms/ml. CGP 31608 was not hydrolyzed by plasmid beta-lactamases TEM-1, TEM-2, SHV-1, PSE-1, OXA-2, PSE-4, or by S. aureus. Chromosomal beta-lactamases of type Ia in Enterobacter cloacae P99 and Morganella morganii, Ic in P. vulgaris, K-1 in K. oxytoca, and Id in P. aeruginosa also did not hydrolyze CGP 31608. It inhibited TEM-1, but the 50% inhibitory concentration was 14.2 micrograms/ml compared with 0.15 micrograms/ml for the P99 enzyme. CGP 31608 induced beta-lactamases in P. aeruginosa, E. cloacae, C. freundii and Providencia rettgeri, but there was no increase in MICs for the isolates and it did not select strains derepressed for beta-lactamase production. Synergy of CGP 31608 and gentamicin was found against 90% P. aeruginosa, 60% Enterobacter cloacae, and 50% Serratia marcescens strains. No synergy was found with rifampin. A postantibiotic effect was found against E. coli.
Anti-Bacterial Agents↗
Epidemiologic factors affecting antimicrobial resistance of common bacterial isolates.
The pattern of antimicrobial resistance of common bacterial isolates obtained from various groups of patients at a large tertiary-care center was compared with the pattern of resistance seen at a primary-care community hospital. At the tertiary-care center, significant differences in susceptibility were seen between pediatric and adult groups. In the tertiary-care center, the inpatients were more likely than the outpatients to have resistant staphylococcal and enterobacterial strains. Comparison of the overall resistance at the tertiary-care center and the primary-care hospital showed that resistance to cephalosporins, piperacillin, and aminoglycosides was significantly higher at the tertiary-care hospital than at the community hospital. Striking differences were noted in the resistance of nosocomial Enterobacter and Citrobacter isolates. Hospitals should be cautious in extrapolating nationwide data to their particular institutions.
Adolescent↗
In vitro activity of two new aryl-fluoroquinolone antimicrobial agents, difloxacin (A-56619) and A-56620 compared to that of other antimicrobial agents.
The in vitro activity of difloxacin (A-56619) and A-56620, two new aryl-difluoroquinolones, was compared to that of other new quinolones and several parenteral and oral antimicrobial agents. A-56620 inhibited 90% of Enterobacteriaceae at less than or equal to 1 microgram/ml, Staphylococcus aureus 0.25 micrograms/ml, hemolytic streptococci 2 micrograms/ml, Pseudomonas aeruginosa 2 micrograms/ml, Bacteroides sp. and Clostridium at 8 micrograms/ml. A-56620 was equal or 2-fold more active than norfloxacin and ofloxacin, and 2-8-fold less active than ciprofloxacin. Difloxacin had similar in vitro activity with many isolates but usually was 2-8-fold less active than A-56620. Both agents inhibited beta-lactamase positive Haemophilus influenzae (MIC 0.015 micrograms/ml) and Neisseria gonorrhoeae (MK less than or equal to 0.008 micrograms/ml). Both agents were more active against streptococci and Streptococcus pneumoniae than norfloxacin, ofloxacin and enoxacin, but not more active than ciprofloxacin. They inhibited Enterobacter cloacae, Citrobacter freundii and Serratia marcescens resistant to cephalosporins and methicillin-resistant S. aureus and Staphylococcus epidermidis. Spontaneously resistant mutants were seen with Enterobacteriaceae, P. aeruginosa and S. aureus at a frequency similar to that found for other new quinolones. These agents show overall in vitro activity comparable to other quinolones in clinical trial or recently approved for clinical use.
Anti-Bacterial Agents↗
Synergy of imipenem--a novel carbapenem, and rifampin and ciprofloxacin against Pseudomonas aeruginosa, Serratia marcescens and Enterobacter species.
Although imipenem inhibits most bacteria at very low concentrations, some Pseudomonas aeruginosa, Serratia marcescens and Enterobacter species are resistant or become resistant after exposure. At concentrations of rifampin equivalent to those attainable in man after daily oral ingestion of 600 mg, synergy of imipenem and rifampin was found for 52% of 62 P. aeruginosa and an additive effect for 37%. Against 30 S. marcescens synergy of imipenem and rifampin was not found, but an additive effect was noted for 47% of the isolates. With 32 Enterobacter isolates 35% were synergically inhibited, and an additive effect was found against 38% of the strains. Imipenem and ciprofloxacin were synergistic for 8% of P. aeruginosa and 22% of Enterobacter. Eighty-seven percent of P. aeruginosa isolates with imipenem MIC greater than or equal to 4 micrograms/ml were synergistically inhibited by the combination of imipenem-rifampin. Imipenem MIC and MBC were lowered to 1-2 micrograms/ml and to 2-4 micrograms/ml for rifampin. MIC of imipenem and ciprofloxacin were 0.5-2 and 0.05-0.1 micrograms/ml, respectively. When a triple combination of imipenem-rifampin-ciprofloxacin was studied, 62% of P. aeruginosa, 32% of Enterobacter spp. and 47% of S. marcescens were synergistically inhibited.
Ciprofloxacin↗
Cephalosporins in the treatment of meningitis.
The synthesis of new cephalosporin antibiotics has provided agents which can effectively be used to treat most of the different forms of meningitis. None of the first generation cephalosporins can be considered acceptable as agents to treat meningitis. Cefuroxime can be used to treat meningitis due to Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis in children. Agents such as cefotaxime and ceftriaxone are appropriate for neonatal meningitis due to Escherichia coli and group B streptococci, but not Listeria monocytogenes. Cefotaxime, ceftriaxone, ceftizoxime and ceftazidime have all proved effective as therapy of meningitis in children and adults when the pathogens are pneumococci, H. influenzae or N. meningitidis, but they have not been shown to yield an improved mortality or lower morbidity in spite of much greater cerebrospinal fluid (CSF) bactericidal titres. Cefotaxime, ceftizoxime, ceftriaxone and ceftazidime have been effective as therapy of meningitis due to E. coli, K. pneumoniae and Proteus species, but failures have occurred with all of the cephalosporins when used to treat meningitis due to Enterobacter spp. and Serratia marcescens. Only ceftazidime yields adequate CSF concentrations to treat meningitis due to Pseudomonas aeruginosa. Overall, the cephalosporins can now be considered a major component of the therapy of acute bacterial meningitis irrespective of the age group to be treated.
Animals↗
Editors' roundtable: current formulas for P & T Committee success. (Part 2).
In the second and final part of their recent roundtable discussion, the editors of Hospital Formulary express their views on numerous issues, including monitoring the use of approved drugs for unapproved indications, achieving and sustaining alterations in prescribing practices, and the establishment of guidelines for therapeutic substitution. All four editors--Arthur G. Lipman, PharmD, Harold C. Neu, MD, Bramah N. Singh, MD, PhD, and Michael Weintraub, MD--share the sentiment that most P & T Committees function as vital, effective bodies with responsibility for decision-making that has a significant impact on the day-to-day care of patients.
Drug Utilization↗