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PubMed1987

Treatment of ciprofloxacin- and ceftizoxime-induced resistant gram-negative bacilli.

Gram-negative bacilli that had been selected for resistance to either ciprofloxacin or ceftizoxime as a result of previous exposure to these agents were inoculated into semipermeable subcutaneous chambers in rabbits, modeling a locally neutropenic closed-space infection. Five resistant organisms, one Serratia marcescens (157) and four Pseudomonas aeruginosa (864, 876, 913, and 915) strains, were selected by previous therapy with ciprofloxacin, and six Pseudomonas strains (833, 845, 864, 876, 913, and 915) were selected by previous therapy with ceftizoxime. Animals were treated with either single antibiotics or combinations of antibiotics for four days, and the response was determined by quantitative bacterial count measurements. The selected (induced) resistance was stable for at least four days, both in vivo and in vitro, but was limited to the antibiotic class of the agent used for induction. Four of five isolates for which resistance had been induced by ciprofloxacin returned to preinduction susceptibility by the eight day of subculture. Organisms that were selected for resistance to ciprofloxacin were successfully treated by a combination of azlocillin and amikacin, and were as sensitive to that regimen as were the parent, uninduced strains. Organisms selected for resistance by pretreatment with ceftizoxime were successfully treated by the combination of ciprofloxacin plus azlocillin, and this regimen was also equally active against the selected strains as it was against the parental isolates. Although selection or induction of resistance is a potential problem with all new potent antimicrobial agents, it appears that infections due to these isolates can still be treated successfully through the use of appropriate combination chemotherapy.

Amikacin↗
PubMed1986

[In vitro susceptibility of gram-negative bacteria isolated from urinary tract infections to acylureidopenicillins].

Ureidopenicillins exert antibacterial activity on many Gram negative bacteria and also some Gram positive bacteria Two acylureido penicillins called azlocillin and mezlocillin have been introduced recently into medical practice in many countries as broad spectrum antibiotics. In this communication we present the sensitivity of Gram negative bacteria isolated from urinary tract infection of pediatric age patients to azlocillin, mezlocillin, another semisynthetic penicillin called pipercillin and aminoglycoside antibiotic gentamicin by MIC and disk-diffusion methods. The results are discussed in the view of the use of new semisythetic penicillins in clinical practice.

Azlocillin↗
PubMed1985

Susceptibility of Pseudomonas aeruginosa to beta-lactam antibiotics.

Since the discovery of carbenicillin in 1970, several groups of beta-lactam agents with remarkable activity against P. aeruginosa are actually available among penicillins such as ticarcillin, azlocillin, piperacillin, apalcillin and among cephalosporins: cefoperazone, cefsulodin as well as new structures including monobactams (aztreonam) and carbapenems with imipenem. An attempt to establish hierarchy in terms of weight for weight activity, particularly against susceptible isolates is made. The most active antimicrobial agents are: imipenem, apalcillin, ceftazidime, cefsulodin, piperacillin and azlocillin. The bactericidal activity is reported for virtually all of them but more accurate techniques such as time-killing curves are needed to make comparisons, because some discrepancies were reported. Nevertheless, among several factors affecting their inhibitory and bactericidal activities, some of them appeared predominant: inoculum effect and beta-lactamases. The different behavior of beta-lactam antibiotics may be in relation with other mechanisms such as impermeability. A few surveys on the resistance mechanism indicated that impermeability can be prevalent, instead beta-lactamases. But in any case, the enzyme distribution showed carbenicillinases (PSE-1, PSE-4) and OXA were observed with a high prevalence among ticarcillin-resistant isolates and more recently cephalosporinases. These drugs acted synergistically with all of the aminoglycosides in vitro against P. aeruginosa isolates and also in animal models of infection. If the synergism appeared to play a major role in the therapy of P. aeruginosa infections, these new beta-lactam antibiotics offer the possibility of other approaches to combination therapy.

Ampicillin↗
PubMed1985

In vitro effects of ureidopenicillins on human polymorphonuclear leukocytes.

The in vitro effects of mezlocillin, azlocillin and piperacillin on chemotaxis and adhesivity of human leukocytes were comparatively studied. After incubation with all these antibiotics, chemotactic and adhesivity counts were similar to those of the antibiotic-free cells. Scanning electron microscope examination showed enlargement of surface and length measurements after incubation with azlocillin (P less than 0.005 and P less than 0.001) and mezlocillin (P greater than 0.05 and P less than 0.05), while piperacillin produced no alteration. These findings could provide additional information in the study of leukocyte/antibiotics interactions.

Azlocillin↗
PubMed1982

[Comparison of in vitro bacteriostatic effect of five betalactamins against Pseudomonas aeruginosa (author's transl)].

In vitro activity of two penicillins (ticarcillin and azlocillin) and three cephalosporins (cefoperazone, cefsulodin and ceftazidime) was compared against one hundred clinical isolates of Pseudomonas aeruginosa originated in two different Paris hospitals. Twenty strains were resistant to carbenicillin at a concentration of 128 mg/l. Minimal inhibitory concentrations (MICs) were determined by a twofold agar dilution method. The required ceftazidime concentration to inhibit 90 p. cent of the carbenicillin-susceptible isolates was 1,9 mg/l. To achieve the same inhibition, 3,9 mg of cefsulodin, 12 mg of cefoperazone, 14 mg of azlocillin or 38 mg of ticarcillin per liter were needed. Against the 209 carbenicillin-resistant isolates, ceftazidime remained active at concentrations lower than 2 mg/l in 90 p. cent of the cases. To obtain such an inhibition with the other antibiotics higher concentrations were needed.

Azlocillin↗
PubMed1994

In vitro evaluation of newer beta-lactam antibiotics against gram negative bacilli isolated from neutropenic patients.

The in-vitro susceptibility pattern to newer beta lactams namely Ticer/Clav, Azlocillin, Piperacillin and Imipenem was determined with 50 clinical strains isolated from neutropenic patients with strains isolated from neutropenic patients with sepsis, with an objective of evolving a strategy for empirical antibiotic therapy for febrile neutropenic patients. The MIC90 value for Imipenem for the Gram negative bacilli tested, other than Pseudomonas was < 0.25 mcg/ml therapy revealing a high degree of susceptibility, while for Ps. aeruginosa and related species MIC50 and MIV90 values were 2.0 and 64.0 micrograms/ml respectively. A comparatively lower degree of susceptibility was found among Gram negative bacilli included in the study to ticar/clavu, azlocillin and piperacillin indicating a moderate degree of resistance to these antibiotics. The data from this study suggests that (i) Ureidopenicillins with an aminoglycoside should be effective therapy for proven Pseudomonas and other Gram negative sepsis in febrile neutropenic patients. (ii) Imipenem would be the antibiotic of choice in Gram negative bacterial sepsis in febrile neutropenic patients where the organism is resistant to cephalosporins and ureidopenicillins.

Anti-Bacterial Agents↗
PubMed1996

[Enhancement of treatment efficacy in experimental plague by the sequential administration of antibiotics].

It was shown that the use of ampicillin, azlocillin or polymyxin 24 or 96 hours after the plague infection at the background of the every-day use of rifampicin in the doses protecting only 30 per cent of the animals from death provided 80-100-percent survival of the animals. With the every-day use of ampicillin, azlocillin or polymyxin in succession with rifampicin there was observed a 3-fold increases in the survival of the albino mice as compared to those exposed to an analogous dose of rifampicin alone. A decrease in the number of administrations of the above drugs and an increase in the intervals between the administration also resulted in a significant rise of the animal survival in comparison with that after the every-day use of a similar dose of rifampicin.

Ampicillin↗
PubMed1997

Pseudomonas aeruginosa infection in embryonated hen's eggs. An alternative in vivo model for the screening of antibacterial substances.

Embryonated hens' eggs can be reliably infected by Pseudomonas aeruginosa in laboratory experiments. Therapy tests with the antibiotics azlocillin (CAS 37091-66-0) and gentamicin (CAS 13291-74-2) on this type of infected hens' eggs demonstrate that this test system offers a realistic alternative to septic experiments with small laboratory rodents. Chick embryos survive a lethal Pseudomonas infection when azlocillin or gentamicin in a relevant therapeutic dose are administered immediately after the infective agent. The use of Pseudomonas infected chick embryos in the screening for new antiinfectives allows, therefore, a considerable reduction of the number of laboratory rodents required.

Animal Testing Alternatives↗
PubMed1982

Comparative activity of six beta-lactam antibiotics against strains of Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae.

The minimum inhibitory concentrations (MIC) of penicillin G, ampicillin, mezlocillin, azlocillin, cephalothin and cefoxitin were determined for 47 strains of Haemophilus influenzae, 68 strains of Neisseria meningitidis and 45 strains of Streptococcus pneumoniae. These strains were isolated during the past three years from patients with acute bacterial meningitis. Three strains of H. influenzae were ampicillin-resistant while no pneumococcus or meningococcus strain was penicillin-resistant. Mezlocillin was the most potent antibiotic against the Haemophilus and pneumococcus strains, followed closely by azlocillin. Mezlocillin inhibited 77.7% of the meningococci strains tested at a concentration of 0.03 mg/l. Penicillin G was the most effective of the drugs against these strains. It inhibited 100% at a concentration of 0.5 mg/l. The cephalosporins were the least active of the six beta-lactam antibiotics tested.

Anti-Bacterial Agents↗
PubMed1994

Changing causes of septicaemia in paediatric oncology patients: effect of imipenem use.

One hundred and fifty-four episodes of septicaemia occurred in 78 patients on a Paediatric Oncology Unit over 2 years. Septicaemias with Gram-positive bacteria were more common than with Gram-negative organisms, coagulase-negative staphylococci (CNS) being the commonest pathogens. The mortality rate in patients with septicaemia was 1.9%. Azlocillin and gentamicin comprised the first-line of empirical antibiotic therapy for suspected infection for the first 10 months of the study; imipenem with cilastatin, as monotherapy, was used subsequently. More isolates of enterococci, and fewer isolates of Enterobacter, were seen after the introduction of imipenem. The use of imipenem was associated with an increased frequency of resistance to flucloxacillin in CNS. Such strains have been shown to contain sub-populations of cells that are resistant to imipenem. A clinical response was achieved in 82.9% of septicaemic episodes treated with imipenem, compared with 62.7% for azlocillin and gentamicin. However, imipenem as monotherapy may not be appropriate in central venous catheter related infections, owing to the frequent occurrence of imipenem-resistant organisms, CNS and Pseudomonas spp., in this situation.

Bacteremia↗
PubMed1983

Susceptibility of gram-negative bacteria and Staphylococcus aureus to combinations of ticarcillin and clavulanic acid.

Four hundred and fifty-nine blood culture isolates were tested for susceptibility to ticarcillin alone and ticarcillin plus clavulanic acid, a potent beta-lactamase inhibitor. The susceptibilities of the Staphylococcus aureus strains to cloxacillin, methicillin, vancomycin, rifampicin, cefoperazone, ceftriaxone and moxalactam and of the gram-negative strains to Augmentin, azlocillin, mezlocillin, piperacillin, cefoperazone, ceftriaxone, cefotaxime, cefsulodin and tobramycin were also measured. Seventy-one percent of staphylococcal strains were beta-lactamase positive. In the presence of clavulanic acid the ticarcillin spectrum was extended to include beta-lactamase producing Staphylococcus aureus, Serratia marcescens and Klebsiella. All the ticarcillin-resistant Enterobacteriaceae were rendered ticarcillin-sensitive by clavulanic acid. The anti-Pseudomonas activity of ticarcillin plus clavulanic acid differed little from that of azlocillin and piperacillin and was comparable to that of the third generation cephalosporins. The combination of ticarcillin with clavulanic acid should be tested in the treatment of patients with infections caused by ticarcillin-sensitive and ticarcillin-resistant bacteria.

Clavulanic Acid↗
PubMed1984

Comparative study of the ability of four aminoglycoside assay techniques to detect the inactivation of aminoglycosides by beta-lactam antibiotics.

In vitro inactivation of aminoglycosides (tobramycin, gentamicin, and amikacin) by beta-lactams (cefazolin, cefotaxime, moxalactam, carbenicillin, piperacillin, mezlocillin, and azlocillin) was measured using the enzyme-mediated immunoassay (EMIT), fluorescence polarization immunoassay ( TDX ), radioimmunoassay (RIA), and bioassay. No significant inactivation of aminoglycosides was produced by high levels of the three cephalosporins as measured by EMIT, RIA, or bioassay. Inactivation of tobramycin and gentamicin by mezlocillin and azlocillin was comparable to that seen with piperacillin but less than that with carbenicillin. In general, the bioassay detected the greatest degree of aminoglycoside inactivation and the EMIT assay detected the least for all drug combinations. The TDX and RIA techniques were equivalent in their ability to detect aminoglycoside inactivation by beta-lactam antibiotics.

Aminoglycosides↗
PubMed1984

Unpredictable interactions between cefotetan and penicillins or aminoglycosides.

The bacteriostatic and bactericidal activity of gentamicin, amikacin, piperacillin, azlocillin, ampicillin, benzyl penicillin, and oxacillin against 85 selected isolates was measured alone and in the presence of subinhibitory concentrations of cefotetan. A potential for antagonistic interactions between cefotetan and acylamino penicillins (piperacillin greater than azlocillin greater than ampicillin) were observed with some strains; synergy was suggested with other isolates, however, Bacteriostatic and bactericidal activity of the two aminoglycosides was enhanced by cefotetan with most gram-negative bacilli, but bactericidal activity was significantly diminished with 4 of 65 strains. Piperacillin and cefotetan were clearly antagonistic with 11 of 44 strains and synergistic with 4 of 44 strains of gram-negative bacilli: the remaining 21 strains gave off scale end points and could not be analyzed in that way.

Aminoglycosides↗
PubMed1984

National survey of antibiotic resistance in Pseudomonas aeruginosa.

The antibiotic susceptibility of 1866 consecutive non-replicate clinical isolates of Pseudomonas aeruginosa from 24 British hospitals was examined. Antibiotics tested and resistance breakpoints selected were: carbenicillin (MIC greater than 128 mg/l), azlocillin (greater than 32 mg/l), cefotaxime (greater than 16 mg/l), cefoperazone (greater than 16 mg/l), ceftazidime (greater than 16 mg/l), amikacin (greater than 4 mg/l) and gentamicin (greater than 2 mg/l). Resistance frequencies detected were: carbenicillin 9.6%, azlocillin 3.9%, cefotaxime 19.0%, cefoperazone 4.3%, ceftazidime 0.3%, amikacin 3.8%, and gentamicin 5.5%.

Anti-Bacterial Agents↗
PubMed1985

Comparative in-vitro activity of ciprofloxacin against non-fermenters.

The in-vitro activity of ciprofloxacin, a quinolone-carboxylic acid derivative, was compared with those of carbenicillin, azlocillin, cefsulodin, ceftazidime, tobramycin and amikacin against 187 non-fermenters. Only one of the 131 strains of Pseudomonas spp. was not inhibited by 1 mg/l of ciprofloxacin, while these isolates appeared highly resistant to carbenicillin, azlocillin and cefsulodin. Ciprofloxacin was also the best agent against Flavobacterium, Alcaligenes faecalis and Acinetobacter calcoaceticus with MIC90's respectively of 0.5, 4 and 8 mg/l. This new compound appeared bactericidal, and we found a small or no inoculum effect with ciprofloxacin.

Anti-Bacterial Agents↗
PubMed1985

Use of an in-vitro kinetic model to study antibiotic combinations.

A two compartment pharmacokinetic model was used to study combinations of piperacillin with N-formimidoyl thienamycin or amikacin, and azlocillin with netilmicin against strains of Pseudomonas aeruginosa. Antibiotic antagonism seen with in-vitro static tests of piperacillin and thienamycin did not occur with the kinetic model. Piperacillin plus amikacin showed enhanced activity, and azlocillin prevented bacterial regrowth seen with netilmicin alone during multiple dosing experiments at high bacterial inocula. This model is useful in the study of antibiotic combinations.

Anti-Bacterial Agents↗
PubMed1981

Susceptibility of pneumococci to 14 beta-lactam agents: comparison of strains resistant, intermediate-resistant, and susceptible to penicillin.

To measure the susceptibility of penicillin-resistant pneumococci to newer beta-lactam agents, we evaluated 54 selected strains recovered from patients with bacteremia or meningitis. Three groups of pneumococci were tested: penicillin-susceptible strains, strains with intermediate penicillin resistance, and penicillin-resistant strains. Minimal inhibitory concentrations of benzyl penicillin, oxacillin, cephalothin, cefamandole, cefoxitin, moxalactam (LY127935), cefotaxime (HR756), piperacillin, pirbenicillin, N-formimidoyl thienamycin (MK0787), cefoperazone (T1551), mezlocillin, azlocillin, and mecillinam were determined. For all groups of pneumococci tested, cefotaxime, and particularly thienamycin, had the greatest activity. Piperacillin, mezlocillin, and azlocillin had activity similar to that of benzyl penicillin. Cefoperazone had less activity than penicillin against strains with penicillin minimal inhibitory concentrations of less than 1 microgram/ml but greater activity than penicillin against strains with greater resistance. Oxacillin, cephalothin, cefamandole, and pirbenicillin all had less activity for each group of pneumococci tested; moxalactam, cefoxitin, and mecillinam had the least activity. The relative differences in susceptibility to penicillin of each group of pneumococci tested were similar for each of the beta-lactam agents tested. The clinical effectiveness of cefotaxime and thienamycin for therapy of disease due to penicillin-resistant pneumococci needs further evaluation, and of particular interest will be the levels of these drugs which can be achieved in cerebrospinal fluid.

Cephalosporins↗
PubMed1983

Binding of monobactams to penicillin-binding proteins of Escherichia coli and Staphylococcus aureus: relation to antibacterial activity.

A series of novel monocyclic beta-lactam antibiotics having side chains related to penicillin, piperacillin, azlocillin, and cefotaxime were examined with respect to binding to essential penicillin-binding proteins (PBPs) in Escherichia coli and Staphylococcus aureus. In the penicillin series, there was poor binding to all essential PBPs of E. coli (greater than 100 micrograms/ml) but good binding to PBPs 1, 2, and 3 of S. aureus (approximately 1 microgram/ml). In the piperacillin and azlocillin series, there was good binding to PBP 3 of E. coli (0.1 microgram/ml) and PBPs 1, 2, and 3 of S. aureus (approximately 1 microgram/ml). In the cefotaxime series, there was generally good binding to PBP 3 of E. coli (0.1 micrograms/ml) but poor binding to PBPs 1, 2, and 3 of S. aureus (greater than or equal to 100 micrograms/ml). With a few exceptions in the cefotaxime series, antibacterial activity paralleled essential PBP binding. Binding studies with radioactively labeled compounds revealed no additional essential monobactam-binding proteins in the two organisms. The studies suggest that monobactams are intrinsically active against both gram-positive and gram-negative bacteria; the activity spectrum of a given monobactam is determined by the binding to essential PBPs, which in turn is determined by the nature of the substituents on the beta-lactam nucleus.

Aminoacyltransferases↗