ABSTRACT
Lyme disease is one of most common vector-borne diseases, reporting more than 300,000 cases annually in the United States. Treating Lyme disease during its initial stages with traditional tetracycline antibiotics is effective. However, 10-20% of patients treated with antibiotic therapy still shows prolonged symptoms of fatigue, musculoskeletal pain, and perceived cognitive impairment. When these symptoms persists for more than 6 months to years after completing conventional antibiotics treatment are called post-treatment Lyme disease syndrome (PTLDS). Though the exact reason for the prolongation of post treatment symptoms are not known, the growing evidence from recent studies suggests it might be due to the existence of drug-tolerant persisters. In order to identify effective drug molecules that kill drug-tolerant borrelia we have tested two antibiotics, azlocillin and cefotaxime that were identified by us earlier. The in vitro efficacy studies of azlocillin and cefotaxime on drug-tolerant persisters were done by semisolid plating method. The results obtained were compared with one of the currently prescribed antibiotic doxycycline. We found that azlocillin completely kills late log phase and 7-10 days old stationary phase B. burgdorferi. Our results also demonstrate that azlocillin and cefotaxime can effectively kill in vitro doxycycline-tolerant B. burgdorferi. Moreover, the combination drug treatment of azlocillin and cefotaxime effectively killed doxycycline-tolerant B. burgdorferi. Furthermore, when tested in vivo, azlocillin has shown good efficacy against B. burgdorferi in mice model. These seminal findings strongly suggests that azlocillin can be effective in treating B. burgdorferi sensu stricto JLB31 infection and furthermore in depth research is necessary to evaluate its potential use for Lyme disease therapy.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Azlocillin/administration & dosage , Borrelia burgdorferi/drug effects , Lyme Disease/drug therapy , Animals , Borrelia burgdorferi/physiology , Disease Models, Animal , Drug Evaluation, Preclinical , Drug Resistance, Bacterial , Female , Humans , Lyme Disease/microbiology , Mice, Inbred C3HABSTRACT
This work proposes a new method for the in vitro evaluation of the effect of UV irradiation on the production of free radicals and other reactive species during the photodecomposition of drugs. The method was based on the UV irradiation of antibiotics molecules to generate excited states that undergo to homolytic bond cleavages. These reactive species can be detected by their ability to oxidize the luminol, producing the electronically excited aminophtalate, which decays to the ground state releasing electromagnetic radiation in the visible zone of the spectrum. This method was applied to penicillin G, nafcillin, azlocillin and neomycin dissolved in water. It was found that the intensity of the luminol chemiluminescence emission (CL) was proportional to the concentration and dependent on the molecular structure of these drugs. Under the optimized conditions, it was found that penicillin and azlocillin were the most susceptible to photodegradation, while neomycin sulfate was the less affected by the UV light. It was observed that the addition to the antibiotics dissolutions of a hydro-alcoholic extract of petals of calyxes of Roselle reduced the CL intensity, indicating that the extract was able to scavenge the free radicals in the irradiated drugs. This result suggest that its addition to the antibiotics can help in the protection against the radicals formed during the exposition to solar light of patients treated with topic similar antibiotics.
Subject(s)
Anti-Bacterial Agents/radiation effects , Free Radical Scavengers/pharmacology , Free Radicals/antagonists & inhibitors , Hibiscus/chemistry , Luminescent Measurements/methods , Plant Extracts/pharmacology , Administration, Topical , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Azlocillin/administration & dosage , Azlocillin/chemistry , Azlocillin/radiation effects , Dermatitis, Phototoxic/etiology , Dermatitis, Phototoxic/prevention & control , Flowers/chemistry , Free Radicals/chemistry , Free Radicals/toxicity , Luminescent Agents/chemistry , Luminol/chemistry , Neomycin/administration & dosage , Neomycin/chemistry , Neomycin/radiation effects , Oxidation-Reduction , Penicillins/administration & dosage , Penicillins/chemistry , Penicillins/radiation effects , Sunlight/adverse effects , Ultraviolet Rays/adverse effectsABSTRACT
Brush border membrane vesicles (BBMV) were prepared from the rabbit small intestine for testing drug absorption potency through the enterocyte's apical membrane, which is an important compartment for drug oral absorption. Some modifications have been made to the traditional vesicle assay for adapting it to the 96-well plate format. The accumulation of 23 reference drugs was measured, and the data showed a good correlation with human oral absorption with a correlation coefficient R=0.853 (P<0.001), with the exception of a few false positive results. As the measured drug absorption may contain a membrane/protein binding component as well as drug uptake into vesicles, these two fractions can be discriminated by changing extravesicular osmolarity using different mannitol concentrations. This model can be applied for evaluating drug absorption rate/mechanisms, and helping drug selection in early drug research and development.
Subject(s)
Intestinal Absorption , Intestinal Mucosa/metabolism , Pharmaceutical Preparations/metabolism , Acetaminophen/administration & dosage , Acetaminophen/pharmacokinetics , Administration, Oral , Animals , Azlocillin/administration & dosage , Azlocillin/pharmacokinetics , Biological Transport, Active , Cefadroxil/administration & dosage , Cefadroxil/pharmacokinetics , Doxorubicin/administration & dosage , Doxorubicin/pharmacokinetics , Humans , Hydrogen-Ion Concentration , In Vitro Techniques , Intestine, Small/metabolism , Lamivudine/administration & dosage , Lamivudine/pharmacokinetics , Mannitol/chemistry , Osmolar Concentration , Ouabain/administration & dosage , Ouabain/pharmacokinetics , Pharmaceutical Preparations/administration & dosage , Pharmacokinetics , Phenolsulfonphthalein/administration & dosage , Phenolsulfonphthalein/pharmacokinetics , Rabbits , Zidovudine/administration & dosage , Zidovudine/pharmacokineticsABSTRACT
OBJECTIVE: To assess the effectiveness of combined therapy with azlocillin and amikacin in a group of neonates with sepsis caused by multiresistant staphylococci who were hospitalized in the neonatal intensive care unit of Hospital Ginecobstétrico "America Arias" in Havana, Cuba, from 1998 to 2000. METHODS: A retrospective study was carried out of the clinical and laboratory results obtained in 15 patients with sepsis caused by multiresistant staphylococci who received combined therapy with azlocillin and amikacin, according to hospital guidelines on the use of antibiotics. We used a broth microdilution method to study the patterns of resistance shown by isolated strains to 10 of the antibiotics in use. In vitro synergy tests, specifically the checkerboard technique with microtitration plates, were used to observe the effects of treatment in 8 patients. RESULTS: Twelve coagulase-negative staphylococci and three Staphylococcus aureus isolates showed five different patterns of resistance on the basis of their sensitivity to oxacillin, three aminoglycosides, and vancomycin. Six of the synergy tests showed a considerable synergistic effect, with an average three-fold reduction in the minimum inhibitory concentrations (MIC) of the two antibiotics used to treat the patients. No antagonistic effects were noted, and the combined antibiotics showed an overall clinical effectiveness of 91.7%. CONCLUSIONS: The test showed that the therapeutic combination used was effective, but further studies are needed before conclusive results are obtained.
Subject(s)
Amikacin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Azlocillin/therapeutic use , Sepsis/drug therapy , Staphylococcal Infections/drug therapy , Staphylococcus/drug effects , Amikacin/administration & dosage , Amikacin/pharmacology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Azlocillin/administration & dosage , Azlocillin/pharmacology , Drug Resistance, Multiple, Bacterial , Drug Synergism , Drug Therapy, Combination/therapeutic use , Humans , Infant, Newborn , Intensive Care Units, Neonatal , Microbial Sensitivity Tests , Models, Theoretical , Retrospective Studies , Staphylococcus aureus/drug effectsABSTRACT
BACKGROUND: Mobilising the stapes via the removal of the tympanosclerotic plaques from the oval window niche (effodation) and stapedectomy or malleovestibulopexy are the different procedures generally available for the surgical therapy of stapes fixation due to tympanosclerosis. These techniques bear a significant risk of sensory hearing loss. Here we analyse our results using the mobilisation technique together with locally applied antibiotics. PATIENTS: Nineteen ears in seventeen patients with tympanosclerosis involving the stapes and its footplate which underwent stapes mobilisation between 1991 and 1999 have been investigated retrospectively. According to the literature this operation has a high risk of cochlear hearing loss. To reduce this risk, azlocillin was instilled locally during removal of tympanosclerotic plaques. RESULTS: Different operation techniques have been used: classic type III with placement of a cartilage disc on the head of the stapes (4), interposition of the incus (3), interposition of the head of malleus (1), interposition of a ceramic-PORP (6) and cartilage columella in cases of significant stapes footplate erosion (3). In two operations the chain was intact and no reconstruction was necessary. Pure-tone-audiometry showed no significant decrease of bone-conduction thresholds. Preoperatively 4 (21.1%) ears had an average air-bone-gap < or = 30 dB, while postoperatively 15 (78.9%) ears had this level of hearing. CONCLUSIONS: Until the exact causes of the loss of hearing after mobilisation or stapedectomy in cases of tympanosclerosis are known, the local administration of antibiotics is certainly recommended, bearing in mind the initial hypothesis that infection may be jointly responsible for cochlear hearing loss on mobilisation or stapedectomy in cases of tympanosclerosis.
Subject(s)
Antibiotic Prophylaxis , Azlocillin/administration & dosage , Hearing Loss, Sensorineural/prevention & control , Otosclerosis/surgery , Postoperative Complications/prevention & control , Stapes Mobilization , Adult , Aged , Aged, 80 and over , Audiometry, Pure-Tone , Auditory Threshold/drug effects , Bone Conduction/drug effects , Female , Humans , Male , Middle Aged , Ossicular Prosthesis , Retrospective Studies , Treatment OutcomeABSTRACT
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.
Subject(s)
Ampicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Azlocillin/administration & dosage , Drug Therapy, Combination/administration & dosage , Penicillins/administration & dosage , Plague/drug therapy , Polymyxin B/administration & dosage , Animals , Drug Evaluation, Preclinical , Mice , Plague/mortality , Time FactorsABSTRACT
A young woman with acute upper extremity edema and ischemia after intraarterial drug injection is presented. Unsatisfactory results from standard treatment were the reason for changing the therapy to temporary thrombolysis, which led to significant improvement. Some days later severe impairment forced another attempt at applying standard therapy, again unsuccessful. Only after continuous intraarterial infusion of Iloprost, a new improvement occurred and saving of the hand was possible. It became obvious that more effective therapeutic measures ought to be applied when severe hand ischemia following intraarterial drug injection is present.
Subject(s)
Azlocillin/adverse effects , Hand/blood supply , Ischemia/chemically induced , Ischemia/drug therapy , Acute Disease , Adult , Azlocillin/administration & dosage , Diabetes Mellitus/drug therapy , Female , Humans , Iloprost/therapeutic use , Injections, Intra-Arterial , Ischemia/diagnostic imaging , Radiography , Thrombolytic TherapyABSTRACT
The kinetics of degradation of azlocillin sodium in four intravenous admixtures was investigated at different temperatures. The effect of temperature has been determined and from this data, by applying of Arrhenius-law, the stability of azlocillin sodium at 25 degrees C has been predicted and the t90 was determined. Admixtures containing azlocillin sodium (0.01 g ml-1) were prepared in 0.9% sodium chloride injection, in 5% dextrose solution, in 5% levulose solution and in Ringer's lactate solution. The admixtures were stored at 30 degrees, 40 degrees and 50 degrees C in either polyvinyl chloride bags and glass bottles. The change in the initial azlocillin sodium concentration was related to the type of intravenous solution. No dependence with material of container was found. After 24 hours, the change in the initial concentration of penicillin was less than 10% of the initial concentration in 0.9% sodium chloride and 5% levulose solution. However in Ringer's lactate and 5% glucose solution the t90 was lower. These results were found in agreement with experimental ones obtained at room temperature.
Subject(s)
Azlocillin/analysis , Azlocillin/administration & dosage , Drug Packaging , Drug Stability , Glass , Infusions, Intravenous , Polyvinyl Chloride , Solutions , Spectrophotometry, UltravioletABSTRACT
Seven febrile neutropenic adults with normal renal function were treated with intravenous gentamicin 4.5 mg/kg once a day in combination with azlocillin. Gentamicin serum concentrations 1, 2, 4, 8, and 24 h after a 30 min infusion were 10.9 +/- 0.6, 7.1 +/- 0.4, 4.2 +/- 0.2, 1.8 +/- 0.1 and 0.16 +/- 0.003 mg/L respectively. The pharmacokinetics were best described by a triphasic plot including a distribution phase (about 1/2 h) and two elimination phases, an early and late.
Subject(s)
Gentamicins/pharmacokinetics , Neutropenia/drug therapy , Adolescent , Adult , Aged , Azlocillin/administration & dosage , Female , Gentamicins/administration & dosage , Humans , Leukemia/drug therapy , Lymphoma/drug therapy , Male , Middle Aged , Neutropenia/metabolismABSTRACT
We report a case of endocarditis caused by a ciprofloxacin-resistant strain of Serratia marcescens in a 50-year-old female neutropenic patient with non-Hodgkin's lymphoma which occurred while receiving ciprofloxacin prophylaxis. She made poor progress on first line therapy with azlocillin and gentamicin by bolus injection t.d.s. The infection was finally eliminated by a regimen of continuous infusion of azlocillin and once daily gentamicin.
Subject(s)
Ciprofloxacin/pharmacology , Endocarditis, Bacterial/etiology , Lymphoma, Non-Hodgkin/complications , Serratia Infections/etiology , Serratia marcescens/drug effects , Azlocillin/administration & dosage , Azlocillin/therapeutic use , Ciprofloxacin/administration & dosage , Drug Resistance, Microbial , Female , Gentamicins/administration & dosage , Gentamicins/therapeutic use , Humans , Infusions, Intravenous , Middle AgedABSTRACT
Combination of a betalactam antibiotic (ampicillin or azlocillin) or polymyxin B with rifampicin were studied with their administration in succession at various intervals in an experimental model of plague infection of albino mice. It was shown that when the administration of the betalactams or polymyxin B preceded the administration of rifampicin, the efficacy of the preventive therapy considerably increased. The time of the intervals was noted to be of importance and should be predetermined for every subsequent administration.
Subject(s)
Drug Therapy, Combination/administration & dosage , Plague/prevention & control , Ampicillin/administration & dosage , Animals , Azlocillin/administration & dosage , Drug Administration Schedule , Mice , Plague/microbiology , Polymyxin B/administration & dosage , Rifampin/administration & dosageABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Gram-Negative Bacteria/drug effects , Neutropenia/microbiology , Azlocillin/administration & dosage , Azlocillin/therapeutic use , Clavulanic Acid , Clavulanic Acids/administration & dosage , Clavulanic Acids/therapeutic use , Drug Evaluation , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/drug therapy , Humans , Imipenem/administration & dosage , Imipenem/therapeutic use , Piperacillin/administration & dosage , Piperacillin/therapeutic use , Pseudomonas aeruginosa/drug effects , Sepsis/drug therapy , Sepsis/microbiology , Ticarcillin/administration & dosage , Ticarcillin/therapeutic useABSTRACT
Homograft heart valves are usually sterilized by exposure to multiple-antibiotic solutions at 4 degrees C for 24 hours. Several combinations of antibiotics have been proposed and discussed in the literature, but their toxicity to cusp endothelium has not been investigated yet. We studied the endothelial cell viability of porcine aortic valves by measuring their in vitro prostacyclin (PGI2) production after being exposed to different antibiotics solutions. Porcine aortic valves were immersed for 24 hours at 4 degrees C in RPMI medium to which antibiotics (Gentamycin 80 micrograms/ml, Azlocillin 500 micrograms/ml, Cloxacillin 25 micrograms/ml, Metronidazole 100 micrograms/ml, Amphotericin B 50 micrograms/ml, GACMA) were added separately or in combination. The basal and bradykinin (10 microM) stimulated PGI2 release of these valves in the medium were measured during consecutive incubation lasting 15 minutes at 37 degrees C, using a radioimmunoassay for 6-oxo-PGF1 alpha. Valves treated with the combination of all five antibiotics produced significantly less PGI2 in basal and stimulated conditions (1.64 +/- 0.63--7.25 +/- 1.73 ng/ml x cm2, p < 0.05) than the controls (4.66 +/- 0.66--30.55 +/- 3.84 ng/ml x cm2, p < 0.001). Although all antibiotics, when studied separately at the above mentioned concentrations, tended to reduce the biosynthesis of PGI2, amphotericin B was responsible for the most pronounced decrease in its production. The toxic effect of amphotericin B was dose dependent; at a low concentration (5 micrograms/ml), which is usually enough for antifungal action, toxicity was undetectable. At 50 micrograms/ml PGI2 production was half of that found at 5 micrograms/ml, although concentrations as high as 100 micrograms/ml have been used clinically to disinfect homografts. Scanning electron microscopy (SEM) also confirmed the extensive loss of endothelium after exposure to high concentrations of amphotericin B. Our study suggests that the other four antibiotics used in the concentrations described above do not damage endothelial function; amphotericin B is also harmless if used at a concentration of 5 micrograms/ml.
Subject(s)
Anti-Bacterial Agents/pharmacology , Aortic Valve/drug effects , Amphotericin B/administration & dosage , Amphotericin B/pharmacology , Amphotericin B/toxicity , Animals , Anti-Bacterial Agents/administration & dosage , Aortic Valve/ultrastructure , Azlocillin/administration & dosage , Azlocillin/pharmacology , Bradykinin/pharmacology , Cell Survival/drug effects , Cloxacillin/administration & dosage , Cloxacillin/pharmacology , Dose-Response Relationship, Drug , Drug Combinations , Endothelium/drug effects , Endothelium/ultrastructure , Epoprostenol/biosynthesis , Gentamicins/administration & dosage , Gentamicins/pharmacology , Metronidazole/administration & dosage , Metronidazole/pharmacology , Microscopy, Electron, Scanning , Sterilization , Swine , Transplantation, HomologousABSTRACT
BACKGROUND: In-vitro and clinical efficacy of a combination therapy consisting of 3 antibiotic agents was to be assessed in neonatal septicemia. METHODS: From 1980 to 1987, 152 newborns with septicemia as proven by blood culture were treated with an initial antibiotic regimen consisting of azlocillin (150 mg/kg bw), cefotaxime (100 mg/kg bw), and tobramycin (5 mg/kg bw). RESULTS: According to the microbiologic testing, antimicrobic therapy was effective in each of the 152 organisms: 101/152 bacteria were susceptible to all 3 agents; resistance to 1 or 2 of the antibiotics was evident in 33/152 and in 18/152 organisms, respectively. Mortality due to septicemia was 7.2%. CONCLUSION: As no difference was observed in the frequency in which one of the three antibiotic substances was the only effective drug, each of the 3 agents seemed to be necessary for clinical effectiveness of this antibiotic combination.
Subject(s)
Azlocillin/administration & dosage , Cefotaxime/administration & dosage , Infant, Premature, Diseases/drug therapy , Sepsis/drug therapy , Tobramycin/administration & dosage , Bacteriological Techniques , Dose-Response Relationship, Drug , Drug Therapy, Combination/therapeutic use , Female , Humans , Infant, Newborn , Infant, Premature, Diseases/microbiology , Male , Microbial Sensitivity Tests , Risk Factors , Sepsis/microbiology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Streptococcal Infections/drug therapy , Streptococcal Infections/microbiology , Streptococcus agalactiae/drug effectsABSTRACT
A prospective, randomized trial comparing monotherapy with high-dose ciprofloxacin versus a standard combination regimen of azlocillin and netilmicin in the empirical treatment of febrile episodes in neutropenic patients was performed. One hundred and forty-six patient episodes were randomized, but ten (seven ciprofloxacin and three azlocillin/netilmicin) were considered unevaluable for efficacy, and three episodes were withdrawn due to incorrect randomization or non-neutropenia. Of the remaining 133 episodes, infections resolved without modification of therapy in 25/66 (38%) versus 28/67 (42%) of ciprofloxacin and azlocillin/netilmicin treated groups respectively (P = 0.72). Considering all randomized episodes, therapy was modified in 46/73 (63%) episodes with ciprofloxacin and 39/70 (56%) with azlocillin/netilmicin (P = 0.40). Of 73 patient episodes randomized to ciprofloxacin, 25 (34%) received oral follow-on therapy after a median of three days of intravenous therapy. Infections were microbiologically documented in 31/73 (42%) ciprofloxacin and 32/70 (46%) azlocillin/netilmicin, of which 8/27 (30%) and 14/31 (45%) of evaluable episodes resolved without modification of therapy respectively (P = 0.28). Gram-positive organisms accounted for 78% of all organisms cultured with 36% coagulase-negative staphylococci. Bacteriological eradication was recorded in 18/24 (75%) and 26/29 (90%) evaluable patient episodes treated with ciprofloxacin and azlocillin/netilmicin respectively (P = 0.27). Superinfections were seen in 14% of episodes in both groups, and subsequent infections in 12% ciprofloxacin and 14% azlocillin/netilmicin treated patients. Two patients (one ciprofloxacin and one azlocillin/netilmicin) died within 48 h of randomization, and a further 13 patients (four ciprofloxacin and nine azlocillin/netilmicin) died before resolution of neutropenia. Adverse events were recorded in 9% and 15% of ciprofloxacin and azlocillin/netilmicin treated patients respectively, with skin rash (five ciprofloxacin and four azlocillin/netilmicin), nephrotoxicity (two azlocillin/netilmicin), abnormal liver function tests (two azlocillin/netilmicin), ototoxicity (one azlocillin/netilmicin) and nausea (one ciprofloxacin) being the major events recorded. It was concluded that monotherapy with ciprofloxacin at this dosage is a safe alternative to combination therapy with azlocillin/netilmicin, and has the advantages of twice daily administration, iv and oral presentations, no cross allergy in beta-lactam-hypersensitive patients, and no nephro- or oto-toxicity.
Subject(s)
Azlocillin/therapeutic use , Ciprofloxacin/therapeutic use , Drug Therapy, Combination/therapeutic use , Fever/drug therapy , Netilmicin/therapeutic use , Neutropenia/complications , Adolescent , Adult , Aged , Azlocillin/administration & dosage , Azlocillin/adverse effects , Ciprofloxacin/administration & dosage , Ciprofloxacin/adverse effects , Double-Blind Method , Drug Therapy, Combination/administration & dosage , Drug Therapy, Combination/adverse effects , Female , Fever/complications , Humans , Male , Middle Aged , Netilmicin/administration & dosage , Netilmicin/adverse effectsABSTRACT
The effect of dose scheduling on the pharmacodynamics of simulated human doses of ciprofloxacin (200 mg intravenously [iv] every 12 h) and azlocillin (4 g iv every 12 h) alone or in combination against Pseudomonas aeruginosa was studied in a two-compartment in vitro kinetic model of infection. Studies with the two drugs in combination were compared using simultaneous or staggered (first doses of each drug were administered 6 h apart) dosing schedules. Bacterial regrowth and resistance were prevented by all combination dosing schedules; however, the simultaneous regimen consistently provided the greatest extent of killing for all strains, particularly in those initially resistant to ciprofloxacin. These enhanced effects of the combination were corroborated by an increase in the peak and duration of bactericidal activity in the analogous "serum" compartment of the model. These data show the potential usefulness of simultaneous dosing of an antipseudomonal beta-lactam with ciprofloxacin against P. aeruginosa.
Subject(s)
Azlocillin/pharmacology , Ciprofloxacin/pharmacology , Pseudomonas aeruginosa/drug effects , Azlocillin/administration & dosage , Azlocillin/pharmacokinetics , Ciprofloxacin/administration & dosage , Ciprofloxacin/pharmacokinetics , Drug Resistance, Microbial , Drug Therapy, Combination , Models, Biological , Pseudomonas aeruginosa/growth & development , Time FactorsABSTRACT
The pharmacodynamics of amikacin given as a single daily dose was compared with standard divided dosing in an in-vitro model of infection. This model allows the exposure of log phase bacteria to changing concentrations of antibiotics that simulate the kinetics of the drugs in human patients. Two strains of Pseudomonas aeruginosa, one sensitive and one resistant to azlocillin were studied (MICs for amikacin were 16 and 8 mg/l respectively). Simulated drug regimens included: amikacin 400 mg q 8 h; amikacin 1.2 g q 24 h; and azlocillin 4 g q 12 h. Each regimen alone and both combinations of amikacin plus azlocillin were studied. With both amikacin regimens initial rapid killing was followed by regrowth of resistant subpopulations. Azlocillin alone produced minimal killing of the resistant strain and moderate killing with ultimate bacteriostasis of the susceptible strain. Bacterial regrowth was prevented with both combination regimens with the single daily dose of amikacin plus azlocillin producing the most rapid and complete killing, especially of the azlocillin resistant strain. These data support further clinical studies of single daily dosing of aminoglycosides.
Subject(s)
Amikacin/administration & dosage , Azlocillin/administration & dosage , Pseudomonas aeruginosa/drug effects , Amikacin/pharmacology , Azlocillin/pharmacology , Drug Resistance, Microbial , Drug Therapy, Combination/administration & dosage , Drug Therapy, Combination/pharmacology , Microbial Sensitivity TestsABSTRACT
Charts were reviewed for 63 patients whose chronic pseudomonas osteomyelitis was treated with high doses of extended-spectrum penicillins for prolonged periods. The incidence of untoward drug reactions was significantly higher than expected. Carbenicillin evoked adverse reactions in 22.8% of patients. However, most of these reactions were mild, and a change of drug was required in only 5.7% of cases. No adverse drug reactions were observed with cumulative doses of less than 750 g. In contrast to carbenicillin, the ureidopenicillins were associated with adverse reactions in 67.7% of patients; most reactions were moderate to severe in intensity; a cumulative dose of greater than 250 g produced adverse reactions; and discontinuation or change of therapy was required in 51.6% of cases. The main adverse reactions to both carbenicillin and the ureidopenicillins included rash, drug fever, leukopenia, eosinophilia, thrombocytopenia, and hepatic damage.
Subject(s)
Azlocillin/adverse effects , Carbenicillin/adverse effects , Mezlocillin/adverse effects , Piperacillin/adverse effects , Pseudomonas Infections/drug therapy , Adult , Aged , Aged, 80 and over , Azlocillin/administration & dosage , Azlocillin/therapeutic use , Carbenicillin/administration & dosage , Carbenicillin/therapeutic use , Eosinophilia/chemically induced , Female , Humans , Leukopenia/chemically induced , Liver/drug effects , Male , Mezlocillin/administration & dosage , Mezlocillin/therapeutic use , Middle Aged , Osteomyelitis/drug therapy , Piperacillin/administration & dosage , Piperacillin/therapeutic use , Retrospective Studies , Thrombocytopenia/chemically inducedABSTRACT
The results of five consecutive prospective trials define the role of perioperative antibiotic prophylaxis in head and neck surgery. For contaminated head and neck cases and for endonasal sinus surgery, a single-dose prophylaxis seems to be sufficient. Most clean cases do not need antibiotic prophylaxis. Risk factors for wound infection include nicotine or alcohol abuse, poor oral hygiene and increasing age. Previous radiotherapy seems to be of minor importance.