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1.
J Antimicrob Chemother ; 76(7): 1840-1844, 2021 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-33975336

RESUMEN

BACKGROUND: Tetracyclines are widely used as oral therapy of MRSA infection, however, the pharmacodynamic underpinning is absent. OBJECTIVES: We employed an in vitro pharmacokinetic model to study the pharmacodynamics of minocycline alone and in combination with rifampicin. METHODS: An exposure-ranging design was used to establish fAUC/MIC targets for static, -1 log drop and -2 log drop effects against Staphylococcus aureus for minocycline and in combination with rifampicin. We then simulated 7-10 day human dosing of minocycline and the combination. RESULTS: The minocycline fAUC/MIC for 24 h static effect and -1 log drop in bacterial load were 12.5 ±â€Š7.1 and 23.3 ±â€Š12.4. fAUC/MIC targets for static and -1 log drop were greater at 48 and 72 h. The addition of simulated free rifampicin associated with dosing 300 mg q12h reduced the 24 h minocycline fAUC/MICs. Simulations performed over 7-10 days exposure indicated that for minocycline standard human doses there was a 1-3 log reduction in viable count and no changes in population profiles. Addition of rifampicin resulted in larger reductions in staphylococcal load but emergence of resistance to rifampicin. There was no resistance to minocycline. CONCLUSIONS: An fAUC/MIC minocycline target of 12-36 is appropriate for S. aureus. Addition of rifampicin decreases bacterial load but results in emergence of resistance to rifampicin. Unusually, there was no emergence of resistance to minocycline.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana , Minociclina/farmacología , Rifampin/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus
2.
J Antimicrob Chemother ; 76(3): 667-670, 2021 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-33294925

RESUMEN

BACKGROUND: The pharmacodynamics of omadacycline have been extensively studied against Gram-positive pathogens but less information is available for Gram-negative pathogens. We describe the pre-clinical pharmacodynamics of omadacycline against Escherichia coli and Acinetobacter baumannii. METHODS: An in vitro dilutional pharmacokinetic model was used. Exposure experiments with fAUC/MIC ratios ranging from 0 to 1200 were performed using five strains of E. coli and five strains of A. baumannii. Reduction in bacterial load and changes in population profiles were measured. RESULTS: The fAUC/MIC targets against E. coli for 24 h static and -1 log reduction in load were 25.3 ±â€Š17.2 and 42.7 ±â€Š32.5, respectively. For A. baumannii the fAUC/MIC for 24 h static effect was 108.1 ±â€Š38.6. Changes in population profiles were observed for E. coli at fAUC/MIC ratios of ≤200 and for A. baumannii up to 1200. MICs were increased 2-32 fold. CONCLUSIONS: fAUC/MIC targets for A. baumannii are greater than for E.coli and changes in population profiles more likely. E. coli fAUC/MIC targets align with in vivo data and will be useful in determining omadacycline dosing for this pathogen.


Asunto(s)
Acinetobacter baumannii , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Escherichia coli , Pruebas de Sensibilidad Microbiana , Tetraciclinas
4.
Lett Appl Microbiol ; 68(4): 294-302, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30770577

RESUMEN

Chronic osteomyelitis is difficult to treat, with biofilm growth and the diffusion barrier to antibiotics presented by bone contributory factors. The aim of this study was to develop and evaluate an in vitro model of osteomyelitis. A bioluminescent strain of Staphylococcus aureus was grown in bone blocks made from bovine femur. Light output was insufficient for detection of bacterial cells within bone by 24 h and viable counting of crushed bone blocks was used to determine bacterial survival. Challenge of 72 h biofilms with gentamicin and daptomycin for 24 h demonstrated that only concentrations of 10 times the clinical peak serum target levels (100 mg l-1 gentamicin and 1000 mg l-1 daptomycin) resulted in significant reductions in cell viability compared to controls. Once daily dosing over 7 days resulted in ≥3 log reductions in cell numbers by 48 h. Thereafter no significant reduction was achieved, although emergence of resistance was suppressed. Determination of antibiotic concentration in bone blocks over 7 days indicated that neither agent was able to consistently reach levels in bone of >10% of the original dose. The model was, therefore, able to demonstrate the challenges posed by biofilm growth on and within bone. SIGNIFICANCE AND IMPACT OF THE STUDY: The majority of studies of antibiotic efficacy in the treatment of chronic osteomyelitis are carried out in animals. We developed an in vitro model of Staphylococcus aureus infection of bone to evaluate the ability of antibiotics to eradicate mature biofilms on surfaces analogous to necrotic bone. The results demonstrated the difficulties which occur in osteomyelitis treatment, with only very high concentrations of antibiotic able to penetrate the bone sufficiently to reduce bacterial survival whilst still failing to eradicate biofilms. This model could be of use in initial screening of novel compounds intended for use in the treatment of osteomyelitis.


Asunto(s)
Antibacterianos/farmacología , Biopelículas/crecimiento & desarrollo , Daptomicina/farmacología , Gentamicinas/farmacología , Osteomielitis/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/crecimiento & desarrollo , Animales , Bovinos , Modelos Animales de Enfermedad , Fémur/microbiología , Pruebas de Sensibilidad Microbiana , Osteomielitis/microbiología
5.
J Antimicrob Chemother ; 68(5): 1130-8, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23361641

RESUMEN

OBJECTIVES: We aim to further define the impact of the mechanism of fluoroquinolone resistance and inoculum load on the pharmacodynamic effects of levofloxacin and moxifloxacin on Streptococcus pneumoniae. METHODS: The antibacterial effects of and emergence of resistance (EoR) to moxifloxacin (400 mg once daily) or levofloxacin (750 mg once daily or 500 mg twice daily) were compared using five S. pneumoniae strains containing no known resistance mechanisms, efflux resistance mechanisms, a parC mutation or parC and gyrA mutations, at high (10(8) cfu/mL) and low (10(6) cfu/mL) inocula. An in vitro pharmacokinetic model was used and simulations were performed over 96 h. After drug exposure, isolates were tested for the presence of efflux pumps and mutations in the quinolone resistance-determining regions. RESULTS: A high inoculum diminished the antibacterial effect of moxifloxacin and levofloxacin. Levofloxacin at both dosages produced EoR with all strains. Levofloxacin regimens with AUC/MIC ratios <100 produced EoR. Moxifloxacin produced EoR with the parC strain only. CONCLUSIONS: Levofloxacin dosing regimens with low AUC/MIC ratios select for efflux pump overexpression, leading to fluoroquinolone resistance. Levofloxacin dosing may select for gyrA mutations, inducing moxifloxacin resistance. These data confirm that a fluoroquinolone AUC/MIC ratio of >100 is required for prevention of EoR.


Asunto(s)
Antibacterianos/farmacología , Compuestos Aza/farmacología , Farmacorresistencia Bacteriana , Levofloxacino , Ofloxacino/farmacología , Quinolinas/farmacología , Streptococcus pneumoniae/efectos de los fármacos , Antibacterianos/farmacocinética , Compuestos Aza/farmacocinética , Carga Bacteriana , Fluoroquinolonas , Modelos Teóricos , Moxifloxacino , Mutación , Ofloxacino/farmacocinética , Quinolinas/farmacocinética , Selección Genética
7.
J Hosp Infect ; 62(4): 450-2, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16487627

RESUMEN

Finger rings increase surface bacterial counts. Although scrubbing reduces these (P=0.05), there are more bacteria under rings than on adjacent skin or the opposite hand. If rings are removed before scrubbing, bacterial counts are reduced but remain higher than on adjacent skin or the opposite hand. Ideally, finger rings should not be worn by theatre staff. However, if they are, they should be removed prior to scrubbing for surgical operations.


Asunto(s)
Dedos/microbiología , Desinfección de las Manos/métodos , Clorhexidina/análogos & derivados , Clorhexidina/uso terapéutico , Recuento de Colonia Microbiana , Desinfectantes/uso terapéutico , Humanos , Auxiliares de Cirugía
8.
Vet J ; 169(2): 276-80, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15727921

RESUMEN

The efficacy of a topical preparation containing 0.5% fusidic acid and 0.1% betamethasone-17-valerate was compared to a systemic therapy (comprising a combination of parenteral dexamethasone and oral clavulanate-potentiated amoxycillin) in the treatment of 104 dogs with acute moist dermatitis. Significant improvement was evident after seven days in both treatment groups in all clinical parameters assessed and there was no significant difference in the overall response between the two treatment groups. Staphylococcus intermedius was the most frequently isolated organism from swabs at the first visit (Day 0). No resistance to fusidic acid or clavulanate-potentiated amoxycillin was encountered. The study demonstrates no difference in the clinical improvement achieved in canine acute moist dermatitis following topical or systemic therapy and that both treatment regimes represent effective treatment options for the condition.


Asunto(s)
Antibacterianos/uso terapéutico , Antiinflamatorios/uso terapéutico , Betametasona/uso terapéutico , Dermatitis/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Ácido Fusídico/uso terapéutico , Administración Cutánea , Administración Oral , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Animales , Antibacterianos/administración & dosificación , Antiinflamatorios/administración & dosificación , Betametasona/administración & dosificación , Dermatitis/tratamiento farmacológico , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Enfermedades de los Perros/microbiología , Enfermedades de los Perros/patología , Perros , Inglaterra , Femenino , Ácido Fusídico/administración & dosificación , Geles , Masculino , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
9.
Int J Antimicrob Agents ; 22(6): 557-61, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14659651

RESUMEN

The activity of nine peptide deformylase (PDF) inhibitors undergoing clinical evaluation were compared with co-amoxiclav, levofloxacin, moxifloxacin, erythromycin and telithromycin against a range of respiratory and skin pathogens (n=166). The PDF inhibitor showed good activity against Streptococcus pneumoniae, Moxarella catarrhalis, Group A streptococci and Staphylococcus aureus irrespective of beta-lactam or fluoroquinolone susceptibility. Against Haemophilus influenzae, MIC(90) values were generally higher. BB-88488 was the most active compound. Overall these data suggest that PDF inhibitors are an interesting new class of antimicrobial worthy of further investigation in the treatment of respiratory tract and skin infections.


Asunto(s)
Amidohidrolasas/antagonistas & inhibidores , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/microbiología , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Enfermedades Cutáneas Bacterianas/microbiología , Bacterias/enzimología , Bacterias/patogenicidad , Farmacorresistencia Bacteriana , Humanos , Técnicas In Vitro , Pruebas de Sensibilidad Microbiana
10.
J Hosp Infect ; 52(1): 68-70, 2002 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12372329

RESUMEN

Twenty items of three jewellery types were studied. Finger rings, nose and ear piercings increased local surface bacterial counts when in situ, and especially after removal (P<0.0001). Although in the UK the National Association of Theatre Nurses' guidelines suggest that all jewellery should be removed before scrubbing, we suggest that jewellery worn on noses and ears should be left in situ and covered by masks and hats, respectively. The effect of jewellery on skin disinfection needs further study before guidelines can be made concerning finger rings.


Asunto(s)
Bacterias/aislamiento & purificación , Vestuario , Enfermeras y Enfermeros , Quirófanos , Piel/microbiología , Femenino , Humanos
11.
J Hosp Infect ; 50(4): 281-5, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12014901

RESUMEN

There is a paucity of data on the penetration of bacteria through surgical gowns during operations. A simple new method was developed, using Petri dishes filled with horse blood agar that were attached to the outside of the gown material. This was used to assess bacterial penetration through disposable spun-bonded polyester gowns and re-usable woven polyester gowns during normal use. There was a significant difference between the two gown types when tested in the axilla (P = 0.02), the groin (P = 0.02) and the peri-anal region (P < 0.01), with the disposable gowns performing to a higher standard. Re-usable gowns demonstrated variation in penetrability, and for this reason, may be unsuitable for use in orthopaedic implant surgery.


Asunto(s)
Bacterias/aislamiento & purificación , Contaminación de Equipos , Ropa de Protección/microbiología , Equipos Desechables/microbiología , Humanos , Quirófanos
12.
J Antimicrob Chemother ; 49(3): 535-9, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11864955

RESUMEN

The in vitro potency of BAL 9141, a new pyrrolidinone cephalosporin, was tested against non-duplicate strains of anaerobic bacteria. The MIC(50) was 1 mg/L against Actinomyces species, Clostridium species, Gram-positive anaerobic cocci, Porphyromonas species, Fusobacterium species, Lactobacillus species, Prevotella species and Veillonella species. The MIC(50) was 16 mg/L for Bacteroides fragilis and other Bacteroides species. BAL 9141 was not active against cefoxitin-resistant Bacteroides fragilis.


Asunto(s)
Bacterias Anaerobias/efectos de los fármacos , Cefalosporinas/farmacología , Lactamas/farmacología , Penicilinas/farmacología , Tienamicinas/farmacología , Bacterias Anaerobias/aislamiento & purificación , Farmacorresistencia Bacteriana
15.
J Antimicrob Chemother ; 48(5): 727-30, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11679564

RESUMEN

Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) may account for treatment failure with vancomycin and act as a precursor of vancomycin-intermediate or -resistant S. aureus. The activity of vancomycin was assessed against vancomycinsusceptible, hVISA and VISA strains in a dilutional pharmacokinetic model. Over a 48 h period, total bacteria and cells with a vancomycin-intermediate phenotype were quantified. Total counts of hVISA were reduced by vancomycin in a similar way to a vancomycin-susceptible control. The vancomycin-intermediate sub-population was eradicated from the model within one dose interval. Exposure to low vancomycin concentrations did not result in an increase in the proportion of cells which were vancomycin intermediate. Short-term exposure of hVISA to vancomycin at gradient concentrations did not increase the proportion of cells with vancomycin-intermediate phenotype.


Asunto(s)
Antibacterianos/farmacocinética , Resistencia a la Meticilina , Staphylococcus aureus/efectos de los fármacos , Vancomicina/farmacocinética , Antibacterianos/farmacología , Recuento de Colonia Microbiana/métodos , Humanos , Resistencia a la Meticilina/genética , Pruebas de Sensibilidad Microbiana , Vancomicina/farmacología
16.
Antimicrob Agents Chemother ; 45(10): 2916-21, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11557490

RESUMEN

The pharmacodynamics of gemifloxacin against Streptococcus pneumoniae were investigated in a dilutional pharmacodynamic model of infection. Dose fractionation was used to simulate concentrations of gemifloxacin in human serum associated with 640 mg every 48 h (one dose), 320 mg every 24 h (two doses), and 160 mg every 12 h (four doses). Five strains of S. pneumoniae for which MICs were 0.016, 0.06, 0.1, 0.16, and 0.24 mg/liter were used to assess the antibacterial effect of gemifloxacin. An inoculum of 10(7) to 10(8) CFU/ml was used, and each experiment was performed at least in triplicate. The pharmacodynamic parameters (area under the concentration-time curve [AUC]/MIC, maximum concentration of drug in serum [C(max)]/MIC, and the time that the serum drug concentration remains higher than the MIC [T > MIC]) were related to antibacterial effect as measured by the area under the bacterial-kill curve from 0 to 48 h (AUBKC(48)) using an inhibitory sigmoid E(max) model. Weighted least-squares regression was used to predict the effect of the pharmacodynamic parameters on AUBKC(48), and Cox proportional-hazards regression was used to predict the effect of the three pharmacodynamic parameters on the time needed to kill 99.9% of the starting inoculum (T99.9). There was a clear relationship between strain susceptibility and clearance from the model. The simulations (160 mg every 12 h) were associated with slower initial clearance than were the other simulations; in contrast, bacterial regrowth occurred with the 640-mg simulation when MICs were > or =0.1 mg/liter. The percentage coefficient of variance was 19% for AUBKC(48), and the inhibitory sigmoid E(max) model best fit the relationship between AUBKC(48) and AUC/MIC. C(max)/MIC and T > MIC fit less well. The maximum response occurred at an AUC/MIC of >300 to 400. In weighted least-squares regression analysis, there was no evidence that C(max)/MIC was predictive of AUBKC(48), but both AUC/MIC and T > MIC were. A repeat analysis using only data for which the T > MIC was >75% and for which hence regrowth was minimized indicated that AUC/MIC alone was predictive of AUBKC(48). Initial univariate analysis indicated that all three pharmacodynamic parameters were predictive of T99.9, but in the multivariate model only C(max)/MIC reached significance. These data indicate that gemifloxacin is an effective antipneumococcal agent and that AUC/MIC is the best predictor of antibacterial effect as measured by AUBKC(48). However, C(max)/MIC is the best predictor of speed of kill, as measured by T99.9. T > MIC also has a role in determining AUBKC(48), especially when the dose spacing is considerable. Once-daily dosing seems most suitable for gemifloxacin.


Asunto(s)
Antiinfecciosos/farmacología , Fluoroquinolonas , Naftiridinas/farmacología , Streptococcus pneumoniae/efectos de los fármacos , Recuento de Colonia Microbiana , Gemifloxacina , Humanos , Pruebas de Sensibilidad Microbiana
17.
J Antimicrob Chemother ; 45(2): 247-50, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10660511

RESUMEN

Meropenem administered as a single iv 3 g dose once every 24 h was used to treat nine ambulatory patients with infective exacerbations of bronchiectasis. Serum meropenem concentrations were measured before dosing and at 30 min after each 30 min infusion. Mean pre-dose concentrations were <0.1 mg/L and mean post-dose concentrations 93.9 +/- 29.5 mg/L (95% confidence interval (CI) 86. 2-101.6, n = 59). A pathogen was cultured from sputum in six patients and eradicated (<100 cfu/g sputum) in all but one by day 6 of therapy. Previous work on animals has shown that a bacteriostatic effect is seen with meropenem when t > MIC is greater than 20-30% of the dose interval. In these nine patients, this could be achieved and was associated with successful outcome for pathogens for which MICs are

Asunto(s)
Bronquiectasia/complicaciones , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/etiología , Tienamicinas/uso terapéutico , Anciano , Bronquiectasia/microbiología , Femenino , Infecciones por Haemophilus/tratamiento farmacológico , Infecciones por Haemophilus/microbiología , Haemophilus influenzae , Semivida , Humanos , Masculino , Meropenem , Persona de Mediana Edad , Infecciones Neumocócicas/tratamiento farmacológico , Infecciones Neumocócicas/microbiología , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Infecciones del Sistema Respiratorio/microbiología
18.
J Antimicrob Chemother ; 44(6): 761-6, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10590276

RESUMEN

The serum concentrations associated with the oral administration of 400 mg moxifloxacin every 24 h over 48 h in man were simulated in an in-vitro dilutional, continuous bacterial culture model of infection. The initial inoculum was 5 x 10(7)-5 x 10(8) cfu/mL and all strains were tested on at least three occasions. Two strains of Staphylococcus aureus (one methicillin susceptible, the other resistant) with moxifloxacin MICs 0.14 mg/L and 0.06 mg/L and two strains of beta-haemolytic streptococci, Lancefield Group A, MIC 0. 16 mg/L and Group G, MIC 0.4 mg/L were used. In addition, two laboratory-generated mutants with raised moxifloxacin MICs were also employed: methicillin-sensitive S. aureus (MSSA) MIC 1.0 mg/L and Group A streptococcus MIC 1.8 mg/L. The antibacterial effect of moxifloxacin was judged by changes in viable count over time, and the area under the bacterial-kill curve (AUBKC) after 24 and 48 h. For S. aureus MIC 0.14 mg/L the AUBKC(24) (log cfu/mL.h) was 77.8 +/- 4.6 and AUBKC(48) 92.0 +/- 6.9. For its mutant, moxifloxacin MIC 1.0 mg/L, the AUBKC(24) was 116.1 +/- 15.6 and AUBKC(48) 211.9 +/- 23.1, indicating decreased killing. AUBKC(24) and AUBKC(48) values of 110.7 +/- 10.3 and 130.9 +/- 21.3, respectively, were noted for the MRSA strain. The Group A streptococcus, MIC 0.16 mg/L, had an AUBKC(24) of 91.4 +/- 19.4 and AUBKC(48) of 157.0 +/- 70.9. The mutant, MIC 1.8 mg/L, had an AUBKC(24) of 127.0 +/- 1.9 and AUBKC(48) of 205.1 +/- 6.4. Despite a lower MIC (0.4 mg/L) the single strain of Group G streptococcus tested was killed poorly, AUBKC(24) 139.9 +/- 3.6 and AUBKC(48) 252.3 +/- 18.6. The pharmacodynamic parameters AUC/MIC, T > MIC, (AUC > MIC)/MIC (AUC = area under the curve, T = time) and WAUC ((AUC/MIC) (T > MIC/100)) (WAUC = weighted area under the curve) were related to AUBKC(24) and AUBKC(48) using an inhibitory sigmoid E(max) model. T > MIC was poorly related to AUBKC (r = 0.36) while AUC/MIC, (AUC > MIC)/MIC and WAUC were strongly related to AUBKC(24) (r = 0.75-0.79) and AUBKC(48) (r = 0.78-0.84). The maximum antibacterial effect was achieved with an AUC/MIC ratio of 150-200. AUC-related pharmacodynamic parameters predicted antibacterial effect better than T > MIC.


Asunto(s)
Antiinfecciosos/farmacología , Compuestos Aza , Fluoroquinolonas , Quinolinas , Staphylococcus aureus/efectos de los fármacos , Streptococcus pyogenes/efectos de los fármacos , Streptococcus/efectos de los fármacos , Antiinfecciosos/administración & dosificación , Antiinfecciosos/farmacocinética , Recuento de Colonia Microbiana , Medios de Cultivo , Humanos , Pruebas de Sensibilidad Microbiana , Moxifloxacino , Staphylococcus aureus/crecimiento & desarrollo , Streptococcus/crecimiento & desarrollo , Streptococcus pyogenes/crecimiento & desarrollo
19.
J Antimicrob Chemother ; 44(4): 445-53, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10588304

RESUMEN

The in-vitro activity of HMR 3647 and seven comparators (azithromycin, clarithromycin, erythromycin A, roxithromycin, penicillin G, ciprofloxacin and levofloxacin) were tested against 207 Streptococcus pneumoniae and 200 beta-haemolytic streptococci. Ten comparators (azithromycin, clarithromycin, erythromycin A, roxithromycin, ampicillin, co-amoxiclav, cefuroxime, cefotaxime, ciprofloxacin and levofloxacin) were tested against 143 Haemophilus influenzae and 58 Moraxella catarrhalis. The MIC50 of HMR 3647 for S. pneumoniae was < or =0.008 mg/L, less than that for the macrolides or quinolones tested. Pneumococci with an erythromycin A MIC of 0.06 mg/L (n = 23) had an MIC50 of HMR 3647 < or =0.008 mg/L, whereas isolates with an erythromycin A MIC > or =1 mg/L (n = 34) had an MIC50 of HMR 3647 of 0.03 mg/L, a four-fold increase. In contrast, the difference in macrolide MIC50s for the two groups was > or =64-fold. The MIC50s foro beta-haemolytic streptococci, classified by Lancefield group, were in the range 0.015 to 0.06 mg/L for HMR 3647. H. influenzae were categorized into three groups according to cefuroxime MIC: <1 mg/L (n = 72); 2-4 mg/L (n = 29); and >4 mg/L (n = 42). The MIC50 of HMR 3647 increased two-fold with increasing cefuroxime MICs; beta-lactam MICs increased much more markedly. The MIC50 of HMR 3647 for M. catarrhalis was 0.03 mg/L. HMR 3647 has good activity against respiratory tract pathogens but in-vitro susceptibility is affected by erythromycin A susceptibility in S. pneumoniae and beta-haemolytic streptococci.


Asunto(s)
Antibacterianos/farmacología , Haemophilus influenzae/efectos de los fármacos , Cetólidos , Macrólidos , Moraxella catarrhalis/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus/efectos de los fármacos , Farmacorresistencia Microbiana , Humanos , Pruebas de Sensibilidad Microbiana
20.
J Antimicrob Chemother ; 44(5): 661-7, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10552983

RESUMEN

The pharmacodynamics of ciprofloxacin were explored in an in-vitro continuous bacterial culture model of infection, by simulating two oral dosing regimens; 0.5 g 12-hourly (bd) and 1 g 24-hourly (od). Three strains of Escherichia coli (ciprofloxacin MICs 0.03, 0.5 and 2 mg/L); two strains of Pseudomonas aeruginosa (MICs 0.09 and 1.5 mg/L), two strains of Staphylococcus aureus (MICs 0.12 and 1 mg/L) and two strains of Streptococcus pneumoniae (MICs 0.5 and 2 mg/L) were used. Three pharmacodynamic parameters, T > MIC, C(max)/MIC and AUC/MIC (T = time, C(max) = peak serum concentration, AUC = area under the curve), were compared with area under the bacterial-kill curve (AUBKC) (after transformation of the AUBKC) using a simple E(max) or sigmoidal E(max) model. AUBKC was taken to be the main antibacterial effect measure. The models were compared by inspection of residuals and Akaike information criterion. E(max) models adequately described the relationship between AUC/MIC and AUBKC and between C(max)/MIC and AUBKC, but not between T> MIC and AUBKC. All three pharmacodynamic parameters are related to each other but multiple regression analysis indicated that AUC/MIC was the best individual predictor of AUBKC. Despite this, comparison of od and bd regimens indicates some advantage to od in terms of early antibacterial effect. Serum concentration-time curve shape has some importance in determining antibacterial effect. These data indicate that for ciprofloxacin AUC/MIC ratio is not the sole determinant of antibacterial effect.


Asunto(s)
Antiinfecciosos/administración & dosificación , Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Ciprofloxacina/administración & dosificación , Ciprofloxacina/farmacología , Área Bajo la Curva , Infecciones Bacterianas/microbiología , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Humanos , Pruebas de Sensibilidad Microbiana , Modelos Biológicos , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/crecimiento & desarrollo
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