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M J Robbins

Publications and source records attributed to M J Robbins.

At least 37 records · Page 2Linked to original sources

An in vitro characterization of cefditoren, a new oral cephalosporin.

Cefditoren (ME 1206) is a new cephalosporin available for oral administration as the pivaloyloxymethyl ester (ME 1207). The effect of medium formulation. pH, cation concentration and inoculum on the in vitro activity of cefditoren was investigated prior to determining its comparative antibacterial potency against a wide range of clinical bacterial isolates, its bactericidal activity against susceptible strains and the duration of its post-antibiotic effect (PAE). Cefditoren was shown to possess a broad-spectrum of cidal antibacterial activity against both Gram-positive and Gram-negative species with stability to many beta-lactamases of clinical importance. Its activity against Gram-positive species was similar to augmentin and cefuroxime, but superior to that of cefaclor and cefixime, while its beta-lactamase stability was similar to that of cefixime and ceftazidine, characterizing it as a third generation cephalosporin. Investigation of the effect of laboratory variables on the in vitro activity of cefditoren indicates that it will present no special problems when tested in the clinical setting against bacterial pathogens. PAE of 0.9 h, or greater, for Staphylococcus spp, Streptococcus pneumoniae and Moraxella catarrhalis may support the use of an extended dose-interval when cefditoren is used for the treatment of respiratory tract infections.

Bacteria↗

The in vitro activity of some 14-, 15- and 16- membered macrolides against Staphylococcus spp., Legionella spp., Mycoplasma spp. and Ureaplasma urealyticum.

Erythromycin is a macrolide antimicrobial chemically comprised of a 14-membered lactone ring substituted with a neutral (cladinose) and an amino (desosamine) sugar. Recently, a number of new macrolide molecules have been identified containing either 14-, 15- or 16-membered substituted lactone rings. In this study the authors have determined the in vitro activity of roxithromycin and clarithromycin (both 14-membered macrolides), azithromycin (a 15-membered macrolide or azalide) and midecamycin acetate (a 16-membered macrolide) against clinical isolates of Staphylococcus spp., (including methicillin-susceptible and -resistant isolates), Legionella spp., Mycoplasma spp. and Ureaplasma urealyticum. Minimum inhibitory concentrations of the macrolides for the clinical isolates of Staphylococcus spp. examined were widely distributed. However, midecamycin acetate retained activity against those isolates of Staphylococcus spp. exhibiting inducible resistance to erythromycin and the other macrolides tested. Isolates characterised by constitutive resistance to erythromycin were also resistant to midecamycin acetate. All of the macrolides were very active against Legionella spp., with clarithromycin demonstrating the greatest potency (MIC range: less than or equal to 0.03-0.06 mg/l). Isolates of Mycoplasma pneumoniae and Ureaplasma urealyticum were susceptible to all of the macrolides tested. However, erythromycin, roxithromycin, clarithromycin and azithromycin were poorly active against isolates of Mycoplasma hominis. By contrast, the same isolates were susceptible (MIC range: 0.008-0.12 mg/l) to midecamycin acetate.

Anti-Bacterial Agents↗

Comparative in vitro activity of ciprofloxacin and other unrelated antimicrobials against bacterial respiratory tract pathogens.

Ciprofloxacin is a new fluorinated 4-quinolone with a broad spectrum of antimicrobial activity which includes both Gram-negative and Gram-positive bacteria. In this study the in vitro activity of ciprofloxacin has been determined against bacteria associated with respiratory tract infections and compared with that of other antimicrobial agents used in the therapy of such infections. Ciprofloxacin (MIC90 0.008 mg/l) was highly active against Haemophilus influenzae, including isolates producing beta-lactamase which were resistant to amoxycillin. Ciprofloxacin (MIC90 0.06 mg/l) was also highly active against Branhamella catarrhalis, again including those isolates resistant to amoxycillin as a result of beta-lactamase production. Isolates of Streptococcus pneumoniae were less susceptible to ciprofloxacin (MIC90 2 mg/l) but were highly susceptible to amoxycillin (MIC90 less than 0.12 mg/l) and erythromycin (MIC90 0.25 mg/l). Isolates of Klebsiella aerogenes were highly susceptible to ciprofloxacin (MIC90 0.06 mg/l) but much less so to amoxycillin, sulfamethoxazole, trimethoprim, oxytetracycline and erythromycin. Ciprofloxacin (MIC90 0.5 mg/l) was very active against Staphylococcus aureus, including those isolates resistant to amoxycillin and flucloxacillin, and against Mycoplasma pneumoniae. Together with rifampicin and erythromycin, ciprofloxacin was highly active against Legionella pneumophila (MIC90 0.015 mg/l). These results suggest that clinical evaluation of ciprofloxacin in the treatment of respiratory tract infections is justified.

Anti-Bacterial Agents↗

The comparative in-vitro activity of ofloxacin.

The antibacterial activity of ofloxacin, a new fluoroquinolone, was evaluated against a wide range of clinical bacterial isolates and compared with that of nalidixic acid, norfloxacin, enoxacin, pefloxacin and ciprofloxacin by determination of minimum inhibitory concentrations (MICs). Ofloxacin was very active against nalidixic acid-susceptible isolates of the Enterobacteriaceae (MIC less than or equal to 0.12 mg/l) and was also active against strains resistant to nalidixic acid (MIC less than or equal to 2 mg/l). The activity was similar to norfloxacin, enoxacin and pefloxacin but some four-fold less than that of ciprofloxacin. All of the fluoroquinolones were highly active against Vibrio cholerae (MIC less than or equal to 0.015 mg/l), V. parahaemolyticus (MIC less than or equal to 0.12 mg/l) Aeromonas hydrophila (MIC less than or equal to 0.03 mg/l), Plesiomonas shigelloides (MIC less than or equal to 0.015 mg/l), Campylobacter jejuni (MIC less than or equal to 0.5 mg/l), Neisseria spp., Haemophilus influenzae, H. ducreyi, Bordetella pertussis and Legionella pneumophila (MIC less than or equal to 0.06 mg/l for all species). Ofloxacin, ciprofloxacin and pefloxacin (MIC less than or equal to 1, 2 and 2 mg/l, respectively) showed similar activity against Staphylococcus spp. and were somewhat more active than enoxacin (MIC less than or equal to 4 mg/l) and norfloxacin (MIC less than or equal to 8 mg/l). Ofloxacin was moderately active against beta-haemolytic Streptococcus spp. (MIC less than or equal to 2 mg/l), Corynebacterium diphtheriae (MIC less than or equal to 1 mg/l) and Cory. jeikeium (MIC less than or equal to 2 mg/l) and somewhat less active against alpha- and non-haemolytic Streptococcus spp., Str. pneumoniae and Listeria monocytogenes (MIC less than or equal to 4 mg/l for all species) and Str. faecalis (MIC less than or equal to 8 mg/l). The activity of ofloxacin, against these species, was similar to ciprofloxacin and four to eight times greater than norfloxacin, enoxacin and pefloxacin. Ofloxacin, and all of the fluoroquinolones, were less active against anaerobic than aerobic bacteria. Clostridium perfringens (MIC less than or equal to 1 mg/l) was more susceptible to ofloxacin than were other anaerobic species and Cl. difficile (MIC less than or equal to 16 mg/l) was more resistant. Ofloxacin was the most active compound tested against Chlamydia trachomatis SA2f (MIC less than or equal to 0.5 mg/l) with only ciprofloxacin (MIC less than or equal to 1 mg/l) approaching similar activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria, Anaerobic↗

Precordial T-wave polarity changes in acute inferior infarction. A poor indicator of associated disease of the left anterior descending coronary artery.

T-wave polarity in V1 to V3 was examined in 70 patients with acute inferior wall myocardial infarctions (IWMI) as an indicator of significant disease in the left anterior descending coronary artery (LAD). Fifty-three percent (37/70) had precordial T-wave inversions, and of these 38 percent (14/37) had angiographically significant LAD disease. Conversely, 47 percent (33/70) had upright T waves in V1 to V3, and of these, 52 percent (17/33) had significant LAD disease. Likewise, 41 percent of the patients with ST segment depression in V1 to V3 had significant LAD disease, while 50 percent of those with isoelectric ST segments were similarly affected. Finally only 39 percent of those patients with both precordial ST segment depression and T-wave inversion had significant LAD disease. We conclude that neither anterior ST depression, T-wave inversion, nor a combination of both is a sensitive or specific indicator of LAD disease in patients with acute IWMI.

Aged↗

In vitro activity of vancomycin and teicoplanin against anaerobic bacteria.

The in vitro activity of vancomycin and teicoplanin, a new glycopeptide antimicrobial, was determined against a total of 286 anaerobic bacteria including Bacteroides fragilis group (100), B. melaninogenicus (21), B. bivius (16), Fusobacterium spp. (15), Peptococcus spp. (20), Peptostreptococcus spp. (21), Clostridium perfringens (23), C. difficile (41) and Propionibacterium acnes (29). Minimum inhibitory concentrations (MIC) were determined using an antimicrobial incorporation technique in Wilkins-Chalgren agar approximately 10(4) colony forming units (cfu) contained in 10 microliters Wilkins-Chalgren broth, which was applied to the surface of the agar plates using a multipoint inoculator. Following inoculation, plates were incubated for 48 h at 37 degrees C in an anaerobic atmosphere. Both vancomycin and teicoplanin were highly active against all the Gram-positive anaerobic bacteria examined, 90% of all isolates being inhibited by 0.5 micrograms/ml of either antimicrobial. Isolates of B. fragilis group and Fusobacterium spp. were resistant to vancomycin (MIC90 64 micrograms/ml) and teicoplanin (MIC90 128 micrograms/ml). Unexpectedly, isolates of B. melaninogenicus and B. bivius which were resistant to vancomycin (MIC90 64 and 128 micrograms/ml respectively) were sensitive to teicoplanin (MIC90 2 and 2 micrograms/ml respectively).

Bacteria, Anaerobic↗

The effect of carbon dioxide on the in vitro activity of erythromycin and RU-28965 against anaerobic bacteria.

The in vitro activity of erythromycin and RU-28965 (a novel macrolide antimicrobial with improved pharmacokinetics) was determined against a variety of anaerobic bacteria in anaerobic atmospheres with and without added carbon dioxide. Minimum inhibitory concentrations (MIC) were determined using an antimicrobial incorporation technique in Wilkins-Chalgren agar (Oxoid, UK) containing saponinlysed horse blood to a final concentration of 10%. The inoculum used was approximately 10(4) colony forming units (cfu) contained in 10 microliters Wilkins-Chalgren broth, which was applied to the surface of the agar plates using a multipoint inoculator. Following inoculation, plates were incubated for 48 h at 37 degrees C in an anaerobic atmosphere containing 10% carbon dioxide or in hydrogen alone. The MIC of each antimicrobial for each organism examined was determined as the lowest concentration of the antimicrobial which completely inhibited growth of the inoculum. The minimum concentrations required to inhibit the growth of 50% (MIC50) and 90% (MIC90) of the bacteria examined were also determined. The MICs of erythromycin and RU-28965 for isolates of the Bacteroides fragilis group, B. bivius and Fusobacterium spp. were generally 10-100 times greater when determined in the presence of carbon dioxide than when determined in hydrogen alone. The MICs of erythromycin and RU-28965 for B. melaninogenicus, Peptococcus spp., Peptostreptococcus spp., Clostridium perfringens, Cl. difficile and Propionibacterium acnes were less affected by the presence of carbon dioxide.

Anaerobiosis↗

In vitro activity of aztreonam, cefuroxime and ceftazidime against gram-negative rods isolated from hospital patients with urinary tract infection.

The in vitro activity of aztreonam, cefuroxime and ceftazidime was determined against 2,372 Gram-negative rods (including Pseudomonas spp.) isolated from hospital patients with urinary tract infections during 1985. Minimum inhibitory concentrations (MICs) were determined using an agar incorporation technique in Mueller-Hinton agar. The inoculum used was approximately 10(5) colony forming units (cfu) contained in 10 microliter Mueller-Hinton broth, which was applied to the surface of the agar plates using a multipoint inoculator. Following inoculation plates were incubated aerobically at 37 degrees C for 18 h. The MIC of each antimicrobial for each organism examined was determined as the lowest concentration of the antimicrobial which completely inhibited growth of the inoculum. The minimum concentration required to inhibit the growth of 90% (MIC90) of the bacterial isolates in each genus or species examined was also determined. In general the antibacterial spectrum of aztreonam was comparable to that of ceftazidime and superior to that of cefuroxime. Against Escherichia coli, which accounted for 72% of the isolates examined, aztreonam (MIC90 less than or equal to 0.25 microgram/ml) was slightly more active than ceftazidime (MIC90 0.5 microgram/ml) and considerably more active than cefuroxime (MIC90 8 micrograms/ml). Aztreonam was active against Pseudomonas spp. (MIC90 16 micrograms/ml), although somewhat less so than ceftazidime (MIC90 4 micrograms/ml). Cefuroxime showed low activity against this genus (MIC90 greater than 128 micrograms/ml).

Anti-Bacterial Agents↗

Infective endocarditis: a pathophysiologic approach to therapy.

The treatment of infective endocarditis requires a multidisciplinary approach, including the expertise of cardiologists, infectious disease specialists, and cardiothoracic surgeons. By drawing from the pathophysiology, this article discusses a multidimensional approach to the treatment of these difficult patients.

Anti-Bacterial Agents↗

Right-sided valvular endocarditis: etiology, diagnosis, and an approach to therapy.

Right- and left-sided endocarditis are two distinct entities, both clinically and experimentally. As such, they require different clinical approaches. The accurate diagnosis of right-sided endocarditis rests largely on a high index of suspicion which is often raised in the case of an intravenous drug abuser with fever, especially when pulmonary infiltrates are detected. Two-dimensional echocardiography can be expected to confirm the diagnosis in approximately 80% of the cases. Measurement of the echocardiographically visualized vegetation provides both prognostic and therapeutic information. When the vegetation is less than 1.0 cm in diameter, antibiotic therapy can be reasonably expected to cure the infection. Despite a prolonged fever, we recommend continued medical management in these cases, as lack of response to medical management is almost exclusively seen in cases in which echocardiographically determined vegetation size is greater than or equal to 1.0 cm, perhaps because of the slower metabolic rate of bacterial colonies within these large vegetations. If, however, after 3 weeks of antibiotic therapy, fevers persist in a patient in whom two-dimensional echocardiography reveals a vegetation of greater than or equal to 1.0 cm, surgical intervention should be contemplated. Prior to such intervention, the physician must be careful to exclude other sources of fever, such as abscesses, phlebitis, and drug reactions, as indicated in Table III. Also, adequate antibiotic levels should be documented prior to surgical intervention. Because of the adverse effect on vegetation size upon the response to antibiotics, there may be a role for anticoagulation in order to potentiate the effects of the antibiotic therapy; however, this is purely speculative at present.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

Influence of vegetation size on clinical outcome of right-sided infective endocarditis.

Endocarditis involving right-sided valvular structures is largely a disease of intravenous drug abusers. The majority of these patients respond to antibiotic therapy with clearing of their bacteremia and preservation of their hemodynamic status. This study evaluated the prognostic value of echocardiographically determined vegetation size in 23 episodes of right-sided valvular endocarditis in 21 patients. Right-sided vegetations were visualized in 19 of 23 episodes (83 percent). Of these, a vegetation of 1.0 cm or greater was found in 11. No patient with an echocardiographically determined vegetation size of less than 1.0 cm required surgery, whereas four of 11 (36 percent) of those episodes in which the vegetation size was 1.0 cm or greater required surgery for persistent pyrexia (p less than 0.05). In all patients requiring surgery, a bioprosthetic tricuspid valve was placed at the time of initial surgery and in no patient did early reinfection occur. This study reconfirms the benign prognosis of right-sided valvular endocarditis. Further, although vegetations of less than 1.0 cm identify those patients who will respond to medical therapy, echocardiographically documented vegetations of 1.0 cm or greater are associated with a significantly lower response rate to appropriate medical therapy. The association of fever that persists for more than three weeks in the absence of another source of infection with an echocardiographically demonstrable right-sided vegetation of 1 cm or more identifies those patients who will require surgical intervention. Finally, tricuspid valve replacement can be performed at the time of initial surgery without undue concern for early reinfection or valve dysfunction.

Adult↗

Comparative in vitro studies with 4-quinolone antimicrobials.

The minimal inhibitory concentrations (MICs) of nalidixic acid, pipemidic acid, cinoxacin, oxolinic acid, flumequine, pefloxacin, acrosoxacin, amifloxacin, norfloxacin, enoxacin, ofloxacin and ciprofloxacin were determined for a range of clinical isolates. MICs were determined using an agar dilution technique in Mueller-Hinton agar supplemented with 10% lysed horse blood. The inoculum used was approximately 10(4) colony forming units, contained in 10 microliters Mueller-Hinton broth, which was applied to the agar plates using a multipoint inoculator. Following inoculation, plates were incubated in conditions appropriate for the organisms under investigation. The MIC of each antimicrobial for each isolate examined was determined as the lowest concentration of the antimicrobial which completely inhibited growth of the inoculum. The minimum concentrations required to inhibit the growth of 50% (MIC50) and 90% (MIC90) of the organisms examined were also determined. All of the more recently synthesised 4-quinolones showed considerably greater activity than the parent compounds, nalidixic acid, pipemidic acid and cinoxacin, against the range of organisms used in this study. Ciprofloxacin and ofloxacin were the two most active of the 4-quinolones examined.

4-Quinolones↗

The comparative activity of twelve 4-quinolone antimicrobials against gram-positive and gram-negative anaerobes.

The minimal inhibitory concentrations (MICs) of twelve 4-quinolone antimicrobials were determined for the Bacteroides fragilis group (50), Bacteroides melaninogenicus (20), Bacteroides bivius (10), Fusobacterium spp. (10), anaerobic Gram-positive cocci (50) and Clostridium spp. (20). MICs were determined using an agar dilution technique in Mueller-Hinton agar supplemented with 10% lysed horse blood. The inoculum used was approximately 10(4) colony-forming units, contained in 10 microliter of Mueller-Hinton broth, which was applied to the agar plates using a multipoint inoculator. Following inoculation, plates were incubated at 37 degrees C for 48 h in an anaerobic atmosphere. The MIC of each antimicrobial for each isolate examined was determined as the lowest concentration of the antimicrobial which completely inhibited growth of the inoculum. The minimum concentrations required to inhibit the growth of 50% (MIC50) and 90% (MIC90) of the organism examined were also determined. All of the more recently synthesised 4-quinolones showed increased activity against the anaerobic bacteria used in this study. Ciprofloxacin and ofloxacin were the most active compounds examined (Bacteroides fragilis group MIC90 ciprofloxacin 4 micrograms/ml; ofloxacin 4 microgram/ml; Bacteroides melaninogenicus MIC90 ciprofloxacin 2 micrograms/ml, ofloxacin 2 micrograms/ml; Bacteroides bivius MIC90 ciprofloxacin 16 micrograms/ml, ofloxacin 32 micrograms/ml; Fusobacterium spp. MIC90 ciprofloxacin 2 micrograms/ml, ofloxacin 4 micrograms/ml; Clostridium spp. MIC90 ciprofloxacin 1 microgram/ml, ofloxacin 1 microgram/ml and anaerobic Gram-positive cocci MIC90 ciprofloxacin 4 micrograms/ml, ofloxacin 4 micrograms/ml).

Anaerobiosis↗

Protection against streptozotocin-induced diabetes by superoxide dismutase.

Suerpoxide dismutase was administered intravenously to rats 50 min prior to intravenous administration of a diabetogenic dose of streptozotocin. A dose of 45 mg/kg streptozotocin alone produced marked glucose intolerance and a decrease in pancreatic insulin content to less than 10% of control; both of these effects were abolished by prior administration of 105 mu/g of superoxide dismutase. Superoxide dismutase (105 mu/g) administered 50 min before 65 mg/kg intravenous streptozotocin did not prevent the development of diabetes. The fall in pancreatic insulin content seen with streptozotocin alone was, however, partially reversed by superoxide dismutase.

Animals↗