In vitro activity of RU 64004, a new ketolide antibiotic, against gram-positive bacteria

The comparative in vitro activity of RU 64004 (also known as HMR 3004), a new ketolide antibiotic, was tested by agar dilution against approximately 500 gram-positive organisms, including multiply resistant enterococci, streptococci, and staphylococci. All streptococci were inhibited by < or = 1 microg of RU 64004 per ml. The ketolide was more potent than other macrolides against erythromycin A-susceptible staphylococci and was generally more potent than clindamycin against erythromycin A-resistant strains susceptible to this agent. Clindamycin-resistant staphylococci (MIC, > 128 microg/ml) proved resistant to the ketolide, but some erythromycin A- and clindamycin-resistant enterococci remained susceptible to RU 64004.     

Influence of erythromycin resistance, inoculum growth phase, and incubation time on assessment of the bactericidal activity of RP 59500 (quinupristin-dalfopristin) against vancomycin-resistant Enterococcus faecium

RP 59500, a mixture of two semisynthetic streptogramin antibiotics (quinupristin and dalfopristin), is one of a few investigational agents currently in clinical trials with inhibitory activity against multiple-drug-resistant strains of Enterococcus faecium. We evaluated the bactericidal activity of this antimicrobial against 30 recent clinical isolates of vancomycin-resistant E. faecium, including 23 erythromycin-resistant (MIC, >256 microg/ml) and 7 erythromycin-intermediate (MIC, 2 to 4 microg/ml) strains. All isolates were inhibited by RP 59500 at 0.25 to 1.0 microg/ml. The bactericidal activity of RP 59500 was markedly influenced by the erythromycin susceptibility of the strains and by several technical factors, such as inoculum growth phase and time of incubation of counting plates. As determined by time-kill methods, RP 59500 at a concentration of 2 or 8 microg/ml failed to kill erythromycin-resistant organisms under any conditions. Bactericidal activity was observed against all seven erythromycin-intermediate isolates when log-phase inocula were used and the cells were counted after 48 h of incubation (mean reductions in viable bacteria for RP 59500 at concentrations of 2 and 8 microg/ml, 3.45 and 3.50 log10 CFU/ml, respectively), but killing was diminished when the plates were examined at 72 h (mean killing, 3.06 and 2.95 log10, CFU/ml, respectively). No bactericidal activity was observed when stationary-phase cultures were used. On the basis of these data, we expect that bactericidal activity of RP 59500 against the multiple-drug-resistant E. faecium strains currently encountered would be distinctly uncommon.     

Comparative antimicrobial activity of RP 59,500 (quinupristin-dalfopristin), the first semisynthetic injectable streptgramin, against gram-positive cocci and other recent clinical pathogens

RP 59,500 (Quinupristin-Dalfopristin) is the first semisynthetic injectable streptogramin antimicrobial agent, which is a combination of quinupristin and dalfopristin in a 30:70 ratio. The components of RP 59,500 act synergically to provide bactericidal activity through action at different sites on bacterial ribosomes. In the present study, the antimicrobial activity of RP 59,500 was compared with those of four macrolides (erythromycin, clarithromycin, azithromycin, roxithromycin). Susceptibility testing was carried out by microdilution method on 303 strains of 10 species, especially antibiotic-resistant Gram-positive cocci. RP 59,500 was active against a wide range of Gram-positive cocci including methicillin-resistant Staphylococci and penicillin-resistant Streptococcus pneumoniae. The MICs90 of RP 59,500 against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis were both 0.25 microgram/ml, although those of four macrolides were higher than 32 micrograms/ml. The MICs90 of RP 59,500 against penicillin-sensitive, -intermediate and -resistant S. pneumoniae were all 0.5 microgram/ml, although those of four macrolides against penicillin-resistant S. pneumoniae were higher than 32 micrograms/ml. RP 59,500 also exhibited equivalent activities to the four macrolides against strains of Streptococcus pyogenes. Streptococcus agalactiae and Moraxella catarrhalis. RP 59,500 exhibited the highest activities against Enterococcus faecalis, Enterococcus faecium and Enterococcus avium strains which are intrinsically resistant to most antimicrobial agents. No cross-resistance was observed between RP 59,500 and the four macrolides, which will merit attention in future clinical trials of the agent. The effect of human serum on the MIC of RP 59,500 was studied with strains of S. aureus, S. epidermidis and E. faecalis. The presence of 20% (V/V) serum had little or no effect on the MIC, although 50% (V/V) serum increased MICs by 4-8 folds. Laboratory-induced resistance to RP 59,500 occurred in a stepwise fashion in broth cultures of S. aureus, S. epidermidis and E. facalis strains and the induction rate was slow and no more than four fold increases were observed. Population analysis was performed on RP 59,500 and the reference macrolides against S. aureus ATCC 25,923 strain. Although low frequencies (less than 0.01%) of resistant sub-population were detected with EM, CAM, AZM and RXM, no RP 59,500-resistant sub-population was detected in this study.     

Killing kinetics of RP 59500 and pristinamycin against penicillin-resistant pneumococci

The killing kinetics of two streptogramins, RP 59500 and pristinamycin against seventeen isolates of penicillin-susceptible and resistant pneumococci were studied. The antibiotics were tested at 1x, 2x and 4x the MIC for each individual isolate. The results showed a very good and rapid bactericidal activity within 1 hour for concentrations equal or greater to the MIC. These antibiotics are very promising agents for the treatment of infections due to multiresistant pneumococci.     

In vitro activities of two glycylcyclines against gram-positive bacteria

The glycylcyclines designated CL 329,998 and CL 331,002 are N,N-dimethylglycylamido derivatives of minocycline and 6-demethyl-6-deoxytetracycline, respectively. In vitro activities of these two antimicrobial agents were compared with those of tetracycline, minocycline, and seven other antimicrobial agents against 412 gram-positive organisms. Both new drugs were significantly more active than minocycline against methicillin-resistant Staphylococcus aureus (MICs for 90% of isolates tested, 0.25 and 0.5 microgram/ml versus 4 micrograms/ml). CL 329,998 inhibited all streptococci, lactobacilli, and Leuconostoc spp. at concentrations of < or = 0.5 microgram/ml, with CL 331,002 slightly less active against some species. All enterococci, including minocycline-resistant and multidrug-resistant isolates, were inhibited at < or = 0.5- and < or = 1.0-microgram/ml concentrations of the new drugs, respectively. Only bacteriostatic activity was evident by time-kill curves. The two glycylcyclines demonstrated activities in vitro that were superior to those of minocycline against several gram-positive bacterial species, and at relatively low concentrations, they inhibited isolates resistant to both tetracycline and minocycline.     

In vitro activity of a new ketolide antibiotic, HMR 3647, against Chlamydia pneumoniae

The in vitro activities of HMR 3647, roxithromycin, erythromycin, and azithromycin against 19 strains of Chlamydia pneumoniae were tested. The MIC at which 90% of the isolates are inhibited and the minimum bactericidal concentration at which 90% of the isolates are killed of HMR 3647 were 0.25 microgram/ml (range, 0.015 to 2 micrograms/ml). Nine recently obtained clinical isolates from children with pneumonia were more susceptible (MICs, 0.015 to 0.0625 microgram/ml) than older strains that had been passaged more extensively.     

In vitro activity of the new glycopeptide LY333328 against multiply resistant gram-positive clinical isolates

In order to assist the medical team in the decision-making process and in adequate counselling of patients when encountering technical difficulties at the time of embryo transfer, we investigated the effect of difficult embryo transfer, with or without the need for cervical dilatation or repeated sequential attempts because of retained embryos in the catheter system, on in-vitro fertilization (IVF) pregnancy rates and outcome. A total of 854 consecutive embryo transfer procedures were prospectively categorized as (i) easy (smooth, unforced), (ii) difficult (requiring uterine manipulation or increased force or cervical grasping and/or accompanied by trauma), (iii) requiring cervical dilatation, or (iv) multiple (two or three) sequential attempts because of embryos retained in the catheter system. Embryo transfer was easy in 734 cases (85.9%). It was difficult in 72 (8.4%), cervical dilatation was required in 21 (2.5%), and one or two repeated attempts were needed in 27 cases (3.2%). Pregnancy rates for the different categories of embryo transfer were 23.3, 23.6, 23.8 and 29.6% respectively. There were no significant differences in the percentage of the ongoing/delivered pregnancies for the different categories of embryo transfer (69, 64.6, 60 and 62.5% respectively). There were no significant differences in the distribution of embryo transfer types among the six infertility specialists who performed the procedures. To conclude, embryo transfers that are difficult to perform or that require cervical dilatation or repeated attempts do not adversely affect pregnancy rates and outcome following IVF. Cervical dilatation, if needed for patients with cervical stenosis, should be performed at the time of the embryo transfer and not earlier. Surgical transmyometrial embryo transfer or rescheduling patients for delayed embryo transfer could be avoided in most patients. This information is important for patient management and counselling in cases of embryo transfer that are not easy to perform.     

MIC and time-kill study of antipneumococcal activities of RPR 106972 (a new oral streptogramin), RP 59500 (quinupristin-dalfopristin), pyostacine (RP 7293), penicillin G, cefotaxime, erythromycin, and clarithromycin against 10 penicillin-susceptible and -resistant pneumococci

Broth MICs and time-kill studies were used to test the activity of RP 59500 (quinupristin-dalfopristin), RPR 106972, pyostacine (RP 7293), erythromycin, clarithromycin, and cefotaxime for four penicillin-susceptible (MICs of 0.008 to 0.03 microgram/ml), two penicillin-intermediate (MIC of 0.25 microgram/ml), and four penicillin-resistant (MIC of 2.0 to 4.0 micrograms/ml) strains of pneumococci: 6 of 10 strains were resistant to macrolides (MICs of > or = 0.5 microgram/ml). MICs of RP 59500 (0.5 to 1.0 microgram/ml), RPR 106972 (0.125 to 0.25 microgram/ml), and pyostacine (0.125 to 0.25 microgram/ml) did not alter with the strain's penicillin or macrolide susceptibility status. Three penicillin-susceptible strains and one penicillin-intermediate strain were susceptible to macrolides (MICs of < or = 0.25 microgram/ml); the macrolide MICs for the remaining strains were > or = 4.0 micrograms/ml. Cefotaxime MICs rose with those of penicillin G, but all strains were inhibited at MICs of < or = 2.0 micrograms/ml. RP 59500 was bactericidal for all strains after 24 h at 2 x MIC and yielded 90% killing of all strains at 6 h at 2 x MIC; at 8 x MIC, RP 59500 showed 90% killing of six strains within 10 min (approximately 0.2 h). In comparison, RPR 106972 was bactericidal for 9 of 10 strains at 2 x MIC after 24 h and yielded 90% killing of all strains at 2 x MIC after 6 h; 90% killing of six strains was found at 8 x MIC at 0.2 h. Results for pyostacine were similar to those of RPR 106972. Erythromycin and clarithromycin were bactericidal for three of four macrolide-susceptible strains after 24 h at 4 x MIC. Clarithromycin yielded 90% killing of three strains at 8 x MIC after 12 h. Cefotaxime was bactericidal for all strains after 24 h at 4 x MIC, yielding 90% killing of all strains after 6 h at 4 x MIC. All three streptogramins yielded rapid killing of penicillin- and erythromycin-susceptible and -resistant pneumococci and were the only compounds which killed significant numbers of strains at 0.2 h.     

Pharmacodynamics of RP 59500 (quinupristin-dalfopristin) administered by intermittent versus continuous infusion against Staphylococcus aureus-infected fibrin-platelet clots in an in vitro infection model

We evaluated the bactericidal activity of RP 59500 (quinupristin-dalfopristin) against fibrin-platelet clots (FPC) infected with two clinical isolates of Staphylococcus aureus, one constitutively erythromycin and methicillin resistant (S. aureus AW7) and one erythromycin and methicillin susceptible (S. aureus 1199), in an in vitro pharmacodynamic infection model. RP 59500 was administered by continuous infusion (peak steady-state concentration of 6 microg/ml) or intermittent infusion (simulated regimens of 7.5 mg/kg of body weight every 6 h (q6h) q8h, and q12h. FPCs were infected with S. aureus to achieve an initial bacterial density of 10(9) CFU/g. Model experiments were run in duplicate over 72 h. Two FPCs were removed from each model at 0, 12, 24, 36, 48, and 72 h, and the bacterial densities (in CFU per gram) were determined and compared to those of growth control experiments. Additional samples were also removed from the model over the 72-h period for pharmacokinetic evaluation. All regimens significantly (P < or = 0.01) decreased bacterial densities in the infected FPCs for both isolates compared to growth controls. This occurred even though MBCs were equal to or greater than the RP 59500 concentrations achieved in the models. There were no significant differences found between the dosing frequencies and levels of killing when examining each isolate separately. However, examination of the residual bacterial densities (CFU per gram at 72 h) and visual inspection of the overall killing effect (killing curve plots over 72 h) clearly demonstrated a more favorable bactericidal activity against 1199 than against the AW7 isolate. This was most apparent when the q8h and the q12h AW7 regimens were compared to all 1199 treatment regimens by measuring the 72-h bacterial densities (P < or = 0.01). Killing (99.9%) was not achieved against the AW7 isolate. However, a 99.9% kill was demonstrated for all dosing regimens against the 1199 isolate. The area under the concentration-time curve from 0 to 24 h was found to be significantly correlated with reduction in bacterial density for the AW7 isolate (r = 0.74, P = 0.04). No resistance was detected during any experiment for either isolate. RP 59500 efficacy against constitutively erythromycin- and methicillin-resistant S. aureus may be improved by increasing organism exposure to RP 59500 as a function of dosing frequency.     

Treatment of vancomycin-resistant Enterococcus faecium with RP 59500 (quinupristin-dalfopristin) administered by intermittent or continuous infusion, alone or in combination with doxycycline, in an in vitro pharmacodynamic infection model with simulated endocardial vegetations

Quinupristin-dalfopristin is a streptogramin antibiotic combination with activity against vancomycin-resistant Enterococcus faecium (VREF), but emergence of resistance has been recently reported. We studied the activity of quinupristin-dalfopristin against two clinical strains of VREF (12311 and 12366) in an in vitro pharmacodynamic model with simulated endocardial vegetations (SEVs) to determine the potential for resistance selection and possible strategies for prevention. Baseline MICs/minimal bactericidal concentrations (microg/ml) for quinupristin-dalfopristin, quinupristin, dalfopristin, and doxycycline were 0.25/2, 64/>512, 4/512, and 0.125/8 for VREF 12311 and 0.25/32, 128/>512, 2/128, and 0.25/16 for VREF 12366, respectively. Quinupristin-dalfopristin regimens had significantly less activity against VREF 12366 than VREF 12311. An 8-microg/ml simulated continuous infusion was the only bactericidal regimen with time to 99.9% killing = 90 hours. The combination of quinupristin-dalfopristin every 8 h with doxycycline resulted in more killing compared to either drug alone. Quinupristin-dalfopristin-resistant mutants (MICs, 4 microg/ml; resistance proportion, approximately 4 x 10(-4)) emerged during the quinupristin-dalfopristin monotherapies for both VREF strains. Resistance was unstable in VREF 12311 and stable in VREF 12366. The 8-microg/ml continuous infusion or addition of doxycycline to quinupristin-dalfopristin prevented the emergence of resistance for both strains over the 96-h test period. These findings replicated the development of resistance reported in humans and emphasized bacterial factors (drug susceptibility, high inoculum, organism growth phase) and infectious conditions (penetration barriers) which could increase chances for clinical resistance. The combination of quinupristin-dalfopristin with doxycycline and the administration of quinupristin-dalfopristin as a high-dose continuous infusion warrant further study to determine their potential clinical utility.     

Treatment of vancomycin-resistant Enterococcus faecium infections with an investigational streptogramin antibiotic (quinupristin/dalfopristin): a report of fifteen cases

OBJECTIVE: Previous studies of surgical treatment for acromegaly have used varied criteria for 'cure', but elevated GH levels are considered to be associated with continuing disease activity. We wished to analyse the results of transsphenoidal pituitary surgery for acromegaly and assess the longer-term outcome for patients not offered further treatment when post-operative levels of GH < 5 mU/l were achieved. DESIGN: We studied a retrospective group of patients who underwent transsphenoidal surgery for acromegaly at St Bartholomew's Hospital between 1985 and 1993. PATIENTS: One hundred consecutive patients (53 male, mean age 46 years, range 18-68 years) undergoing transsphenoidal surgery for acromegaly were assessed. The patients were followed for a mean of 3.8 years (range 0.5-8 years) after operation. MEASUREMENTS: GH levels are represented as a mean value from a four-point day curve taken at 0830, 1300, 1700 and 1900 h. ACTH reserve was assessed basally and, if this was normal, with the insulin tolerance or glucagon tests. TSH, T4, PRL, LH, FSH, testosterone or oestradiol and plasma and urine osmolality were also measured. RESULTS: Post-operatively, 42% of patients achieved a mean GH level of < 5 mU/l. The success of surgery was related to the preoperative GH level; 65% of the patients with preoperative GH levels < 20 mU/l but only 18% of the patients with GH levels > 100 mU/l achieved post-operative GH values < 5 mU/l. In addition, tumour size influenced the outcome of surgery with 61% of patients with a microadenoma but only 23% of patients with a macroadenoma achieving post-operative GH levels of < 5 mU/l. Of the 42 patients considered in remission post-operatively (mean GH < 5 mU/l), 32 were available for long-term follow-up and were not offered any further treatment: only one of these has shown evidence of mild biochemical recurrence after a mean follow-up of 3.8 years (range 0.5-8). There were no peri-operative deaths. Two patients required surgical repair for CSF leaks and there were eight documented cases of meningitis. Permanent diabetes insipidus was noted in eight patients post-operatively. New anterior pituitary deficiency occurred in 21% of patients following surgery; 73% had unaltered pituitary function and in 6% recovery of partial hypopituitarism was noted. CONCLUSIONS: The stated outcome of surgery depends on the criteria adopted. Safe GH levels (mean levels < 5 mU/l) can be achieved in 42% of an unselected series of patients with acromegaly and if the tumour is a microadenoma this figure rises to 61%. Based on the current evidence it is safe not to offer further treatment to those patients in whom post-operative GH < 5 mU/l are achieved.     

Activities of the semisynthetic glycopeptide LY191145 against vancomycin-resistant enterococci and other gram-positive bacteria

LY191145 is the prototype of a series of compounds with activities against vancomycin-resistant enterococci derived by modification of the glycopeptide antibiotic LY264826. LY191145 had MICs for vancomycin- and teicoplanin-resistant enterococci of < or = 4 micrograms/ml for 50% of isolates and < or = 16 micrograms/ml for 90% of isolates. Its MICs for vancomycin-resistant, teicoplanin-susceptible enterococci were 1 to 8 micrograms/ml. LY191145 retains the potent activities of its parent compound against staphylococci and streptococci. In vivo studies in a mouse infection model confirmed these activities. This compound indicates the potential of semisynthetic glycopeptides as agents against antibiotic-resistant gram-positive bacteria.     

In vitro activity of dirithromycin against Chlamydia trachomatis

Dirithromycin is a new macrolide antibiotic with an active metabolite, erythromycylamine. We evaluated the in vitro activities of both drugs against 16 isolates of Chlamydia trachomatis and compared them with that of doxycycline. In vitro susceptibility testing was performed with McCoy cell monolayers. The MIC was defined as the lowest concentration of antibiotic without inclusions. The MBC was defined as the lowest concentration of antibiotic yielding no inclusions after passage onto 24-h-old antibiotic-free McCoy cell monolayers. Dirithromycin and erythromycylamine appeared to be equally effective against these 16 strains of C. trachomatis (MIC for 90% of strains tested, 1 mg/ml; MBC for 90% of strains tested, 2 micrograms/ml). Both were less active than doxycycline (MIC for 90% of strains tested, 0.06 micrograms/ml; MBC for 90% of strains tested, 0.12 micrograms/ml). The combination of dirithromycin and erythromycylamine appeared to be additive.     

Antimicrobial activity of quinupristin-dalfopristin (RP 59500, Synercid) tested against over 28,000 recent clinical isolates from 200 medical centers in the United States and Canada

A total of 200 medical center laboratories in the USA and Canada contributed results of testing quinupristin-dalfopristin, a streptogramin combination (formerly RP 59500 or Synercid), against 28,029 Gram-positive cocci. Standardized tests [disk diffusion, broth microdilution, Etest (AB BIODISK, Solna, Sweden)] were utilized and validated by concurrent quality control tests. Remarkable agreement was obtained between test method results for characterizing the collection by the important emerging resistances: 1) oxacillin resistance among Staphylococcus aureus (41.0 to 43.7%); 2) vancomycin resistance among Enterococcus faecium (50.0 to 52.0%); and 3) the penicillin nonsusceptible rate for pneumococci (31.1% overall, with 10.6% at MICs of > or = 2 micrograms/mL). The quinupristin-dalfopristin MIC90 for oxacillin-susceptible and -resistant S. aureus was 0.5 microgram/mL and 1 microgram/mL, respectively. The quinupristin-dalfopristin MIC90 for vancomycin-resistant E. faecium was 1 microgram/mL, and only 0.2% of isolates were resistant. Other Enterococcus species were generally not susceptible to the streptogramin combination but were usually inhibited by ampicillin (86 to 97% susceptible; MIC50, 1.0 microgram/mL) or vancomycin (86 to 95%; MIC50, 1.0 microgram/mL). Among all tested enterococci, the rate of vancomycin resistance was 16.2%. The quinupristin-dalfopristin MIC90 (0.75 microgram/mL) for 4,626 tested Streptococcus pneumoniae strains was not influenced by the penicillin or macrolide susceptibility patterns. When five regions in the USA and Canada were analyzed for significant streptogramin and other antimicrobial spectrum differences, only the Farwest region had lower numbers of streptogramin-susceptible E. faecium. Canadian strains were generally more susceptible to all drugs except chloramphenicol and doxycycline when tested against E. faecalis (73% and 89% susceptible, respectively). The U.S. Southeast region had S. pneumoniae strains less susceptible to macrolides (73%) but had more susceptibility among E. faecium isolates tested against vancomycin and ampicillin. The Northeast region of the USA had the greatest rate of vancomycin resistance among enterococci. Strains retested by the monitor because of quinupristin-dalfopristin resistance (MICs, > or = 4 micrograms/mL) were generally not confirmed (2.2% validation), and only 0.2% of E. faecium isolates were identified as truly resistant. The most common errors were: 1) species misidentification (28.0%); 2) incorrect susceptibility results (65.6%); and 3) mixed cultures (4.3%) tested by participants. Overall, quinupristin-dalfopristin was consistently active (> or = 90% susceptible) against major Gram-positive pathogens in North America, regardless of resistance patterns to other drug classes and geographic location of their isolation.     

In vitro activity of macrolides against intracellular Legionella pneumophila

The antibacterial effects of clarithromycin, azithromycin, and erythromycin were determined against five strains of Legionella pneumophila including L. pneumophila ATCC 33823 and four clinical isolates. Extracellular minimum inhibitory concentrations (MICs) and MBCs were determined by a microdilution method. Clarithromycin was the most active drug (MIC < or = 0.015-0.06), followed by azithromycin (MIC 0.03-0.12) and erythromycin (MIC 0.06-0.25). The antibacterial effect of these macrolides was then determined against L. pneumophila grown intracellularly in MRC-5 human fetal lung fibroblast cells. At two and eight times the extracellular MBC, erythromycin, azithromycin, and clarithromycin were equally effective in inhibiting growth of these five strains of intracellular L. pneumophila.     

In vitro evaluation of activities of nitazoxanide and tizoxanide against anaerobes and aerobic organisms

The antibacterial activities of nitazoxanide and its main metabolite, tizoxanide, were tested against a broad range of bacteria, including anaerobes. Metronidazole, amoxicillin, amoxicillin-clavulanic acid, piperacillin, cefoxitin, imipenem, and clindamycin were used as positive controls. MICs were determined by reference agar dilution methods. The 241 anaerobes were all inhibited by nitazoxanide, with the MICs at which 90% of isolates are inhibited (MIC90S) being between 0.06 and 4 mg/liter with the exception of those for Propionibacterium species, for which the MIC90 was 16 mg/liter. The MIC90s of nitazoxanide were 0.5 mg/liter for the Bacteroides fragilis group (80 strains), 0.06 mg/liter for Clostridium difficile (21 strains), and 0.5 mg/liter for Clostridium perfringens (16 strains). Metronidazole showed a level of activity comparable to that of nitazoxanide except against Bifidobacterium species, against which it was poorly active, and Propionibacterium species, which were resistant to metronidazole. The other antibiotics showed various levels of activity against anaerobes, with imipenem along with nitazoxanide being the most active agents tested. Tizoxanide was less effective than nitazoxanide except against the B. fragilis group, against which its activity was similar to that of nitazoxanide. Under aerobic conditions, nitazoxanide demonstrated poor activity against members of the family Enterobacteriacae and Pseudomonas, Staphylococcus, and Enterococcus species. The same results were obtained when culture was performed under anaerobic conditions with the notable exception of the results against Staphylococcus aureus. The MICs of nitazoxanide were in the range of 2 to 4 mg/liter for 34 clinical isolates of S. aureus, 12 of which were methicillin resistant, while tizoxanide was not effective.     

In vitro activity of biapenem against beta-lactamase producing Enterobacteriaceae

The activity of biapenem was compared with that of imipenem and cefotaxime against 108 strains of beta-lactamase producing Enterobacteriaceae. Biapenem and imipenem were very active, inhibiting 90% of the strains at a concentration of 0.5 microgram/ml. Both carbapenems were very active against plasmidic beta-lactamase producers, with MIC90s below 1 microgram/ml. However, the MIC90 of biapenem for cephalosporinase producers was 1 microgram/ml. Against strains producing extended-spectrum beta-lactamases, biapenem exhibited better activity against TEM-type producers (MIC90 0.25 microgram/ml) than against SHV-type producers (MIC90 0.5 microgram/ml). Overall, the in vitro antibacterial activity of biapenem is similar to that of imipenem.     

In vitro activities of the ketolide HMR 3647 against recent gram-positive clinical isolates and Haemophilus influenzae

The ketolide HMR 3647 (previously RU 66647) was evaluated against 2, 563 recent clinical isolates of gram-positive pathogens and 200 Haemophilus influenzae isolates. HMR 3647 was active against macrolide-resistant streptococci, including pneumococci, but was not active against macrolide- or lincosamide-resistant staphylococci. Against H. influenzae, the potency of HMR 3647 was similar to that of azithromycin.     

In vitro antibiotic susceptibility of salmonellae

In vitro antibiotic susceptibilities were determined for 101 strains of salmonellae. Resistance to chloramphenicol and ampicillin was low. Cefamandole was active against the majority of strains and deserves further evaluation.