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P C Appelbaum

Publications and source records attributed to P C Appelbaum.

At least 127 records · Page 7Linked to original sources
PubMed1996

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.

Anti-Bacterial Agents↗
PubMed1996

Ability of RapID Yeast Plus System to identify 304 clinically significant yeasts within 5 hours.

The RapID Yeast Plus System (Innovative Diagnostic Systems, Norcross, Ga.) is a qualitative micromethod that uses conventional and chromogenic substrates for the identification of medically important yeasts. The ability of the RapID Yeast Plus system to accurately identify 304 clinical yeast isolates within 5 h was evaluated. The RapID Yeast Plus method correctly identified 286 (94.1%) of strains to the species level without the need for additional tests. A further 12 strains (3.9%) were classified as correct to the genus level or to a low-probability identification with two or more possibilities. In these latter cases, additional tests were required to delineate the correct identification. Organisms in the latter group comprised Candida parapsilosis (n = 1), Candida tropicalis (n = 1), Candida ciferrii (n = 1), Candida guilliermondii (n = 2), Candida humicola (n = 1), Candida kefyr (n = 1), Cryptococcus neoformans (n = 1), and Rhodotorula rubra (n = 4). Six strains (2.0%) were misidentified or did not yield codes in the manufacturer's database. These included one Candida utilis (identified as Candida famata/Candida guilliermondii), one Trichosporon beigelii (identified as Cryptococcus neoformans), one Candida diddensiae (identified as Candida albicans), one Candida membranaefaciens (identified as Candida parapsilosis), one Candida norvegensis (identified as Candida zeylanoides), and one Candida catenulata (no code) isolate; the last four strains are not included in the firm's current database. The RapID Yeast Plus system yielded excellent results and may be recommended for use in the routine laboratory for accurate same-day identification of clinically significant yeasts.

Candida↗
PubMed1996

Emerging resistance to antimicrobial agents in gram-positive bacteria. Pneumococci.

The prevalence of penicillin-resistant pneumococci is increasing worldwide. Methods for susceptibility testing, as well as in vitro susceptibility of penicillin-susceptible and -resistant strains to new and existing agents (including oral and parenteral streptogramins), are described. For all specimens except CSF, oxacillin screening followed by determination of penicillin minimum inhibitory concentrations (MICs) is satisfactory. For CSF, simultaneous testing of penicillin and cefotaxime or ceftriaxone by E-test is necessary. Of all available oral beta-lactams, amoxicillin yields the lowest MICs against penicillin-susceptible and -resistant pneumococci, and is the drug of choice for the treatment of otitis media. Cefotaxime and ceftriaxone yield MICs that are low enough to permit therapy of meningitic and nonmeningitic infections (the former in combination with vancomycin). The higher the strain's benzylpenicillin (penicillin G) MIC, the more likely it is that simultaneous resistance to nonrelated compounds such as tetracyclines, macrolides, and cotrimoxazole (trimethoprim/ sulfamethoxazole) will occur. None of the available quinolones should be used for therapy of pneumococcal infections. Of new and experimental drugs, some of the new quinolones, trovafloxacin, and oral and parenteral streptogramins are promising agents. Imipenem is epileptogenic, but meropenem has potential in the therapy of meningitis. Problematical infections caused by penicillin-resistant pneumococci include meningitis and otitis media. The optimal therapy of the latter two diseases has not yet been clearly delineated.

Administration, Oral↗
PubMed1995

Disseminated Mycobacterium marinum infection and bacteremia in a child with severe combined immunodeficiency.

We report an unusual case of disseminated dermatitis, osteomyelitis, and bacteremia in an immunocompromised host. An infant presented with a pustular skin rash resembling chicken pox, but culture of a skin lesion yielded Mycobacterium marinum. Upon further evaluation, severe combined immunodeficiency was diagnosed. Radiographs of the hands and feet showed evidence of osteomyelitis. M. marinum was isolated from blood and synovial fluid. We recommend a high level of suspicion for this organism in immunocompromised hosts who have been exposed to fresh water or salt water, particularly those of aquaria. Drug susceptibility testing of serial clinical isolates from our patient revealed development of high-level resistance to isoniazid and rifampin during therapy. We believe that treatment of disseminated M. marinum infections should include combinations of antimycobacterial agents chosen on the basis of results of susceptibility testing done by an experienced laboratory, thereby limiting the emergence of drug resistance.

Anti-Bacterial Agents↗
PubMed1995

Comparative activity of ampicillin, amoxycillin, amoxycillin/clavulanate and cefotaxime against 189 penicillin-susceptible and -resistant pneumococci.

Agar dilution and E-test MICs of penicillin G, ampicillin, amoxycillin, amoxycillin/clavulanate and cefotaxime were determined against 189 pneumococci. Addition of clavulanate did not influence amoxycillin MICs, MIC50/MIC90 (mg/L) for penicillin G, ampicillin, amoxycillin and cefotaxime were: Penicillin susceptible strains (62): 0.03/0.03; 0.03/0.06; 0.015/0.03; 0.015/0.06. Penicillin intermediate strains (69): 0.25/1.0; 0.25/4.0; 0.125/1.0; 0.125/1.0. Penicillin resistant strains (58): 2.0/4.0; 4.0/4.0; 1.0/2.0; 1.0/2.0. E-test MICs correlated well with those obtained by agar dilution.

Agar↗
PubMed1995

Activities of oral and parenteral agents against penicillin-susceptible and -resistant pneumococci.

This study examined bacteriostatic and bactericidal activities of oral and parenteral antibiotics for penicillin-susceptible and intermediately and fully penicillin-resistant pneumococci. beta-Lactamase inhibitors did not affect beta-lactam results. The activities of ampicillin, amoxicillin +/- clavulanate, WY-49605, cefuroxime, cefpodoxime, cefdinir, cefixime, and cefaclor against two penicillin-susceptible, two intermediately penicillin-resistant, and two fully penicillin-resistant pneumococcal strains were tested. For all three groups, bacteriostatic values of amoxicillin and WY-49605 were lower than were those of other beta-lactams tested. Of the cephalosporins, cefdinir, cefuroxime, and cefpodoxime yielded the lowest bacteriostatic values. All beta-lactams were bactericidal (reduced original counts by > or = 3 log10 CFU/ml) at 1 dilution above bacteriostatic values, except for cefpodoxime (bactericidal at 2 dilutions above bacteriostatic values for one susceptible strain and one intermediately resistant strain), cefuroxime (bactericidal at 2 dilutions above bacteriostatic values for one intermediately resistant strain), and ampicillin (bactericidal at 2 dilutions above bacteriostatic values for one intermediately resistant strain). The activities of piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, ceftriaxone, ceftazidime, and ciprofloxacin against four penicillin-susceptible, two intermediately penicillin-resistant, and four fully penicillin-resistant pneumococcal strains were evaluated. Bacteriostatic values of piperacillin, ampicillin, and ceftriaxone for all groups were lower than were those of ticarcillin and ceftazidime. Bacteriostatic values of ciprofloxacin were unaffected by penicillin susceptibility. All beta-lactams were bactericidal at 1 dilution above the bacteriostatic value, except for piperacillin (bactericidal at 2 dilutions above the bacteriostatic value for one intermediately resistant strain), ticarcillin (bactericidal at 2 dilutions above the bacteriostatic value for one susceptible strain and one resistant strain), ampicillin (bactericidal at 2 dilutions above the bacteriostatic value for two resistant strains), ceftriaxone (bactericidal at 2 dilutions above the bacteriostatic value for one resistant strain), and ceftazidime (bactericidal at 2 dilutions above the bacteriostatic value for one susceptible strain).

Administration, Oral↗
PubMed1995

Susceptibilities of 201 anaerobes to erythromycin, azithromycin, clarithromycin, and roxithromycin by oxyrase agar dilution and E test methodologies.

The susceptibility of 201 anaerobes to erythromycin, azithromycin, clarithromycin, and roxithromycin was tested by agar dilution and E test methods by using a commercially available plate and dish system (OxyDish) to provide anaerobic conditions. Plates were incubated for 48 h. MICs for 50% of strains tested and MICs for 90% of strains tested by agar dilution and E test methods corresponded within 1 doubling dilution for all compounds. When all antibiotics were considered together, agar and E test MICs were within 1 and 2 doubling dilutions of each other in 84 to 91% and > 99% of cases, respectively.

Agar↗
PubMed1995

Quinolone activity against anaerobes: microbiological aspects.

Currently available quinolones are either inactive or marginally active against anaerobic bacteria. This review summarises the in vitro activity of currently available as well as experimental quinolones against clinically significant anaerobic bacteria. Quinolones with low activity against anaerobes include ciprofloxacin, ofloxacin, levofloxacin, fleroxacin, pefloxacin, enoxacin, lomefloxacin and probably E 4868 and NM 441. Compounds with intermediate anaerobe activity include sparfloxacin, grepafloxacin, PD 131628 and AM 1155. Quinolones that are very active against anaerobes include clinafloxacin and DU 6859a. CP 99,219, a naphthyridone, is also very active against anaerobes. Toxicity problems have necessitated the withdrawal of some quinolones shown to have intermediate activity (temafloxacin and tosufloxacin) and the discontinuation of the development of some investigational agents (Win 57273 and BAY Y 3118) with high activity. Conclusions regarding the therapeutic value of quinolones against human anaerobic infections await further clinical toxicological and pharmacokinetic studies.

4-Quinolones↗
PubMed1994

Comparison of the E-test and conventional agar dilution methods for susceptibility testing of gram-negative anaerobic rods.

The E test was used to determine the susceptibility of 209 anaerobic Gram-negative rods to ampicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, piperacillin, piperacillin-tazobactam, clindamycin, chloramphenicol, and cefoxitin. Minimum inhibitory (MICs) were read where growth intersected the strips or where the upper indentation intersected the strips for beta-lactamase inhibitor-containing strips. Reference MICs were performed by the National Committee for Clinical Laboratory Standards agar dilution method. Organisms tested consisted of 117 Bacteroides fragilis group, 24 fusobacteria, and 68 other species (mainly Prevotella species). Agreement of MICs by both methods occurred in 33.4% of cases; 80.8% were within one, 99.0% were within two, and 99.95% were within three doubling dilutions apart. E-test results, expressed as MIC50/MIC90 values (microgram/ml), were as follows: ampicillin: 16/> 256; amoxicillin-clavulanate (2:1), 0.5/4; ticarcillin, 16/> 256; tircarcillin-clavulanate (2 micrograms/ml), 0.5/4; piperacillin, 16/> 256; piperacillin-tazobactam (4 micrograms/ml), 1/8; piperacillin-tazobactam (8:1), 2/8; cefoxitin, 8/64; clindamycin, 0.25/4; and chloramphenicol, 2/8. Conventional MIC methodology yielded MIC50s and MIC90s either identical to, or within one doubling dilution of, E-test results. Percentages of strains susceptible varied by < 3% between the two methods, except for cefoxitin (E test 5.2% lower). Based on these results, the E test is an accurate and practical method for use with the agents and organisms evaluated.

Agar↗
PubMed1994

Characterization of a beta-lactamase from Clostridium clostridioforme.

A beta-lactamase-producing strain of Clostridium clostridioforme isolated from human peritoneal fluid was examined by MIC testing and enzyme characterization. MICs of penicillins (64-512 mg/L) were higher than those of cephalosporins (8-128 mg/L); the strain was susceptible to cefoxitin (8 mg/L) and imipenem (1 mg/L). No enhancement of cephalosporin activity occurred when clavulanate was also added, but a limited degree of enhancement of penicillin activity (resulting in beta-lactam MICs higher than available NCCLS breakpoints) occurred when clavulanate, sulbactam or tazobactam was added simultaneously. By contrast, addition of BRL 42715 with amoxycillin, ticarcillin or piperacillin led to a drop in beta-lactam MICs from 512 to < or = 1 mg/L, with a drop from 64 to 1 mg/L when BRL 42715 was added with cefotaxime. All inhibitors were added at fixed concentrations of 2 mg/L. As determined spectrophotometrically, the enzyme hydrolysed penicillin G, cloxacillin and piperacillin (Vmax values (%) 372, 1816, 1001, respectively relative to cephaloridine) more efficiently than cephalosporins (69-191, with cephaloridine as 100%). Km values (microM) varied between 30-308 microM (penicillins) and 2-20 microM (cephalosporins). Relative enzyme efficiency (relative Vmax/Km with cephaloridine as 100) varied from 21-100 (cephalosporins) and 8-77 (penicillins). IC50 values (microM) with nitrocefin, piperacillin and penicillin G substrates (concentrations 20, 100 and 20 microM, respectively) were > 1000, 7, 3.5 (clavulanate); > 1000, 300, 59 (sulbactam), > 1000, 29, 7.7 (tazobactam); 0.0004, 0.001, 0.0018 (BRL 42715). The enzyme was not inhibited by EDTA, cefoxitin, cloxacillin or aztreonam, but was inhibited by pCMB.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1994

Susceptibilities of 123 strains of Xanthomonas maltophilia to eight beta-lactams (including beta-lactam-beta-lactamase inhibitor combinations) and ciprofloxacin tested by five methods.

This study evaluated the susceptibility of 123 Xanthomonas maltophilia strains to ticarcillin, ticarcillin-clavulanate, ampicillin, amoxicillin-clavulanate, ampicillin-sulbactam, piperacillin, piperacillin-tazobactam, imipenem, and ciprofloxacin by Kirby-Bauer disk, E test, and Sensititre dehydrated microdilution MIC and conventional agar dilution MIC methodology. Intermediate susceptibility breakpoints for members of the family Enterobacteriaceae were used. When results were analyzed as MICs for 50 and 90% of the strains tested and percentages of strains susceptible at the breakpoint, good correlation between the methods was observed, with ticarcillin-clavulanate clearly the most active beta-lactam by all four methods. However, when the various methods were compared with the agar dilution methodology by regression analysis, poor r2 values (0.3 to 0.7) were obtained for compounds with sufficient on-scale values to permit analysis. When the number of strains with log2 ratios of reference agar dilution MICs to test MICs of +3 to -3 were analyzed, correlation was also poor, with many major and very major discrepancies for all methods tested. Results obtained with time-kill studies of nine strains with discrepant ticarcillin-clavulanate MICs appeared to correlate best when compared at 24 h with agar dilution MICs. The concentration of ticarcillin-clavulanate required to reduce the colony count by > or = 2 log10 reduction values for eight of nine strains compared with that for growth controls was < or = 16.0/2.0 micrograms/ml at 6 h and ranged from 16.0/2.0 micrograms/ml to 128.0/2.0 micrograms/ml at 24 h. The susceptibility method of choice for X. maltophilia has not yet been standardized, but time-kill studies correlated best with agar dilution MICs.

Anti-Bacterial Agents↗
PubMed1994

Activity of CP 99,219 compared with those of ciprofloxacin, grepafloxacin, metronidazole, cefoxitin, piperacillin, and piperacillin-tazobactam against 489 anaerobes.

Agar dilution was used to compare the in vitro activity of CP 99,219 with those of ciprofloxacin, grepafloxacin, metronidazole, cefoxitin, piperacillin, and piperacillin-tazobactam against 489 anaerobes. CP 99,219 yielded a MIC for 50% of the strains tested (MIC50) of 0.25 micrograms/ml and a MIC90 of 1.0 microgram/ml, with 99.6% of the strains susceptible at a breakpoint of 2.0 micrograms/ml. Ciprofloxacin and grepafloxacin were less active (MIC50, 4.0 micrograms/ml; MIC90, 32.0 micrograms/ml and 2.0 and 16.0 micrograms/ml, respectively). Metronidazole was active against all gram-negative rods (MIC90, 4.0 micrograms/ml), but 31% of the gram-positive anaerobes were resistant at > 8.0 micrograms/ml. Cefoxitin was active against 84% of all strains at < or = 16.0 micrograms/ml, with a MIC50 of 4.0 micrograms/ml and a MIC90 of 32.0 micrograms/ml. Tazobactam enhanced the activity of piperacillin against > 95% of the beta-lactamase-producing gram-negative anaerobic rods (MIC90, 16.0 micrograms/ml).

Anti-Infective Agents↗
PubMed1994

Activity of WY-49605 compared with those of amoxicillin, amoxicillin-clavulanate, imipenem, ciprofloxacin, cefaclor, cefpodoxime, cefuroxime, clindamycin, and metronidazole against 384 anaerobic bacteria.

The National Committee for Clinical Laboratory Standards agar dilution method was used to compare the in vitro activity of WY-49605 (also called SUN/SY 5555 and ALP-201), a new broad-spectrum oral penem, to those of amoxicillin, amoxicillin-clavulanate, imipenem, ciprofloxacin, cefaclor, cefpodoxime, cefuroxime, clindamycin, and metronidazole against 384 clinically isolated anaerobes. These anaerobic organisms included 90 strains from the Bacteroides fragilis group, 87 Prevotella and Porphyromonas strains, non-B. fragilis group Bacteroides strains, 56 fusobacteria, 55 peptostreptococci, 49 gram-positive non-spore-forming rods, and 47 clostridia. Overall, WY-49605 had an MIC range of 0.015 to 8.0 micrograms/ml, an MIC at which 50% of the isolates are inhibited (MIC50) of 0.25 microgram/ml, and an MIC at which 90% of the isolates are inhibited (MIC90) of 2.0 micrograms/ml. Good activity against all anaerobe groups was observed, except for Clostridium difficile and lactobacilli (MIC50s of 4.0 and 2.0 micrograms/ml, respectively, and MIC90s of 8.0 and 2.0 micrograms/ml, respectively). Imipenem had an MIC50 of 0.03 microgram/ml and an MIC90 of 0.25 microgram/ml. Ciprofloxacin was much less active (MIC50 of 2.0 micrograms/ml and MIC90 of 16.0 micrograms/ml). By comparison, all oral beta-lactams were less active than WY-49605, with susceptibilities as follows: amoxicillin MIC50 of 8.0 micrograms/ml and MIC90 of > 256.0 micrograms/ml), amoxicillin-clavulanate MIC50 of 1.0 microgram/ml and MIC90 of 8.0 micrograms/ml, cefaclor MIC50 of 8.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml, cefpodoxime MIC50 of 4.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml, and cefuroxime MIC50 of 4.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml. Clindamycin was active against all groups except some members of the B. fragilis group, Fusobacterium varium, and some clostridia ( overall MIC50 of 0.5 micrograms/ml and overall MIC90 of 8.0 micrograms/ml). Metronidazole was active (MIC of less than or equal to 4.0 micrograms/ml) against all gram-negative anaerobic rods, but most gram-positive non-spore-forming rods, some peptostreptococci, and some clostridia were less susceptible. To date, WY-49605 is the most active oral beta-lactam against anaerobes: these results suggest clinical evaluation for clinical indications suitable for oral therapy.

Anti-Bacterial Agents↗
PubMed1994

In vitro susceptibilities of 185 penicillin-susceptible and -resistant pneumococci to WY-49605 (SUN/SY 5555), a new oral penem, compared with those to penicillin G, amoxicillin, amoxicillin-clavulanate, cefixime, cefaclor, cefpodoxime, cefuroxime, and cefdinir.

In vitro susceptibility of 185 penicillin-susceptible and -resistant pneumococci to WY-49605, a new oral penem, was compared with susceptibility to penicillin G, amoxicillin with and without clavulanate, cefixime, cefaclor, cefpodoxime, cefuroxime, and cefdinir. WY-49605 yielded MICs for 50 and 90% of the strains tested (MIC50 and MIC90, respectively) of 0.03 and 0.06, 0.125 and 0.5, and 0.5 and 1.0 micrograms/ml, respectively, against penicillin-susceptible, intermediately resistant, and fully resistant strains, respectively. The MIC50 and MIC90 for both amoxicillin and amoxicillin-clavulanate were identical and approximately 1 doubling dilution higher than those for WY-49605 and were < or = 0.06 and 0.125, 0.25 and 1.0, and 1.0 and 1.0 micrograms/ml, respectively. Cephalosporin MIC90s were all significantly higher than those of the latter three compounds for intermediately resistant and fully resistant strains.

Amoxicillin↗