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PubMed1978

Comparative beta-lactamase resistance and antistaphylococcal activities of parenterally and orally administered cephalosporins.

Two parenterally administered cephalosporins (cephalothin and cephapirin) and four orally administered cephalosporins (cephalexin, cephradine, cefatrizine, and cefaclor) were investigated by use of 29 beta-lactamase-producing strains of Staphylococcus aureus for determination of their relative rates of hydrolysis (RH) by beta-lactamase (RH of penicillin G =100) and their antistaphylococcal activities. Cephalothin (RH less than 0.01) and cephapirin (RH = 0.1) were relatively stable in the presence of staphylococcal beta-lactamase. Cephalexin and cephradine (RH of each = 0.3) were less stable than cephalothin and cephapirin but more stable than cefatrizine (RH = 1.4) and cefaclor (RH = 3.4). Agents that were more resistant to hydrolysis were affected less by the size of the inoculum when tested against large ;(10(7)) and small (10(3)) inocula of beta-lactamase-producing staphylococci than those that were hydrolyzed rapidly. Cephalothin and cephapirin were four to eight times more active than the orally administered cephalosporins against 10(3) staphylococci. Cephalosporins that are relatively stable in the presence of staphylococcal bata-lactamase may be preferable to less stable ones for treatment of serious infections due to beta-lactamase-producing staphylococci.

Administration, Oral↗
PubMed1988

In-vitro activity and beta-lactamase stability of LY163892.

LY163892 is a new orally absorbed carbacephem. It inhibited Streptococcus pyogenes and Str. pneumoniae at less than or equal to 1 mg/l, but was less active against group B streptococci and groups C, F, G and bovis streptococci with MICs of 1 to 2 mg/l for most but as high as 8 mg/l for some isolates. MIC90 of methicillin-susceptible Staphylococcus aureus was 8 mg/l, but greater than 128 mg/l for methicillin-resistant staphylococci. LY163892 had activity similar to cefaclor and cephalexin with MIC90 values of 16 mg/l for Escherichia coli, 8 mg/l for Klebsiella pneumoniae, Proteus mirabilis, Yersinia enterocolitica, but was more active against Haemophilus influenzae, and Branhamella catarrhalis. It had no activity against Enterobacter, Providencia, Serratia, and Pseudomonas and Bacteroides spp. LY163892 was more rapidly lytic than cephalexin. It was hydrolyzed by a number of plasmid and chromosomal beta-lactamases. For TEM-1, the Km = 354.7 microM, Vmax = 2.5 microMoles/min/mg of protein, P99 Km = 24.3 microM, Vmax = 28.9 microM/min/micrograms of protein, Staph. aureus PC Km = 47.4 microM, Vmax = 2.7 microMoles/min/mg of protein. Overall it had beta-lactamase stability similar to cefaclor, less than cephalexin, and markedly less than cefuroxime.

Amoxicillin↗
PubMed1990

In-vitro activity of azithromycin compared with other macrolides and oral antibiotics against Salmonella typhi.

The in-vitro activity of azithromycin against 60 clinical isolates of Salmonella typhi was determined by broth microdilution and compared with eight macrolides, including erythromycin, and with other orally administered antimicrobial agents (ampicillin, amoxycillin, cefaclor, trimethoprim/sulphamethoxazole, chloramphenicol, tetracycline, and ciprofloxacin). Azithromycin was more potent (MIC range 4-16 mg/l; MIC90 8 mg/l) than erythromycin (MIC range 32- greater than 128 mg/l; MIC90 greater than 128 mg/l). Of the other macrolides, only rosaramicin showed increased activity against Salm. typhi (MIC range 16-32 mg/l; MIC90 32mg/l) when compared with erythromycin. All 60 Salm. typhi were susceptible to ciprofloxacin (MIC greater than 0.5 mg/l). In 22 isolates, resistance to one or more of the following compounds occurred: ampicillin, amoxycillin, cefaclor, tetracycline, chloramphenicol, trimethoprim/sulphamethoxazole.

Anti-Bacterial Agents↗
PubMed1991

In-vitro activity of cefprozil (BMY 28100) and loracarbef (LY 163892) against pathogens obtained from middle ear fluid.

We compared the in-vitro activities of cefprozil, a novel oral cephalosporin, and of loracarbef, a new oral carbacephem, with other agents against middle ear fluid isolates obtained from children with acute otitis media. These included Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis. Cefprozil activity (MIC50 and MIC90) against S. pneumoniae was 0.25 and 0.50 mg/l; against H. influenzae 8 and 16 mg/l; against B. catarrhalis 2 and 2 mg/l. Loracarbef activity (MIC50 and MIC90) against S. pneumoniae was 1 and 2 mg/l; against H. influenzae 8 and 16 mg/l; against B. catarrhalis 1 and 8 mg/l. Cefprozil was four-fold more active against S. pneumoniae than loracarbef but similar to amoxycillin, amoxycillin/clavulanate, cefaclor, cefixime, cefuroxime and trimethoprim/sulfamethoxazole (TMP/SMX). Against H. influenzae, cefprozil was similar to loracarbef and other agents through less active than TMP/SMX and cefixime. Against B. catarrhalis, cefprozil was four-fold more active than loracarbef, cefaclor and cefixime but similar to the comparative antibiotics. Cefprozil and loracarbef activities were unaffected at pH 6 and 8 or in the presence of human serum, but there was a major diminution of activity for both agents at pH 5 and at inoculum sizes greater than or equal to 10(7) cfu/ml. Cefoprozil and loracarbef have consistent activity against middle ear pathogens and further pharmacokinetic and clinical studies appear warranted.

Acute Disease↗
PubMed1993

Susceptibility of 170 penicillin-susceptible and penicillin-resistant pneumococci to six oral cephalosporins, four quinolones, desacetylcefotaxime, Ro 23-9424 and RP 67829.

MICs of six oral cephalosporins (cefdinir, cefpodoxime, cefaclor, cefuroxime, cefixime and Ro 40-6890), four quinolones (ciprofloxacin, ofloxacin, OPC-17116 and fleroxacin), desacetylcefotaxime, Ro 23-9424 (a fused combination of fleroxacin + desacetylcefotaxime) and RP 67829 (a benzonaphthyridine) were determined for 49 penicillin-susceptible (S), 38 penicillin-intermediate (I), and 83 penicillin-resistant (R) strains of Streptococcus pneumoniae. All MICs were determined by a standardized agar dilution method utilizing Mueller-Hinton agar supplemented with sheep blood. MIC90s of OPC-17116 and RP 67829 were < or = mg/L, and were unaffected by penicillin-susceptibility. MICs of all beta-lactams increased with increasing penicillin-MICs, with cefdinir, cefpodoxime, cefuroxime and Ro 40-6890 being the most active compounds, followed by cefaclor and cefixime. MIC90s of ciprofloxacin and ofloxacin were 2 mg/L. MIC90s of Ro 23-9424 were lower than those of either parent compound (fleroxacin 8 mg/mL for all three groups; desacetylcefotaxime 0.5 mg/mL [S], 0.5 mg/mL [I], 4 mg/mL [R]; Ro 23-9424 0.125 mg/L [S], 0.25 mg/L [I], 0.5 mg/L [R]). The results indicated that several newly introduced and experimental antimicrobials have potential for the treatment of infections caused by resistant strains of S. pneumoniae.

Anti-Infective Agents↗
PubMed1994

Susceptibility of Moraxella catarrhalis isolates to beta-lactam antibiotics in relation to beta-lactamase pattern.

Moraxella catarrhalis isolates (n = 413) were collected from 20 clinical laboratories in England and Scotland in 1991 and were examined for beta-lactamase production by isoelectric focusing. beta-Lactamases were found in 375 isolates of which, 349 (93.1%) had BRO-1 enzyme and 26 (6.9%) had BRO-2. Minor variation in electrofocusing pattern occurred within both enzyme types. Ampicillin MICs for BRO-1 producers were 25-fold higher than for non-producers, but those for BRO-2 producers were raised only four-fold. MICs of cefaclor, cefixime, loracarbef, co-amoxiclav and cefetamet generally were two- to four-fold higher for BRO-1 producers than for BRO-2 producers and enzyme non-producers. Similarly, the inhibition zones of discs containing cefaclor, cefixime, loracarbef or co-amoxiclav were smaller for BRO-1 producers than for non-producers. Amongst the compounds tested, cefetamet seemed the least affected by beta-lactamase production in both MIC and disc tests. Overall, these results indicate that BRO-1 enzyme predominates amongst M. catarrhalis isolates from the UK, as in other countries, and suggest that BRO-1 production gives slight protection against many of the newer oral beta-lactams as well as causing ampicillin resistance.

Anti-Bacterial Agents↗
PubMed1995

Distribution of Streptococcus pneumoniae resistant to penicillin in the USA and in-vitro susceptibility to selected oral antibiotics.

Surveillance by 33 laboratories in 19 states during a 4 1/2 month period between December 1993 and April 1994 found that 263 of 1627 (16.2%) isolates of Streptococcus pneumoniae were resistant to penicillin. One hundred and seventy (10.4%) isolates were determined to be intermediately resistant to penicillin (MICs 0.1-1.0 mg/L and 93 (5.7%) were found to be highly resistant to penicillin (MICs > 2.0 mg/L). MIC90s for intermediately penicillin resistant strains were: amoxycillin/clavulanate 2.0 mg/L, cefaclor 64 mg/L, cefixime 32 mg/L, cefprozil 8 mg/L and loracarbef 128 mg/L. MIC90s for highly penicillin resistant strains were: amoxycillin/clavulanate 4.0 mg/L, cefaclor > or = 128 mg/L cefixime 64 mg/L, cefprozil 32 mg/L and loracarbef > or = 128 mg/L.

Administration, Oral↗
PubMed1996

The incidence and epidemiology of beta-lactam resistance in Haemophilus influenzae.

Consecutive isolates of Haemophilus influenzae were collected by the Public Health Laboratory, Bath between 1 June 1992 and 31 May 1993. Of 379 apparently distinct isolates, 216 originated from the respiratory tract, 102 from eyes and 61 from other sites. The minimum inhibitory concentrations of amoxycillin, amoxycillin/clavulanate, cefaclor, cefuroxime, cefotaxime and cefpodoxime were determined for each isolate. Forty strains (10.6%) were beta-lactamase producers. MIC50 and MIC90 values and the range of MICs were determined for all isolates. The overall resistance rates were: amoxycillin (MIC > 1.0 mg/L), 22.7%; amoxycillin/clavulanate (MIC > 1.0 mg/L), 14.8%; cefuroxime (MIC > 1.0 mg/L), 18.5%, (MIC > 4.0 mg/L), 5.5%; cefaclor (MIC > 8 mg/L), 15.6%; cefpodoxime (MIC > 1.0 mg/L), 0.3%; cefotaxime (MIC > 1.0 mg/L), 0%. Twenty non-beta-lactamase producing but beta-lactam resistant strains (cefuroxime MIC > 4.0 mg/L) were matched with 20 susceptible strains on the basis of patient age, sex, and specimen type. The strains were characterised by outer-membrane protein (OMP), random amplified polymorphic DNA (RAPD) and ribotyping patterns. Eleven of the 20 resistant strains were indistinguishable by the methods used, suggesting spread of a single beta-lactam resistant, non-beta-lactamase producing clone. The distribution of resistant strains within the local community was plotted geographically.

Adolescent↗
PubMed1996

Antimicrobial resistance among lower respiratory tract isolates of Streptococcus pneumoniae: results of a 1992-93 western Europe and USA collaborative surveillance study. The Alexander Project Collaborative Group.

One thousand, eight hundred and fifty-six Streptococcus pneumoniae strains, collected in 1992 and 1993 from 15 centres in Western Europe and USA were tested for susceptibility to 16 antibiotics. The overall resistance to penicillin was 23% (range 6-54%), with the highest prevalences in Madrid, Barcelona, Toulouse and Cleveland. Seven centres reported low-level penicillin resistance only. Amoxycillin was more active than ceftriaxone against strains with intermediate resistance to penicillin, and at least four-fold more active than cefuroxime; cefaclor and cefixime had poor activity. Against penicillin-resistant strains, ceftriaxone was slightly more active than amoxycillin, cefuroxime exhibited borderline activity and cefixime and cefaclor were inactive. Ten strains fully susceptible to penicillin had MICs of ceftriaxone > or = 0.1 mg/L; this may represent a first step towards the development of cephalosporin resistance. With the exception of fluoroquinolones, resistance to non-beta-lactam antibiotics (chloramphenicol, doxycycline, co-trimoxazole, erythromycin, clarithromycin and azithromycin) was considerably higher in penicillin-resistant strains compared with penicillin-susceptible isolates. Erythromycin-resistant isolates were also resistant to the other macrolides tested.

Anti-Bacterial Agents↗
PubMed1997

Time-kill studies on susceptibility of nine penicillin-susceptible and -resistant pneumococci to cefditoren compared with nine other beta-lactams.

Broth MIC and time-kill methodology was used to determine the activity of cefditoren relative to those of penicillin G, ampicillin, amoxycillin, WY-49605, cefuroxime, cefpodoxime, cefdinir, cefixime and cefaclor against three penicillin-susceptible, three intermediate and three penicillin-resistant pneumococci. MICs of all agents rose with those of penicillin G. Cefditoren was the most active agent (MICs 0.002-0.5 mg/L), followed by WY-49605 (0.008-1.0 mg/L), amoxycillin (0.015-2.0 mg/L), cefuroxime (0.015-4.0 mg/L), cefpodoxime (0.03-4.0 mg/L), ampicillin (0.015-8.0 mg/L), cefdinir (0.03-16.0 mg/L), cefixime (0.125-64.0 mg/L) and cefaclor (0.5-128.0 mg/L). All beta-lactams were bactericidal at the MIC after 24 h, and produced 90% killing after 12 h at concentrations above the MIC. Bactericidal concentrations of cefditoren, even for penicillin-resistant strains, were < or = 0.5 mg/L at 24 h. Additionally, cefditoren and WY-49605 were the only compounds that killed 99% of all strains after 6 h at > or = 4 x MIC. Cefditoren and amoxycillin killed 90% of all strains at 8 x MIC, and WY-49605 at 4 x MIC, after 4 h. Ampicillin had time-kill kinetics similar to those of amoxycillin, but MICs were 1-2 dilutions higher than the latter drug. Cefuroxime and cefpodoxime were the most active of other oral cephalosporins tested. Cefditoren and WY-49605 had the lowest MICs and most favourable time-kill kinetics of all beta-lactams tested.

Anti-Bacterial Agents↗
PubMed2005

Global distribution of TEM-1 and ROB-1 beta-lactamases in Haemophilus influenzae.

OBJECTIVES: To determine the global distribution of TEM-1 and ROB-1 beta-lactamases in Haemophilus influenzae isolated from patients with community-acquired respiratory tract infection during the first 4 years of the PROTEKT study (1999-2003). To investigate the activities of commonly used antibiotics against these isolates. METHODS: For 14 870 H. influenzae, MIC testing was performed using NCCLS broth microdilution methodology. For 2225 beta-lactamase-positive (BLP) H. influenzae, TEM-1 and ROB-1 genes were detected using a Taqman PCR method. RESULTS: beta-Lactamase positivity was 15.0% overall but varied greatly by country (<5% in several countries to 67.9% in Taiwan). Prevalences of TEM-1 and ROB-1 BLP H. influenzae were 93.7% and 4.6%, respectively, however almost all ROB-1 isolates were found in Canada, the USA and Mexico. ROB-1 isolates (n = 102) were less susceptible against cefaclor (29.4% versus 87.6%) and cefprozil (42.2% versus 91.9%) than TEM-1 (n = 2085) isolates. Differences in susceptibility rates for chloramphenicol, co-trimoxazole and tetracycline were also found between the two groups. CONCLUSIONS: The ROB-1 beta-lactamase was found almost exclusively in North America and was more active against cefaclor and cefprozil than the TEM-1 beta-lactamase.

Global Health↗
PubMed2005

Activation of vagal afferents in the rat duodenum by protein digests requires PepT1.

Intestinal infusion of protein digests activates a vago-vagal reflex inhibition of gastric motility. Protein digests release cholecystokinin (CCK) from enteroendocrine cells; however, the precise cellular mechanisms leading to vagal afferent activation is unclear. The hypothesis that the oligopeptide transporter PepT1 plays a major role in the initiation of this vago-vagal reflex was tested by recording activation of duodenal vagal afferent activity and inhibition of gastric motility in response to protein hydrolysates in the presence of 4-aminomethylbenzoic acid (4-AMBA), a competitive inhibitor of PepT1, or 4-aminophenylacetic acid (4-APAA), an inactive 4-AMBA analog. Duodenal infusion of the protein hydrolysate increased vagal afferent discharge and inhibited gastric motility; these responses were abolished by concomitant infusion of 4-AMBA, but not 4-APAA. Duodenal infusion with Cefaclor, a substrate of PepT1, increased duodenal vagal afferent activity; Cefaclor and protein hydrolysates selectively activated CCK-responsive vagal afferents. This study demonstrates that products of protein digestion increase spontaneous activity of CCK-sensitive duodenal vagal afferents via a mechanism involving the oligopeptide transporter PepT1.

4-Aminobenzoic Acid↗
PubMed1998

A multicenter study of the prevalence and susceptibility patterns of isolates of Streptococcus pneumoniae with reduced susceptibility to penicillin G in Louisiana.

Because of increasing reports of multiple-antibiotic-resistant strains of Streptococcus pneumoniae and associated clinical failures, this study was performed to determine the prevalence of multiresistance among strains from nine Louisiana medical centers. Using a National Committee for Laboratory Standards broth microdilution method, 481 strains were tested. Of these, 70% were penicillin-susceptible (PS), 23% had intermediate minimum inhibitory concentration values to penicillin (I), and 7% were fully resistant to penicillin (PR). The isolation rates (15% to 40% for I strains and 0% to 33% for PR strains) at the various medical centers varied appreciably. The prevalence of penicillin resistance was highest among upper respiratory isolates, while cross-resistance to other antimicrobials varied. The least cross-resistance was noted among PS strains. However, strains with reduced penicillin susceptibility had high levels of cross-resistance. Among I strains, the prevalence of cross-resistance (%) was noted for amoxicillin/clavulanate (6%), cefuroxime (71%), cefaclor (91%), ceftriaxone (13%), cefotaxime (34%), erythromycin (67%), azithromycin (32%), and clarithromycin (32%). For PR strains, the prevalence of cross-resistance was 97% for amoxicillin/clavulanate, cefuroxime, and cefaclor; 67% for ceftriaxone and erythromycin; 89% for cefotaxime; and 69% for azithromycin and clarithromycin. These data emphasize the high prevalence of multiple-antimicrobial-resistance among strains of S pneumoniae with reduced penicillin susceptibility in this geographic area.

Anti-Bacterial Agents↗
PubMed1993

Effect of pre-operative antibiotic treatment on the bacterial content of the tonsil.

The impact of 7 days pre-tonsillectomy antibiotics on the aerobic bacterial content of the tonsil was studied in 70 consecutive patients. One group received no antibiotic, one group received pre-operative amoxycillin and the final group, pre-operative cefaclor. The qualitative bacteriology was similar in the three groups Haemophilus influenzae was the predominant isolate present in the centre ('core') of the resected tonsil. Similar numbers of beta-lactamase producers including H. influenzae and Straphylococcus aureus were found in all three groups. Quantitative bacteriology of the tonsil core demonstrated that there was a significant reduction in core tonsil pathogens associated with antibiotic therapy. The most statistically significant difference was between the untreated control group and the cefaclor treated group. We conclude that in patients with established recurrent acute tonsillitis, oral antibiotics penetrate the diseased tonsil and influence the predominant core aerobic microflora.

Adolescent↗
PubMed1998

Clinical efficacy and tolerability of grepafloxacin in lower respiratory tract infection.

Studies in community-acquired pneumonia (CAP) have compared grepafloxacin, 600 mg o.d. for 7--10 days, with amoxycillin, 500 mg t.d.s., cefaclor, 500 mg t.d.s., or clarithromycin, 250 mg b.d. Grepafloxacin appeared to be clinically as effective as the comparators. In CAP caused by Haemophilus influenzae, grepafloxacin was significantly superior to amoxycillin (p=0.005) and cefaclor (p=0.003) and equivalent to clarithromycin in eradicating the infecting organism. Bacterial eradication with grepafloxacin in CAP caused by Moraxella catarrhalis or Streptococcus pneumoniae was effective and equivalent to the comparator antibiotic. In an open study, grepafloxacin was also effective in treating atypical pneumonia caused by Mycoplasma pneumoniae and Legionella pneumophila. In acute bacterial exacerbations of chronic bronchitis (ABECB), studies have found once-daily treatment with grepafloxacin, 400 mg or 600 mg for 7--10 days, to be equivalent to amoxycillin, 500 mg t.d.s., or ciprofloxacin, 500 mg b.d. In patients with documented infections, bacteriologic eradication with grepafloxacin, 400 mg or 600 mg o.d., was superior to amoxycillin, 500 mg t.d.s. Results from clinical trials so far indicate that grepafloxacin has a broad spectrum of activity covering all important community-acquired respiratory pathogens, and may be suitable for the empirical treatment of respiratory infection.

Journal Article↗
PubMed1978

Comparative in vitro activity of newer cephalosporins against anaerobic bacteria.

The in vitro susceptibilities of 408 recent clinical isolates of anaerobic bacteria against cefaclor, cephalexin, cephalothin, cefazolin, cefamandole, and cefoxitin were compared by an agar dilution technique. Against gram-positive bacteria, especially peptococci, peptostreptococci, and propionibacteria, cephalexin and cefaclor were significantly less active than cephalothin (P < 0.05). Cephalexin was also less active than cephalothin against clostridia and lactobacillus (P < 0.05). Against gram-negative bacteria, major differences were observed primarily with Bacteroides fragilis, against which cephalexin, cefazolin and cefoxitin were all significantly more active than cephalothin (P < 0.001). At concentrations of 16 mug per ml, however, all cephalosporins showed high in vitro activity, except against Lactobacillus species and B. fragilis. Cephalothin, cefazolin and cefamandole were considerably more active against the former, whereas cefoxitin was distinctly more active against the latter.

Anaerobiosis↗
PubMed1979

Comparative susceptibility of penicillinase-positive and -negative Neisseria gonorrhoeae to 30 antibiotics.

The minimal inhibitory concentrations of 30 antibiotics were determined by the agar dilution method for 17 penicillinase-positive and 50 penicillinase-negative strains of Neisseria gonorrhoeae. The latter included 42 strains that were penicillin susceptible (pen S) (minimal inhibitory concentration, <0.125 mug/ml) and 8 strains with intermediate resistance to penicillin (pen I; minimal inhibitory concentration, 0.125 to 0.5 mug/ml). Two penicillinase-resistant penicillins (methicillin and nafcillin) were inhibitory for penicillin-resistant (pen R) strains. Three new cephalosporins (cefuroxime, cefamandole, cefaclor) and a cephamycin (cefoxitin) were bacteriostatic (minimal inhibitory concentration </=0.8 mug/ml) for 90% of pen S, pen I, and pen R strains. Pen I strains were more resistant than pen R strains to 6 of 13 cephalosporins. Rifampin, erythromycin, spectinomycin, chloramphenicol, and the tetracyclines were inhibitory for both pen S and pen R strains. The minimal bactericidal concentrations of cefuroxime, cefamandole, cefaclor, and cefoxitin were measured for 17 pen R strains and eight pen I strains by serial dilution of the antibiotics in Trypticase soy broth supplemented with 1% Iso VitaleX and 1% hemoglobin. All tubes were subcultured after overnight incubation at 37 degrees C. Cefuroxime and cefoxitin were bactericidal at low concentrations (minimal bactericidal concentration, </=1.0 mug/ml) for 16 of 17 pen R strains and 6 of 8 pen I strains.

Anti-Bacterial Agents↗
PubMed1986

Comparative antibacterial activity of an arylglycyl oral cephalosporin, LY164846.

LY164846 is a semisynthetic arylglycyl cephalosporin which can be absorbed orally. It had in vitro activity comparable to that of cefaclor against beta-hemolytic streptococcal species and was two- to fourfold more active than cephalexin. Enterococci and Listeria species were resistant, and its activity against staphylococci was similar to that of other oral cephalosporins. Although some Bacteroides species were inhibited, the MICs for 25% were greater than or equal to 16 micrograms/ml. LY164846 was hydrolyzed by Staphylococcus aureus beta-lactamase and by cephalosporinases, but it was more stable than cefaclor.

Administration, Oral↗