Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Penicillin Resistance”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1997

In vivo efficacy of cefotaxime and amoxicillin against penicillin-susceptible, penicillin-resistant and penicillin---cephalosporin-resistant strains of Streptococcus pneumoniae in a mouse pneumonia model.

OBJECTIVE: To compare cefotaxime (CTX) to amoxicillin (AMO) (usually considered the definitive therapy for penicillin-susceptible Streptococcus pneumoniae infections) in an immunocompromised mouse pneumonia model. METHODS: Three S. pneumoniae clinical isolates were used: two serotype 19 strains, a penicillin-susceptible (Ps) strain (penicillin MIC=0.03 microg/mL) and a highly penicillin-resistant (Pr) strain (penicillin MIC=4 microg/mL), and one serotype 23F strain, a penicillin---cephalosporin-resistant (CFTR) strain (CTX MIC=4 microg/mL). RESULTS: CTX activity in this mouse model of pneumonia induced by the highly penicillin-resistant strain of S. pneumoniae was lower than expected from its low MIC against this organism. Furthermore, AMO had greater efficacy than CTX against a CFTR S. pneumoniae strain. CONCLUSION: Our data suggest that there is no major difference in the in vivo efficacy of the two agents, cefotaxime and amoxicillin, against penicillin-resistant and penicillin---cephalosporin-resistant S. pneumoniae.

Journal Article↗
PubMed1999

The epidemiology of penicillin resistance in Streptococcus pneumoniae.

Pneumococci are not intrinsically resistant penicillin or other commonly used antibiotics. Penicillin-resistant strains were not encountered until 1965 when two strains were identified in Boston. At that time, the resistance was of a minor degree and its significance was not recognized by the authors. In 1971, resistant strains were encountered in New Guinea and, by the late 1970s, penicillin-resistant pneumococci had spread worldwide. By the early 1980s, areas where more than 10% of isolates were found to be penicillin resistant included Israel, Poland, Spain, South Africa, New Guinea, and the United States from New Mexico to Alaska. In this decade a number of countries including South Korea, Hungary, and Spain have reported dramatic increases in penicillin resistance. Penicillin resistance, once acquired by a virulent pneumococcal clone, has the ability to spread from country to country and to other continents in a relatively short time. Coincident with the increasing penicillin resistance has been the development of resistance to a wide variety of other antibiotics, including other cephalosporins, macrolides, trimethoprim-sulfamethoxazole, tetracycline, and chloramphenicol. Some strains are so highly resistant as to significantly impair our ability to treat patients with meningitis and to choose an appropriate oral agent for the treatment of pneumococcal otitis media.

Canada↗
PubMed2004

Daptomycin is highly efficacious against penicillin-resistant and penicillin- and quinolone-resistant pneumococci in experimental meningitis.

The penetration of daptomycin, a new lipopeptide antibiotic, into inflamed meninges ranged between 4.37 and 7.53% (mean, 5.97%). Daptomycin was very efficacious in the treatment of experimental pneumococcal meningitis, producing a decrease of -1.20 +/- 0.32 Deltalog(10) CFU/ml. h in the bacterial titer of Streptococcus pneumoniae against a penicillin-resistant strain and of -0.97 +/- 0.32 Deltalog(10) CFU/ml. h against a penicillin- and quinolone-resistant strain found in cerebrospinal fluid (CSF). For both strains, daptomycin was significantly superior to the standard regimen of a combination of ceftriaxone with vancomycin, sterilizing 9 of 10 CSF samples after 4 h. In vitro, daptomycin produced highly bactericidal activity in concentrations above the MIC.

Animals↗
PubMed1990

Penicillin-resistant viridans streptococci have obtained altered penicillin-binding protein genes from penicillin-resistant strains of Streptococcus pneumoniae.

Penicillin-resistant strains of Streptococcus pneumoniae possess altered forms of penicillin-binding proteins (PBPs) with decreased affinity for penicillin. The PBP2B genes of these strains have a mosaic structure, consisting of regions that are very similar to those in penicillin-sensitive strains, alternating with regions that are highly diverged. Penicillin-resistant strains of viridans groups streptococci (e.g., S. sanguis and S. oralis) that produce altered PBPs have also been reported. The PBP2B genes of two penicillin-resistant clinical isolates of S. sanguis were identical in sequence to the mosaic class B PBP2B genes found in penicillin-resistant serotype 23 strains of S. pneumoniae. Emergence of penicillin resistance appears to have occurred by the horizontal transfer of an altered PBP2B gene from penicillin-resistant S. pneumoniae into S. sanguis. The PBP2B genes of three penicillin-resistant S. oralis strains were similar to the mosaic class B PBP2B gene of penicillin-resistant strains of S. pneumoniae but possessed an additional block of diverged sequence. Penicillin resistance in S. oralis has also probably arisen by horizontal transfer of this variant form of the class B mosaic PBP2B gene from a penicillin-resistant strain of S. pneumoniae.

Amino Acid Sequence↗
PubMed1997

Viridans streptococcal bacteraemia due to penicillin-resistant and penicillin-sensitive streptococci: analysis of risk factors and outcome in 60 patients from a single cancer centre before and after penicillin is used for prophylaxis.

60 patients with 60 viridans streptococcal bacteraemic episodes (42 due to penicillin-sensitive and 18 due to penicillin-resistant viridans streptococci) were analysed in a population of 12,185 admissions and 1,380 bacteraemic episodes during a 7-year period in a National Cancer Institute. The incidence of viridans streptococci among bacteraemias decreased from 11.5% in 1989 to 2.5% in 1995 after penicillin was introduced for prophylaxis of febrile neutropenia in acute leukaemia in 1993. However, the proportion of penicillin-resistant viridans streptococcal bacteraemias increased from 0 in 1989 and 1990 before any prophylaxis was given, to 12.9-16.7% after quinolones were used for prophylaxis in 1991 and 1992, and to 44.4-81.8% in 1993-1995 after penicillin was added to the quinolones. Mortality rate was higher in the subgroup of penicillin-resistant viridans streptococcal bacteraemias (p < 0.05). Statistically significant risk factors in patients with penicillin-resistant (compared with penicillin-sensitive) viridans streptococcal bacteraemia were: acute leukaemia (p < 0.03), high doses of cytarabine (p < 0.05), mucocutaneous lesions (p < 0.004), breakthrough bacteraemia during prophylaxis with ofloxacine plus penicillin (p < 0.001). Multiple logistic regression analysis showed that only acute leukaemia (OR 2.05, CI 0.85-1.85, p < 0.00452) and penicillin-resistance (OR 0.71, CI 0.103-4.887, p < 0.0209) were significant independent predictors of inferior outcome. Breakthrough bacteraemia during empiric therapy with vancomycine occurred in 5 of 116 patients treated with vancomycine, and during therapy with ampicillin plus gentamicin in 6 patients of 18 treated.

Acute Disease↗
PubMed2002

The 2.4-A crystal structure of the penicillin-resistant penicillin-binding protein PBP5fm from Enterococcus faecium in complex with benzylpenicillin.

Penicillin-binding proteins (PBPs) are membrane proteins involved in the final stages of peptidoglycan synthesis and represent the targets of beta-lactam antibiotics. Enterococci are naturally resistant to these antibiotics because they produce a PBP, named PBP5fm in Enterococcus faecium, with low-level affinity for beta-lactams. We report here the crystal structure of the acyl-enzyme complex of PBP5fm with benzylpenicillin at a resolution of 2.4 A. A characteristic of the active site, which distinguishes PBP5fm from other PBPs of known structure, is the topology of the loop 451-465 defining the left edge of the cavity. The residue Arg464, involved in a salt bridge with the residue Asp481, confers a greater rigidity to the PBP5fm active site. In addition, the presence of the Val465 residue, which points into the active site, reducing its accessibility, could account for the low affinity of PBP5fm for beta-lactam. This loop is common to PBPs of low affinity, such as PBP2a from Staphylococcus aureus and PBP3 from Bacillus subtilis. Moreover, the insertion of a serine after residue 466 in the most resistant strains underlines even more the determining role of this loop in the recognition of the substrates.

Amino Acid Sequence↗
PubMed1993

High-level penicillin resistance and penicillin-gentamicin synergy in Enterococcus faecium.

Thirty-seven Enterococcus faecium strains with different levels of penicillin susceptibility were studied in time-kill experiments with a fixed concentration (5 micrograms/ml) of gentamicin combined with different penicillin concentrations (6 to 600 micrograms/ml). Synergy was defined as a relative decrease in counts of greater than 2 log10 CFU per milliliter after 24 h of incubation when the combination of the antibiotics was compared with its most active component alone. The minimal synergistic penicillin concentrations found were 6 micrograms/ml for 16 of 16 strains for which penicillin MICs were < or = 25 micrograms/ml, 20 to 100 micrograms/ml for 14 of 17 strains for which penicillin MICs were 50 to 200 micrograms/ml, and 200 to 500 micrograms/ml for 4 of 4 strains for which MICs penicillin were > 200 micrograms/ml. Penicillin-gentamicin synergy was observed even in high-level penicillin-resistant E. faecium strains at penicillin concentrations close to one-half the penicillin MIC. The possibility of treating infections caused by high-level penicillin-resistant E. faecium strains with penicillin-gentamicin combinations in particular cases may depend on the penicillin levels attainable in vivo.

Drug Synergism↗
PubMed1995

Comparison of the response to antimicrobial therapy of penicillin-resistant and penicillin-susceptible pneumococcal disease.

The continued spread of penicillin-resistant pneumococci raises therapeutic concerns. Optimal therapy for resistant infections is unknown and it is not clear whether the efficacy of penicillin or equally active beta-lactam agents is compromised in non-meningeal-resistant infections. A prospective nonintervention study was undertaken to compare the clinical response in penicillin-resistant vs. penicillin-susceptible bacteremic pneumococcal infections, excluding meningitis. Of 108 children enrolled, 35 (32%) had penicillin-resistant (one highly resistant) isolates. Seventy-eight children had pneumonia, 21 had occult bacteremia (sepsis) and 9 had peritonitis. Children with resistant infections were more likely to have underlying disorders, especially human immunodeficiency virus infection, and to have received antimicrobial therapy in the previous month. After 48 hours of therapy 64% of penicillin-susceptible infections showed improvement vs. 60% of penicillin-resistant infections (odds ratio, 1.2; 95% confidence intervals, 0.5 to 3.0). In children with pneumonia treated with ampicillin or an equivalent beta-lactam agent, 93% with penicillin-susceptible infections had improved by Day 7 of therapy compared with 88% with resistant infections (odds ratio, 1.9; 95% confidence interval 0.3 to 15.9). The durations of respiratory distress, fever and oxygen requirement were similar in penicillin-susceptible and -resistant infections. These results suggest that intermediate penicillin resistance is of little significance in pneumococcal pneumonia or sepsis and that standard beta-lactam therapy is still highly effective. Further studies of highly penicillin-resistant infections are necessary.

Bacteremia↗
PubMed2003

Meropenem prevents levofloxacin-induced resistance in penicillin-resistant pneumococci and acts synergistically with levofloxacin in experimental meningitis.

The aim of the present study was to investigate the potential synergy between meropenem and levofloxacin in vitro and in experimental meningitis and to determine the effect of meropenem on levofloxacin-induced resistance in vitro. Meropenem increased the efficacy of levofloxacin against the penicillin-resistant pneumococcal strain KR4 in time-killing assays in vitro and acted synergistically against a second penicillin-resistant strain WB4. In the checkerboard, only an additive effect (FIC indices: 1.0) was observed for both strains. In cycling experiments in vitro, levofloxacin alone led to a 64-fold increase in the MIC for both strains after 12 cycles. Addition of meropenem in sub-MIC concentrations (0.25 x MIC) completely inhibited the selection of levofloxacin-resistant mutants in WB4 after 12 cycles. In KR4, the addition of meropenem led to just a twofold increase in the MIC for levofloxacin after 12 cycles. Mutations detected in the genes encoding for topoisomerase IV (parC) and gyrase (gyrA) confirmed the levofloxacin-induced resistance in both strains. Addition of meropenem was able to completely suppress levofloxacin-induced mutations in WB4 and led to only one mutation in parE in KR4. In experimental meningitis, meropenem, given in two doses (2 x 125 mg/kg), produced a good bactericidal activity (-0.45 Deltalog10 cfu/ml.h) comparable to one dose (1 x 10 mg/kg) of levofloxacin (-0.44 Deltalog10 cfu/ml.h) against the penicillin-resistant strain WB4. Meropenem combined with levofloxacin acted synergistically (-0.93 Deltalog10 cfu/ml.h), sterilizing the CSF of all rabbits.

Animals↗
PubMedDate not supplied

Comparative susceptibility of Yersinia enterocolitica, Eikenella corrodens, and penicillin-resistant and penicillin-susceptible Streptococcus pneumoniae to beta-lactam and alternative antimicrobial agents.

The antimicrobial susceptibilities were determined for 14 strains of Yersinia enterocolitica, 28 strains of Eikenella corrodens, 10 strains of penicillin-resistant Streptococcus pneumoniae, and 10 strains of penicillin-susceptible S. pneumoniae. Y. enterocolitica was found to be susceptible to the aminoglycosides tested and to chloramphenicol, moxalactam, cefoperazone, and cefotaxime but resistant to ampicillin and variably susceptible to carbenicillin, cefoxitin, and cefazolin. On a weight basis, cefotaxime and moxalactam were the most active agents against E. corrodens. Most strains of E. corrodens were resistant to the aminoglycosides tested: gentamicin, tobramycin, kanamycin, and amikacin. Penicillin-resistant S. pneumoniae was most susceptible to cefotaxime and moxalactam. Cefotaxime was consistently active against all tested strains of Y. enterocolitica, E. corrodens, and penicillin-resistant S. pneumoniae, three unusual but clinically significant pathogens.

Aminoglycosides↗
PubMed2004

Ceftriaxone acts synergistically with levofloxacin in experimental meningitis and reduces levofloxacin-induced resistance in penicillin-resistant pneumococci.

Ceftriaxone acted synergistically with levofloxacin in time-killing assays in vitro over 8 h against two penicillin-resistant pneumococcal strains (WB4 and KR4; MIC of penicillin: 4 mg/L). Synergy was confirmed with the chequerboard method, showing FIC indices of 0.25. In the experimental rabbit meningitis model, ceftriaxone (1x 125 mg/kg) was slightly less bactericidal (-0.30 Deltalog(10) cfu/mL(.)h) compared with levofloxacin (-0.45 Deltalog(10) cfu/mL(.)h) against the penicillin-resistant strain WB4. The combination therapy (levofloxacin and ceftriaxone) was significantly superior (-0.64 Deltalog(10) cfu/mL(.)h) to either monotherapy. In cycling experiments in vitro, the addition of ceftriaxone at a sub-MIC concentration (1/16 MIC) reduced levofloxacin-induced resistance in the two strains KR4 and WB4. After 12 cycles with levofloxacin monotherapy, the MIC increased 64-fold in both strains versus a 16-fold increase with the combination (levofloxacin + ceftriaxone 1/16 MIC). In both strains, levofloxacin-induced resistance was confirmed by mutations detected in the genes parC and gyrA, encoding for subunits of topoisomerase IV and gyrase, respectively. The addition of ceftriaxone suppressed mutations in parC but led to a new mutation in parE in both strains.

Animals↗
PubMed1985

Divergent disk susceptibility of coagulase-negative staphylococci to penicillinase-resistant penicillins and augmentin (amoxycillin/clavulanic acid).

30 representative intrinsically penicillin-resistant coagulase-negative staphylococcal (CONS) isolates yielded discrepant agar disk diffusion test (Bauer-Kirby) results for augmentin. Clavulanic acid (2.5 micrograms/ml) enhanced the activity of amoxycillin from 8- to greater than or equal to 128-fold (mean = 26-fold); MICs of amoxycillin (combined with 2.5 micrograms/ml clavulanate) ranged from 1-16 (mean = 3) micrograms/ml. It is recommended that clinical microbiology laboratories withhold 'susceptible' augmentin disk tests results from their reports regarding intrinsically penicillin-resistant CONS isolates. No such discrepancies were encountered among clinical isolates of Staphylococcus aureus.

Amoxicillin↗
PubMed1999

Increase in penicillin resistance rates in Belgium due to clonal spread of a penicillin-resistant 23F Streptococcus pneumoniae strain.

In 1994 a sudden increase in penicillin resistance was observed in Belgium among invasive pneumococci. To determine whether this increase was due to clonal spread of a resistant strain or to de novo acquisition of penicillin resistance, pneumococci of capsular types 23F, 19, 14, 9, and 6 isolated in 1993 and 1994, were analyzed by capsular serotyping and DNA macrorestriction analysis, resolved by pulsed-field gel electrophoresis. Furthermore, pneumococcal isolates from northern France, a region with a high prevalence of penicillin resistance, and from southern Belgium, a region with a low but increasing prevalence of penicillin resistance, were analyzed. The rate of resistance of invasive pneumococci to penicillin increased from 2.3% in 1993 to 7.6% in 1994. Pneumococcal serotype 23F represented 26.7% of the penicillin-resistant isolates in 1993 and 40.4% in 1994, while the prevalence of serotype 23F decreased from 10.9% in 1993 to 8.8% in 1994. In 1994 up to 35.8% of serotype 23F isolates were penicillin resistant. The Belgian penicillin-resistant 23F isolates from 1994 were genetically closely related to the French 23F penicillin-resistant isolates and, as clones were clearly distinct from the other serotypes as well as from the penicillin-susceptible 23F isolates. These data demonstrate the important contribution of the clonal spread of a penicillin-resistant pneumococcal strain in the overall increase of penicillin resistance in our country.

Belgium↗