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At least 19 recordsLinked to original sources
PubMed1994

Disposition of penicillin G after administration of benzathine penicillin G, or a combination of benzathine penicillin G and procaine penicillin G in cattle.

Plasma concentration of penicillin G was evaluated in beef steers after administration of either a combination of benzathine penicillin G and procaine penicillin G in a 1:1 mixture at a dosage of 9,000 U/kg of body weight, IM (n = 5), 24,000 U/kg, IM (n = 5), or 8,800 U/kg, SC (n = 5), or benzathine penicillin G alone at a dosage of 12,000 U/kg, IM (n = 7). Plasma concentration of penicillin G was measured by use of a high-performance liquid chromatography assay that had a limit of determination of 0.005 microgram/ml. At a dosage for this combination of 9,000 U/kg IM, and 8,800 U/kg, SC, which are approved label recommendations in Canada, and the United States, respectively, mean (+/- SEM) peak plasma concentration was 0.58 (+/- 0.15) and 0.44 (+/- 0.02) microgram/ml, respectively. Although plasma penicillin concentration was quantifiable for 7 days in the steers that received 9,000 U/kg, IM, and for 4 days in the steers that received 8,800 U/kg, SC, the concentration was < 0.1 microgram/ml in both groups after the first 12 hours. After administration of the combination at dosage of 24,000 U/kg, IM, there was an initial peak plasma concentration at approximately 2 hours; thereafter, plasma concentration decreased slowly, with half-life of 58 hours. Although plasma penicillin G concentration was quantifiable for 12 days at this dosage, concentration was < 0.1 microgram/ml after the first 48 hours. After the initial 48 hours, plasma concentration of penicillin was of similar magnitude and decreased at similar rate for the combination at dosage of 24,000 U/kg and for 12,000 U/kg of benzathine penicillin G alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Lack of penicillin resensitization in patients with a history of penicillin allergy after receiving repeated penicillin courses.

BACKGROUND: Up to 10% of the population reports an allergy to penicillin, yet more than 80% of these individuals lack penicillin-specific IgE antibodies. A negative result on a penicillin skin test is highly accurate in identifying who can safely receive the antibiotic at the time of testing. However, its negative predictive value for future courses is unknown because it is uncertain whether patients with a history of penicillin allergy are at risk of becoming resensitized. OBJECTIVE: To determine the rate of penicillin resensitization in adult patients with a history of penicillin allergy after they are challenged with repeated courses of oral penicillin. METHODS: Adult patients with a history of penicillin allergy consistent with an IgE-mediated mechanism were recruited and underwent penicillin skin testing. Those with negative skin test results were challenged with 3 successive 10-day courses of penicillin V potassium (250 mg by mouth 3 times a day), providing their penicillin skin test results remained negative prior to each course. Patients with positive skin test results were not challenged. RESULTS: Of 53 patients with initially negative skin test results, 46 completed the protocol, and each tolerated all 3 courses of penicillin with negative skin test results throughout. No patients had a converted skin test result from negative to a positive, yielding a resensitization rate of 0% (upper 95% confidence interval, 2.1%). CONCLUSIONS: Adult patients with a history of penicillin allergy are not at increased risk of resensitization after receiving 3 courses of oral penicillin. Because a negative penicillin skin test result is predictive for subsequent oral administrations beyond the time of testing, adult patients with a history of penicillin allergy can be skin tested electively, which may avoid unnecessary treatment with alternate broad-spectrum antibiotics.

Adult↗
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↗
PubMed2002

Value of Etest penicillin V and penicillin G strips for penicillin susceptibility testing of Neisseria meningitidis.

The NCCLS agar dilution method and Etest are currently accepted methods for susceptibility testing of Neisseria meningitidis to penicillin. We determined the MIC of penicillin V and penicillin G by both the agar dilution method and Etest using 43 strains of N. meningitidis. Although results for reference strains were within the accepted quality control range of penicillin MICs for both drugs, differences of two to three dilutions were seen between the two antibiotics with both methods. Penicillin V results cannot correctly predict the susceptibility to penicillin G for N. meningitidis if penicillin G breakpoints are used for penicillin V. However, adjusting the penicillin V breakpoints two dilutions higher (i.e., S < or = 0.25 and R > or = 8 microg/ml), concordance could be achieved for susceptibility categorization by the two compounds. An agreement of 98% +/- 1 dilution was obtained between Etest and the reference method when using penicillin G strips. We conclude that Etest with penicillin G strips is a convenient and reliable alternative method for determining the MICs of penicillin for N. meningitidis.

Culture Media↗
PubMed1997

Experimental lobar pneumonia due to penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae in immunocompetent and neutropenic rats: efficacy of penicillin and teicoplanin treatment.

Lobar pneumonia models were established in rats by intratracheal inoculation of either penicillin-susceptible (immunocompetent model) or penicillin-resistant (immunocompetent and neutropenic models) Streptococcus pneumoniae. Untreated animals maintained a relatively high bacterial load in the lungs but only occasionally developed bacteraemia or pleurisy. The infection was rarely fatal in immunocompetent rats, but immunocompromised rats frequently died. Treatment i.m. with 10,000 IU/kg of procaine penicillin G (12 h after infection then bid for 3 days) or with a single i.v. dose of 5 or 10 mg/kg of teicoplanin significantly reduced lung bacterial loads of rats infected with the penicillin-susceptible strain. Against the penicillin-resistant strain, teicoplanin displayed a significant activity regardless of the immununological status of the animals. Penicillin G significantly reduced lung bacterial load of the penicillin-resistant strain only in immunocompetent rats and at a higher dose than needed in treatment of the penicillin-susceptible infection. The experimental models described here could be suitable for studying the efficacy of antibacterial agents against pulmonary infections caused by penicillin-susceptible and penicillin-resistant S. pneumoniae strains.

Animals↗
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↗
PubMedDate not supplied

Depletion of penicillin G residues in tissues and injection sites of yearling beef steers dosed with benzathine penicillin G alone or in combination with procaine penicillin G.

The contribution of benzathine penicillin G to residues in tissues and injection sites of yearling beef steers was assessed by treating seven groups of five to seven steers with either benzathine and procaine penicillin G together or benzathine penicillin G alone. Steers were injected with a commercial combination of benzathine and procaine penicillin G according to the Canadian (intramuscular) or United States (subcutaneous) label dosages of 8600 and 8800 IU penicillin G/kg body weight, respectively. They were killed 14 or 30 days after the intramuscular injections, and 30 days after the subcutaneous injections. At the label withdrawal times, Canadian 14 days and United States 30 days, the levels in the injection sites for all of the treatments were 30-60 times above the Canadian and United States' Maximum Residue Limit of 50 micrograms/kg, while liver, kidney and gluteal muscle levels were below the Maximum Residue Limit. Other steers were injected intramuscularly with 24,000 IU benzathine/procaine penicillin G/kg body weight and slaughtered 8, 14 or 50 days after injection. Fifty-day injection site residues were 24 times the Maximum Residue Limit. Another group of steers was injected intramuscularly with benzathine penicillin G alone at 12,000 IU/kg body weight and slaughtered 14 days later. Penicillin G levels in the injection sites were 156 times the Maximum Residue Limit. The persistence of penicillin G residues at the injection sites in all the treatment groups appears to be attributable primarily to benzathine penicillin G. Visual inspection of muscle surfaces did not reliably reveal all injection site lesions in the underlying musculature.

Animals↗
PubMed1987

Efficacy of beta-lactamase-resistant penicillin and influence of penicillin tolerance in eradicating streptococci from the pharynx after failure of penicillin therapy for group A streptococcal pharyngitis.

We studied the ability of dicloxacillin, a beta-lactamase-resistant penicillin, to eradicate persistent group A streptococci from the upper respiratory tract of children previously given penicillin V, and concomitantly assessed the role of antibiotic (penicillin and dicloxacillin) tolerance as a contributing factor. During a group A streptococcal pharyngitis outbreak, 66% of 324 children were found to be culture positive for group A streptococci. Ninety percent of these isolates were serotype M-1, T-agglutination pattern T-1. The treatment failure rate after initial orally administered penicillin treatment was 21% (42 of 204). These 42 children then received either a second course of penicillin V orally or a course of dicloxacillin. The resulting rates of failure to eradicate the homologous streptococcal serotype were 83% (20 of 24) and 50% (9 of 18), respectively (P less than 0.02). Of 189 streptococcal isolates tested by the gradient replicate plate method for penicillin tolerance, 18 (10%) were tolerant. In this study, penicillin-tolerant strains of group A streptococci were no more frequently isolated from children in whom initial penicillin treatment failed than from those who were successfully treated. Dicloxacillin tolerance was not a factor in failure of dicloxacillin therapy. These data, when evaluated with data from previous studies, suggest that reasons for failure to eradicate group A streptococci from the upper respiratory tract are complex, but dicloxacillin may be beneficial in some patients who fail to respond to orally administered penicillin therapy.

Child↗
PubMed2002

Effects of amino acid alterations in penicillin-binding proteins (PBPs) 1a, 2b, and 2x on PBP affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor in 18 clinical isolates of penicillin-susceptible, -intermediate, and -resistant pneumococci.

Amino acid alterations in or flanking conserved motifs making up the active binding sites of penicillin-binding proteins (PBPs) 1a, 2b, and 2x of pneumococci were correlated with changes in affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor for these PBPs. Four penicillin-susceptible (PSSP), eight penicillin-intermediate (PISP), and six penicillin-resistant (PRSP) pneumococci were studied by DNA sequencing of the penicillin-binding sites of the pbp1a, -2x, and -2b genes of strains and by determining 50% inhibitory concentrations of the seven agents for PBP1a, -2x, and -2b. Two PSSP strains had alterations in PBP2x (L(546)-->V) (one strain) or PBP2b (T(445)-->A) (one strain). All eight PISP strains had at least two alterations--T(338)-->P or A or H(394)-->Y in PBP2X and T(445)-->A in BPB2b. All PRSP strains had the same changes seen in PISP strains, as well as T(371)-->A or S substitutions in PBP1a. The two most resistant PRSP strains had a second change in PBP2x (M(339)-->F) in a conserved motif. The affinities of penicillin and ampicillin for all three PBPs were decreased for PRSP and most PISP strains. The affinity of amoxicillin for PBP1a and -2x was decreased only for PRSP. Cefaclor and cefprozil showed decreased affinity of PRSP but not PISP for all three PBPs. Cefuroxime showed decreased affinity of PISP and PRSP for PBP1a and -2x but no change for PBP2b. Cefditoren showed no difference in PBP affinity based on penicillin or cefditoren MICs, indicating a different PBP target for this agent. Overall, the MICs for and PBP affinities of the strains correlated with the changes found in the PBP active binding sites.

Adult↗
PubMed1984

Serum concentration of penicillin in the horse after repeated intramuscular injections of procaine penicillin G alone or in combination with benzathine penicillin and/or phenylbutazone.

Twenty-one adult horses were randomly assigned into 7 groups of 3 and were treated for 5 days with procaine penicillin G, benzathine penicillin , or phenylbutazone in various combinations and dosage schedules. Serum concentration of penicillin was measured serially over a 7-day period. The highest mean peak serum concentration was 2.06 micrograms/ml. Comparable peak values were seen 2 to 4 hours after administration of 22,000 IU of procaine penicillin G/kg of body weight given once or twice daily. A minimum serum concentration of 0.25 micrograms/ml was selected as adequate for efficacy against organisms that can be considered sensitive to penicillin. Once daily administration of procaine penicillin G and, although peak concentrations were lower, some regimens of procaine and benzathine penicillin G did maintain this concentration. Concurrent phenylbutazone administration did not affect serum concentration of penicillin appreciably.

Animals↗
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↗
PubMed1990

Clindamycin vs penicillin for anaerobic lung infections. High rate of penicillin failures associated with penicillin-resistant Bacteroides melaninogenicus.

Thirty-seven adult patients with anaerobic lung infections (27 lung abscesses and 10 necrotizing pneumonias) were submitted to transthoracic needle-aspiration and/or bronchoscopic specimen brush cultures before therapy and thereafter in all cases considered to be failures. Patients were randomly assigned to receive either clindamycin, 600 mg intravenously every 6 hours, or penicillin G, 2 million U every 4 hours for no less than 8 days, until clinical and radiological improvement became apparent. Treatment was continued orally with clindamycin, 300 mg every 6 hours, or penicillin V, 750 mg every 6 hours, until completing a minimum of 4 weeks. Ten of the 47 anaerobes initially isolated from the lung (nine Bacteroides melaninogenicus and one Bacteroides capillosus) were resistant to penicillin, but none were resistant to clindamycin. Five of the nine patients harboring these penicillin-resistant Bacteroides received penicillin, and all failed to respond to therapy. Overall, eight of the 18 patients in the penicillin group and one of 19 in the clindamycin group failed to respond to therapy. These drugs were equally well tolerated in both groups. The presence of penicillin-resistant Bacteroides is a frequent cause of penicillin failure in patients with anaerobic lung infections. In this setting, clindamycin appears to be the current therapy of choice for initial treatment.

Adult↗