Showing papers on "Penicillin published in 1990"
TL;DR: Enterococci are important human pathogens that are increasingly resistant to antimicrobial agents, including resistance to cephalosporins, clindamycin, tetracycline, and penicillinase-resistant penicillins such as oxacillin, among others.
Abstract: Enterococci are important human pathogens that are increasingly resistant to antimicrobial agents. These organisms were previously considered part of the genus Streptococcus but have recently been reclassified into their own genus, called Enterococcus. To date, 12 species pathogenic for humans have been described, including the most common human isolates, Enterococcus faecalis and E. faecium. Enterococci cause between 5 and 15% of cases of endocarditis, which is best treated by the combination of a cell wall-active agent (such as penicillin or vancomycin, neither of which alone is usually bactericidal) and an aminoglycoside to which the organism is not highly resistant; this characteristically results in a synergistic bactericidal effect. High-level resistance (MIC, greater than or equal to 2,000 micrograms/ml) to the aminoglycoside eliminates the expected bactericidal effect, and such resistance has now been described for all aminoglycosides. Enterococci can also cause urinary tract infections; intraabdominal, pelvic, and wound infections; superinfections (particularly in patients receiving expanded-spectrum cephalosporins); and bacteremias (often together with other organisms). They are now the third most common organism seen in nosocomial infections. For most of these infections, single-drug therapy, most often with penicillin, ampicillin, or vancomycin, is adequate. Enterococci have a large number of both inherent and acquired resistance traits, including resistance to cephalosporins, clindamycin, tetracycline, and penicillinase-resistant penicillins such as oxacillin, among others. The most recent resistance traits reported are penicillinase resistance (apparently acquired from staphylococci) and vancomycin resistance, both of which can be transferred to other enterococci. It appears likely that we will soon be faced with increasing numbers of enterococci for which there is no adequate therapy.
1,817 citations
TL;DR: The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin.
Abstract: The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin. Multiply resistant pneumococci are being encountered more commonly and are more often community acquired. Factors associated with infection caused by resistant pneumococci include young age, duration of hospitalization, infection with a pneumococcus of serogroup 6, 19, or 23 or serotype 14, and exposure to antibiotics to which the strain is resistant. At present, the most useful drugs for the management of resistant pneumococcal infections are cefotaxime, ceftriaxone, vancomycin, and rifampin. If the strains are susceptible, chloramphenicol may be useful as an alternative, less expensive agent. Appropriate interventions for the control of resistant pneumococcal outbreaks include investigation of the prevalence of resistant strains, isolation of patients, possible treatment of carriers, and reduction of usage of antibiotics to which the strain is resistant. The molecular mechanisms of penicillin resistance are related to the structure and function of penicillin-binding proteins, and the mechanisms of resistance to other agents involved in multiple resistance are being elucidated. Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk.
844 citations
TL;DR: A national surveillance study was conducted to determine trends in antimicrobial resistance patterns among three common causes of community-acquired respiratory tract infections, and the lowest resistance rates for these common bacterial respiratory pathogens were noted with amoxicillin-clavulanate, cefuroxime, and cefaclor.
Abstract: A national surveillance study was conducted to determine trends in antimicrobial resistance patterns among three common causes of community-acquired respiratory tract infections. Fifteen participating U.S. medical centers submitted clinically significant isolates of Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and Streptococcus pneumoniae to two central laboratories for testing with a group of 12 antimicrobial agents. The majority of isolates were recovered from adult males greater than 50 years old. Overall, 84.1% of 378 M. catarrhalis and 16.5% of 564 H. influenzae (29.5% of type b strains; 15.0% of non-type b strains) produced beta-lactamase and were thus resistant to penicillin, ampicillin, and amoxicillin. Resistance in H. influenzae to other agents was 2.1% to tetracycline, 0.7% to trimethoprim-sulfamethoxazole, 1.1% to cefaclor, and 0.2% to cefuroxime and amoxicillin-clavulanate, while the M. catarrhalis isolates yielded very low MICs of these latter drugs. As demonstrated in prior studies, erythromycin showed little activity against H. influenzae. Of 487 S. pneumoniae isolates, 1 (0.2%) was penicillin resistant, while 3.8% were relatively resistant to penicillin, 4.5% were resistant to trimethoprim-sulfamethoxazole, 2.3% were resistant to tetracycline, 1.2% were resistant to chloramphenicol, and 0.2% were resistant to erythromycin. Overall, the lowest resistance rates for these common bacterial respiratory pathogens were noted with amoxicillin-clavulanate, cefuroxime, and cefaclor.
310 citations
TL;DR: The prevalence of pneumococcal resistance in Spain is, as far as the authors know, among the highest published to date.
Abstract: Serotypes and antibiotic susceptibilities were determined for 2,197 Streptococcus pneumoniae strains isolated from patients with systemic infections over an 11-year period. The predominant serogroups and serotypes, in order of decreasing frequency, were 3, 6, 23, 19, 9, 1, 5, 8, 7, 14, 4, and 15; these types accounted for more than 75% of the strains studied. Altogether, 93% of the pneumococci belonged to groups or types included in the 23-valent pneumococcal vaccine. Overall, 65.5% of pneumococci were resistant to one or more drugs. The incidence of penicillin-resistant pneumococci rose from 6% in 1979 to 44% in 1989, and the degree of penicillin resistance also increased throughout the study. Overall, the resistance rates were 28% for penicillin, 56% for tetracycline, 43% for chloramphenicol, and 5% for erythromycin. Seventy-one pneumococcal isolates resistant to all four antibiotics tested were found. The prevalence of pneumococcal resistance in Spain is, as far as we know, among the highest published to date.
308 citations
TL;DR: IT testing should be used instead of disk diffusion testing for vancomycin-resistant gram-positive bacteria from three genera, because few very major or major errors were obtained, but the number of minor errors was 19.3%.
Abstract: Eighty-five strains of vancomycin-resistant gram-positive bacteria from three genera, Leuconostoc, Pediococcus, and Lactobacillus, were tested to determine susceptibility to 24 antimicrobial agents by broth microdilution and to 10 agents by disk diffusion. The MICs of vancomycin and teicoplanin ranged from 64 to greater than 512 micrograms/ml; however, the MICs of daptomycin, a new lipopeptide, were all less than or equal to 0.25 micrograms/ml. None of the organisms were resistant to imipenem, minocycline, chloramphenicol, gentamicin, or daptomycin. The MICs of penicillin were in the moderately susceptible range for all but three strains. Susceptibility to the other agents varied by genus and, in some cases, by species. When disk diffusion results were compared with MICs for drugs recommended for streptococci by the National Committee for Clinical Laboratory Standards, Villanova, Pa., few very major or major errors were obtained, but the number of minor errors was 19.3%. Therefore, we recommended that MIC testing be used instead of disk diffusion testing for these organisms.
211 citations
TL;DR: 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.
Abstract: 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 (eg, 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
207 citations
TL;DR: The challenge tests suggested that not all the penicillin‐sensitive subjects had IgE‐mediated reactions implying other immunological mechanisms, demonstrating the importance of side chain‐specific diagnostic reagents and challenge tests.
Abstract: Two hundred and eighty-eight subjects with a history of allergy to penicillin were studied for objective proof of their allergy. On the basis of skin tests, specific IgE antibody measurements and direct challenge tests. 64 patients (22%) were shown objectively to be allergic to one or more penicillins. The following tests were carried out: skin tests to benzyl-penicilloyl poly-L-lysine (BPO-PLL), minor determinant mixture (MDM), amoxycillin (AX) and ampicillin (AMP), in-vitro IgE antibody measurement to benzyl-penicilloyl (BPO) and AX and challenge with benzylpenicillin (BP), phenoxy-methyl-penicillin (PV) and amoxycillin. Forty-four cases were found to respond to benzyl or phenoxymethyl-penicillin, however, 20 were shown to be sensitive to amoxycillin and unresponsive to tests with other penicillins. The contribution that any individual test gave for establishing the diagnosis was 21.8% for skin testing with BPO-PLL, 9.3% with MDM and 12.5% with AX. Nine point three per cent were RAST positive to BPO and 1.5% to AX; 7.8% developed a positive response after challenge to BP, 7.8% to PV and 14% to AX. In 16% of the 64 positive cases more than one test was found to be positive. The challenge tests suggested that not all the penicillin-sensitive subjects had IgE-mediated reactions implying other immunological mechanisms. These results clearly demonstrate the importance of side chain-specific diagnostic reagents and challenge tests. Thirty-one per cent of the positive group or 6.9% of the total group would have been missed in this study using benzyl or phenoxymethyl-penicillin diagnostic reagents alone.
183 citations
TL;DR: It is suggested that the remodeling of the active site of penicillin binding proteins in the resistant bacteria, which results in the reduced affinity forPenicillin, also changes the substrate preference of these enzymes for the more hydrophobic branched peptides (instead of linear peptides) for cell wall synthesis.
Abstract: Pneumococcal strains with greatly elevated levels of resistance to penicillin have by now been described with increasing frequency worldwide. The mechanism of antibiotic resistance in these strains involves the molecular remodeling of cell wall synthetic enzymes (penicillin binding proteins). We have now analyzed the peptidoglycan structures of 10 penicillin-susceptible and 10 penicillin-resistant clinical isolates (4 of intermediate and 6 of high level resistance) with a high-resolution HPLC technique. Cell wall peptidoglycan of the susceptible strains contained monomeric and oligomeric forms of primarily (70% or more) linear stem peptides with the sequence of L-Ala-D-iGln-L-Lys-D-Ala (where iGln is isoglutamine). In contrast, the major peptide species (70% or more) of resistant cell walls were abnormal branched-stem peptides carrying Ala-Ser or Ala-Ala dipeptides on the epsilon-amino groups of the stem peptide lysine residues. The structural alteration in the peptidoglycan was not related to serotype, date, or site of isolation but showed strong correlation with penicillin resistance and was cotransformed with high-level penicillin resistance during genetic transformation. We suggest that the remodeling of the active site of penicillin binding proteins in the resistant bacteria, which results in the reduced affinity for penicillin, also changes the substrate preference of these enzymes for the more hydrophobic branched peptides (instead of linear peptides) for cell wall synthesis.
148 citations
TL;DR: The results demonstrate the wide distribution of antimicrobial-resistant N gonorrhoeae and support recent changes in Centers for Disease Control therapy recommendations for gonococcal infections that no longer recommend tetracycline and penicillin as first-line therapies.
Abstract: The Gonococcal Isolate Surveillance Project is a national sentinel surveillance system to estimate levels and monitor trends of antimicrobial resistance in prospectively collected isolates of Neisseria gonorrhoeae . Of 6204 isolates evaluated from 21 clinic sites between September 1987 and December 1988, 21% met at least one of the surveillance criteria for resistance to penicillin, tetracycline, cefoxitin, or spectinomycin; 2.2% were penicillinase-producing N gonorrhoeae ; 1.0% had high-level plasmid-mediated tetracycline resistance; and 16.8% of the isolates without plasmid-mediated resistance had chromosomally mediated resistance (defined as a minimum inhibitory concentration ≥2 μg/mL) to penicillin, tetracycline, or cefoxitin. Three isolates were resistant to spectinomycin. All isolates were susceptible to ceftriaxone. Resistant isolates were identified from all participating centers. Patient demographic and behavioral characteristics were not predictive of infections caused by resistant organisms. These results demonstrate the wide distribution of antimicrobial-resistant N gonorrhoeae and support recent changes in Centers for Disease Control therapy recommendations for gonococcal infections that no longer recommend tetracycline and penicillin as first-line therapies. ( JAMA . 1990;264:1413-1417)
140 citations
TL;DR: The data suggests that genes encoding all the enzymes necessary for the biosynthesis of penicillin from amino acid precursors are closely linked in P. chrysogenum and constitute a gene cluster.
Abstract: A cosmid clone containing the putative penicillin biosynthetic gene cluster from Penicillium chrysogenum was used to transform the related filamentous fungi Neurospora crassa and Aspergillus niger, which do not produce beta-lactam antibiotics. Both of the transformed hosts contained intact P. chrysogenum DNA derived from the cosmid clone and produced authentic penicillin V. Assays of penicillin biosynthetic enzyme activity additionally demonstrated that they possessed delta-(L-alpha-amino-adipyl)-L-cysteinyl-D-valine synthetase (ACVS), isopenicillin N synthetase (IPNS) and acyl coenzyme A:6-aminopenicillanic acid acyltransferase (ACT) activity. The data suggests that genes encoding all the enzymes necessary for the biosynthesis of penicillin from amino acid precursors are closely linked in P. chrysogenum and constitute a gene cluster.
123 citations
TL;DR: Thirty-seven adult patients with anaerobic lung infections were submitted to transthoracic needle-aspiration and/or bronchoscopic specimen brush cultures before therapy and thereafter in all cases considered to be failures, and clindamycin appears to be the current therapy of choice for initial treatment.
Abstract: 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.
TL;DR: Clinical isolates that produce altered forms of PBP2 that differ from that of penicillin‐sensitive strains only in the insertion of Asp‐345A have been identified.
Abstract: Non-beta-lactamase-producing, penicillin-resistant strains of Neisseria gonorrhoeae (CMRNG strains) produce altered forms of penicillin-binding protein 2 (PBP2) that have decreased affinity for penicillin. A feature of PBP2 from all CMRNG strains is the presence of an additional residue (Asp-345A) that is absent from PBP2 of penicillin-sensitive strains. The role of the additional aspartic acid residue in the decreased affinity of PBP2 is unclear as PBP2 of all previously examined CMRNG strains possess several other amino acid sequence alterations, in addition to the insertion of Asp-345A, compared to PBP2 of penicillin-sensitive strains. Site-directed mutagenesis has been used to insert the Asp-345A codon into the penA gene from a penicillin-sensitive gonococcus. The resulting penA gene expressed an altered form of PBP2 that had a decreased affinity for benzylpenicillin and was able to transform a penicillin-sensitive strain of N. gonorrhoeae to an increased level of resistance to benzylpenicillin. Insertion of amino acids other than aspartic acid did not produce forms of PBP2 that provided increased resistance to penicillin. Removal of the Asp-345A codon from the penA gene of a CMRNG strain reduced its ability to transform a penicillin-sensitive strain to an increased level of penicillin resistance. The reduction in the affinity of PBP2 in CMRNG strains is therefore largely, although not exclusively, due to the insertion of Asp-345A. Clinical isolates that produce altered forms of PBP2 that differ from that of penicillin-sensitive strains only in the insertion of Asp-345A have been identified.
TL;DR: It is now apparent that differences in body composition and organ function significantly affect the pharmacokinetics of antibacterial drugs in neonates, and dosage modifications are required to optimise antimicrobial therapy.
Abstract: Neonatal patients are surviving longer due to the rapid advances in medical knowledge and technology. Our understanding of the developmental physiology of both preterm and full term neonates has also increased. It is now apparent that differences in body composition and organ function significantly affect the pharmacokinetics of antibacterial drugs in neonates, and dosage modifications are required to optimise antimicrobial therapy. The penicillins and cephalosporins are frequently used in neonates. Although ampicillin has replaced benzylpenicillin (penicillin G) for empirical treatment of neonatal sepsis, many of the other penicillins may be used in neonates for the management of various infections. Increased volume of distribution (Vd) and decreased total body clearance (CL) affect the disposition of penicillins and cephalosporins. Decreased renal clearance (CLR) due to decreased glomerular filtration and tubular secretion is responsible for the decreased CL for most of the beta-lactams. Aminoglycoside Vd is affected by the increased total body water content and extracellular fluid volume of neonates. The increased Vd, in part, accounts for the extended elimination half-life (t1/2) observed in neonates. Aminoglycoside CL is dependent on renal glomerular filtration which is markedly decreased in neonates, especially those preterm. These drugs appear to be less nephrotoxic and ototoxic in neonates than in older patients, and the role of serum concentration monitoring should be limited to specific neonatal patients. Other antibiotics such as vancomycin, teicoplanin, chloramphenicol, rifampicin, erythromycin, clindamycin, metronidazole and cotrimoxazole (trimethoprim plus sulfamethoxazole) may be used in certain clinical situations. The emergence of staphylococcal resistance to penicillins has increased the need for vancomycin. With the exceptions of vancomycin and chloramphenicol, the efficacy and safety of these other agents in neonates have not been established. The need for serum vancomycin concentration monitoring may be limited, as with aminoglycosides, while safety concerns warrant the routine monitoring of serum chloramphenicol concentrations in neonates. Dosing guidelines are provided, based on the pharmacokinetics of the drugs and previously published recommendations. These dosing guidelines are intended for initial therapy, and close therapeutic monitoring is recommended for maintenance dose requirements to optimise patient outcome. There has been an enormous increase in our knowledge of neonatal physiology and drug disposition. Fortunately, many of the antibacterial drugs used in neonates (e.g. penicillins and cephalosporins) are relatively safe. It will be important to evaluate all newly developed antibiotics in neonates to assure their maximum efficacy and safety.
TL;DR: The results demonstrate the wide distribution of antimicrobial-resistant N gonorrhoeae and support recent changes in Centers for Disease Control therapy recommendations for gonococcal infections that no longer recommend tetracycline and penicillin as first-line therapies.
Abstract: The Gonococcal Isolate Surveillance Project is a national sentinel surveillance system to estimate levels and monitor trends of antimicrobial resistance in prospectively collected isolates of Neisseria gonorrhoeae. Of 6204 isolates evaluated from 21 clinic sites between September 1987 and December 1988, 21% met at least one of the surveillance criteria for resistance to penicillin, tetracycline, cefoxitin, or spectinomycin; 2.2% were penicillinase-producing N gonorrhoeae; 1.0% had high-level plasmid-mediated tetracycline resistance; and 16.8% of the isolates without plasmid-mediated resistance had chromosomally mediated resistance (defined as a minimum inhibitory concentration greater than or equal to 2 micrograms/mL) to penicillin, tetracycline, or cefoxitin. Three isolates were resistant to spectinomycin. All isolates were susceptible to ceftriaxone. Resistant isolates were identified from all participating centers. Patient demographic and behavioral characteristics were not predictive of infections caused by resistant organisms. These results demonstrate the wide distribution of antimicrobial-resistant N gonorrhoeae and support recent changes in Centers for Disease Control therapy recommendations for gonococcal infections that no longer recommend tetracycline and penicillin as first-line therapies.
Journal Article•
TL;DR: Results suggest that outcome of treatment in patients with acute cholangitis is similar with either a broad spectrum penicillin or apenicillin plus aminoglycoside combination and is dependent upon the nature of the biliary obstruction.
Abstract: In a previous study of patients with acute cholecystitis, we demonstrated equal efficacy with a broad spectrum penicillin (piperacillin) and a penicillin plus amino-glycoside combination. Whether a single agent broad spectrum penicillin is adequate treatment for more severe infections, such as acute cholangitis, however, is still unclear. We, therefore, conducted a three center, prospective, randomized trial to determine whether or not a broad spectrum penicillin alone is adequate therapy for patients with acute cholangitis. During a 36 month period, 96 patients with sepsis and biliary obstruction were randomly assigned to receive either piperacillin (n = 49) or ampicillin plus tobramycin (n = 47). The two groups receiving antibiotics were similar with respect to all clinical and laboratory parameters. The incidence of blood cultures with positive results (20 versus 21 per cent) and underlying malignant lesions (51 versus 62 per cent) was also similar between the two groups. The percentage of patients with a clinical cure or significant improvement was the same in the two groups (69 versus 70 per cent). However, there was a significant difference in the cure rate between patients with benign and malignant biliary obstructions (83 versus 59 per cent, p less than 0.01). No significant differences were noted between the two antibiotic groups with respect to drug toxicity, but patients with malignant conditions were more prone to antibiotic related toxicities (2 versus 19 per cent, p less than 0.05). These data suggest that outcome of treatment in patients with acute cholangitis is similar with either a broad spectrum penicillin or a penicillin plus aminoglycoside combination and is dependent upon the nature of the biliary obstruction.
TL;DR: The data suggest that prolonged levels of aminoglycoside in serum might be important to exhibit the greatest in vivo efficacy of the combination against E. faecalis and indicate that use of a reduced total daily dose of am inoglycosid or an increase in the interval between each dose might reduce the efficacy of therapy in animals with this type of infection.
Abstract: The penicillin-aminoglycoside combination is recommended for the treatment of systemic enterococcal infections. However, the optimal dosing regimen of the aminoglycoside remains to be elucidated. We evaluated the efficacy of penicillin, alone or in combination with various dosing regimens of netilmicin, for the treatment of experimental left-sided Enterococcus faecalis endocarditis in rabbits. Animals were injected intramuscularly for 4 days with penicillin alone or in combination with netilmicin in one of the following regimens: netilmicin at a low dose (2 mg/kg of body weight every 8 h), netilmicin at a high dose (4 mg/kg every 8 h), or netilmicin at a single daily high dose (12 mg/kg every 24 h). MICs and MBCs were 3.1 and 6.2 micrograms/ml and 8 and 8 micrograms/ml for penicillin and netilmicin, respectively. A netilmicin concentration of 4 micrograms/ml was the lowest concentration that achieved synergism with penicillin, as shown by the kill-curve method. Mean peak levels of netilmicin in serum were 5.6 (netilmicin at 2 mg/kg), 9.8 (netilmicin at 4 mg/kg), and 20.6 (netilmicin at 12 mg/kg) micrograms/ml. Mean penicillin levels in serum were constantly above the MIC. Penicillin plus netilmicin at a high dose given three times daily was more effective (P less than 0.05) than any other regimen in reducing bacterial titers in vegetations and was the only treatment that induced a significant bactericidal activity in rabbit serum during the trough. We concluded that divided doses of aminoglycoside are more effective than the same total dose given once daily in combination with penicillin. Our data suggest that prolonged levels of aminoglycoside in serum might be important to exhibit the greatest in vivo efficacy of the combination against E. faecalis. They also indicate that use of a reduced total daily dose of aminoglycoside or an increase in the interval between each dose might reduce the efficacy of therapy in animals with this type of infection.
TL;DR: Azithromycin was shown to be as effective as standard benzathine penicillin and erythromycin in the therapy of active syphilis in the rabbit model, and Persistent infection was demonstrable in lymph nodes of untreated animals, but no evidence of virulent T. pallidum was found three months following transfer of tissue.
Abstract: Azithromycin was shown to be as effective as standard benzathine penicillin and erythromycin in the therapy of active syphilis in the rabbit model. Following production of primary chancres by intradermal inoculation of 10(6) Treponema pallidum, groups of six rabbits were treated with benzathine penicillin (200,000 units im weekly for two weeks), erythromycin base (30 mg/kg/day orally four times daily for 15 days) or azithromycin (30 mg/kg/day given orally once or twice daily for 15 days); one group was untreated. Daily darkfield (DF) microscopic examinations of chancre aspirates were conducted to identify motile organisms. Although all treated animals became DF negative prior to completion of therapy, the median time to DF negativity was longer in animals given azithromycin once daily, compared with animals receiving benzathine penicillin (P less than 0.01); no difference was seen in comparison with animals receiving erythromycin. Untreated animals remained DF positive for greater than 15 days. The mean maximum lesion diameters for all treated animals were similar and were significantly smaller than in untreated rabbits; fewer lesions ulcerated in treated than in untreated animals. Subsequent dose-ranging studies indicated that administration of lower doses of azithromycin (15 mg/kg/day given orally either once or twice daily, or 7.5 mg/kg/day given once daily) was as effective as benzathine penicillin for therapy of active syphilis in this model, though the median time to darkfield negativity was significantly longer in the azithromycin-treated animals (P less than 0.01). Persistent infection was demonstrable in lymph nodes of untreated animals, but no evidence of virulent T. pallidum was found three months following transfer of tissue from any animal treated with penicillin, erythromycin, or azithromycin.
TL;DR: Ceftriaxone ought to be preferred to oral penicillin in patients with more severe early Lyme borreliosis, but not in the overall evaluation of clinical, serological and bacteriological outcome data.
Abstract: In a prospective randomized multicenter trial for the therapy of erythema migrans, 40 patients received ceftriaxone 1 g daily for 5 days and 33 patients obtained phenoxymethylpenicillin, 1 million units 3 times daily, for 12 days. Follow-up was for a mean of 10±5 months. Eight oral penicillin recipients (24%) and six ceftriaxone recipients (15%) developed minor consecutive manifestations. Two ceftriaxone and one penicillin recipient(s) still had elevated IgG antibody titers 10 to 20 months after therapy.Borrelia burgdorferi could be isolated from the erythema migrans in 29 out of 56 patients (52%) before therapy and in one oral penicillin recipient but none of 24 other patients after therapy. Ceftriaxone was superior to oral penicillin in a subgroup of patients with more than one symptom prior to therapy (p<0.01), but not in the overall evaluation of clinical, serological and bacteriological outcome data. Ceftriaxone ought to be preferred to oral penicillin in patients with more severe early Lyme borreliosis.
Journal Article•
TL;DR: A hybrid cefE gene was constructed by juxtaposing promoter sequences from the Penicillium chrysogenum pcbC gene to the open reading frame of the Streptomyces clavuligerus cefS gene, which codes for the enzyme penicillin N expandase.
Abstract: A hybrid cefE gene was constructed by juxtaposing promoter sequences from the Penicillium chrysogenum pcbC gene to the open reading frame of the Streptomyces clavuligerus cefE gene. In S. clavuligerus the cefE gene codes for the enzyme penicillin N expandase [also known as deacetoxycephalosporin C synthetase (DAOCS)]. To insert the hybrid cefE gene into P. chrysogenum the vector pPS65 was constructed; pPS65 contains the hybrid cefE gene and the Aspergillus nidulans amdS gene. The amdS gene encodes acetamidase and provides for dominant selection in P. chrysogenum. Protoplasts of P. chrysogenum were transformed with pPS65 and selected for the ability to grow on acetamide medium. Extracts of cells cultivated in penicillin production medium were analyzed for penicillin N expandase activity. Penicillin N expandase activity was detected in approximately one-third of the transformants tested. Transformants WG9-69C-01 and WG9-61L-03 had the highest specific activities of penicillin N expandase: 4.3% and 10.3%, respectively, relative to the amount of penicillin N expandase in S. clavuligerus. Untrasformed P. chrysogenum exhibited no penicillin N expandase activity. Analysis of the penicillin V titer revealed that WG9-61L-03 produced titers equal to that of the recipient strain while the amount of penicillin V produced in WG9-69C-01 was reduced by five fold.
TL;DR: Results indicate that the in vitro and in vivo activities of cefuroxime against B. burgdorferi are comparable to those of several oral antibiotics currently being used in the treatment of early Lyme disease and suggest that the oral form of this cephalosporin may be an effective alternative therapy for this disease.
Abstract: The in vitro and in vivo susceptibilities of the Lyme disease pathogen Borrelia burgdorferi to cefuroxime were compared with those of several other antibiotics commonly used to treat this disease. Cefuroxime demonstrated a higher MBC in vitro (1.0 microgram/ml) than ceftriaxone (0.08 microgram/ml) or erythromycin (0.32 microgram/ml), but the MBC was similar to that of amoxicillin (0.8 microgram/ml) and doxycycline (1.6 micrograms/ml). B. burgdorferi was considerably less susceptible to tetracycline (3.2 micrograms/ml) and penicillin G (6.4 micrograms/ml). Of the three other Borrelia species tested, two (Borrelia turicatae and Borrelia anserina) also demonstrated susceptibility to cefuroxime, while the third (Borrelia hermsii) was less susceptible. Results obtained with four antimicrobial agents in the in vivo hamster model parallel the antibiotic susceptibilities in the in vitro study. The three antibiotics with similar MBCs in vitro, i.e., cefuroxime, doxycycline, and amoxicillin, demonstrated comparable activities in preventing borreliosis in B. burgdorferi-challenged hamsters (50% curative doses = 28.6, 36.5 and 45.0 mg/kg, respectively). Penicillin G, which demonstrated the highest MBC in vitro, had very weak protective activity in the hamster model system. These results indicate that the in vitro and in vivo activities of cefuroxime against B. burgdorferi are comparable to those of several oral antibiotics currently being used in the treatment of early Lyme disease and suggest that the oral form of this cephalosporin may be an effective alternative therapy for this disease.
TL;DR: Third generation cephalosporins are far more effective onBorrelia burgdorferi spirochetes than penicillin G, as can be deduced fromin vitro susceptibility data.
Abstract: The low responsiveness of Lyme arthritis to high dose intravenous penicillin G therapy has evoked the demand for new drugs for the treatment of late stage borreliosis. As can be deduced from in vitro susceptibility data, third generation cephalosporins are far more effective on Borrelia burgdorferi spirochetes than penicillin G. The study presented here was designed to compare cefotaxime at a dosage of 2 x 3 g/day with penicillin G at a dosage of 2 x 10 megaunits/day, for ten days in a prospective randomized trial. A total of 135 patients were included in the study. They were diagnosed to suffer from late stage Lyme borreliosis on the basis of defined clinical symptoms compatible with stage three borreliosis manifestations of at least six months' duration and positive antibody titers against B. burgdorferi. Final outcomes were recorded after a 24 month post-treatment observation period with re-examination at three-month-intervals. Cefotaxime proved to be significantly superior to penicillin G with 87.9% versus 61.3% of treatments resulting in full or incomplete remission of symptoms (p = 0.002). Clinical remission was accompanied by declining antibody titers. Herxheimer-like reactions were observed in 20% of the patients of the penicillin group and in 40.5% of the patients of the cefotaxime group and may be interpreted as an indication of a response to therapy.
TL;DR: The in vitro susceptibilities of 10 isolates of Erysipelothrix rhusiopathiae to 16 antimicrobial agents were determined and penicillin and imipenem were the most active agents.
Abstract: The in vitro susceptibilities of 10 isolates of Erysipelothrix rhusiopathiae to 16 antimicrobial agents were determined. Penicillin and imipenem were the most active agents, followed by piperacillin, cefotaxime, ciprofloxacin, pefloxacin, and clindamycin. Some resistance was observed with erythromycin, tetracycline, and chloramphenicol. Activity was poor or absent with vancomycin, teicoplanin, daptomycin, trimethoprim-sulfamethoxazole, gentamicin, and netilmicin.
TL;DR: Eighty-nine Staphylococcus aureus strains were grouped according to their susceptibility or resistance to methicillin and oxacillin, and a penicillin-binding protein assay indicated that borderline methiillin-resistant S. aUREus strains do not produce PBP 2a.
Abstract: Eighty-nine Staphylococcus aureus strains were grouped according to their susceptibility or resistance to methicillin and oxacillin. The role of beta-lactamase in borderline methicillin resistance was confirmed by tests with beta-lactamase inhibitors, particularly when salt-supplemented medium was used. A penicillin-binding protein assay indicated that borderline methicillin-resistant S. aureus strains do not produce PBP 2a. Images
TL;DR: Given the high penicillin and ampicillin treatment failure rates when attempting to eradicate vaginal GBS colonization and the findings of higher and multiple drug resistance patterns of GBS, the selection of an alternative antibiotic regimen is of considerable clinical importance.
Abstract: This study examined the antibiotic resistance patterns of group B streptococci (GBS) isolated from gravid women. A total of 156 vaginal and cervical isolates of GBS were examined for resistance to penicillin, ampicillin, clindamycin, cefoxitin, gentamicin, and erythromicin. No resistance to penicillin or ampicillin was found, nor was penicillinase production demonstrated. A high level of resistance to gentamicin was noted (91%). Of the isolates examined, 9, 9.5, and 15.3% exhibited either resistance or intermediate susceptibility to erythromycin, clindamycin, and cefoxitin, respectively. Thirty strains (19%) exhibited a multiple antibiotic resistance pattern. Given the high penicillin and ampicillin treatment failure rates when attempting to eradicate vaginal GBS colonization and our findings of higher and multiple drug resistance patterns of GBS, the selection of an alternative antibiotic regimen is of considerable clinical importance. We recommend that routine reporting of GBS susceptibilities by clinical laboratories be adopted.
TL;DR: Clinical findings relating to 11 patients in Hong Kong and to 43 patients described elsewhere, all with Streptococcus zooepidemicus septicaemia, are reviewed and pigs were incriminated as a possible source of human infection.
TL;DR: The in vitro susceptibilities of 551 community isolates of Streptococcus pneumoniae from the Canadian province of Ontario to several new fluoroquinolones and beta-lactam antimicrobial agents were determined by a broth microdilution technique.
Abstract: The in vitro susceptibilities of 551 community isolates of Streptococcus pneumoniae from the Canadian province of Ontario to several new fluoroquinolones and beta-lactam antimicrobial agents were determined by a broth microdilution technique. Eight (1.5%) of these isolates were moderately susceptible (MICs, greater than or equal to 0.12 and less than or equal to 1.0 microgram/ml) to penicillin; none was resistant. Temafloxacin, ciprofloxacin, and ofloxacin (MICs for 90% of strains tested, between 1 and 2 micrograms/ml) were the most active fluoroquinolones tested, and BMY-28100 (MIC for 90% of strains tested, 0.25 microgram/ml) was the most active of the new beta-lactams tested.
TL;DR: IPV represents a practical and stable reagent for rapid PBP assays and use of IPV as the imaging agent in competition experiments for determination of the affinities of various beta-lactam antibiotics for the PBPs of E. coli yielded results similar to those obtained in experiments with [3H]penicillin G.
Abstract: Radiolabeled penicillin G is widely used as the imaging agent in penicillin-binding protein (PBP) assays. The disadvantages of most forms of labeled penicillin G are instability on storage and the long exposure times usually required for autoradiography or fluorography of electrophoretic gels. We investigated the utility of radioiodinated penicillin V as an alternative reagent. Radioiodination of p-(trimethylstannyl)penicillin V with [125I]Na, using a modification of the chloramine-T method, is simple, high yielding, and site specific. We demonstrated the general equivalence of commercially obtained [3H]penicillin G and locally synthesized [125I]penicillin V (IPV) in their recognition of bacterial PBPs. Profiles of PBPs in membranes from Bacteroides fragilis, Escherichia coli, Providencia rettgeri, Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis, and Enterococcus faecium labeled with IPV or [3H]penicillin G were virtually identical. Use of IPV as the imaging agent in competition experiments for determination of the affinities of various beta-lactam antibiotics for the PBPs of E. coli yielded results similar to those obtained in experiments with [3H]penicillin G. Dried electrophoretic gels from typical PBP experiments, using IPV at 37.3 Ci/mmol and 30 micrograms/ml, exposed X-ray film in 8 to 24 h. The stability of IPV on storage at 4 degrees C was inversely proportional to specific activity. At 37.3 Ci/mmol and 60 micrograms/ml, IPV retained useful activity for at least 60 days at 4 degrees C. IPV represents a practical and stable reagent for rapid PBP assays. Images
TL;DR: It is concluded that S aureus is the most common cause of impetigo in children in the study population, that cephalexin is themost effective treatment, that erythromycin estolate is nearly equally effective and may be preferred on a cost-effectiveness basis, and that penicillin V is inadequate for treatment of this infection.
Abstract: • We attempted to determine the causative bacterial pathogens of impetigo in children in our area, to compare the effectiveness of three frequently used oral antimicrobial treatment regimens, and to correlate the antimicrobial sensitivity of the bacterial isolates with clinical responses to treatment. Seventy-three children with impetigo were randomly assigned to receive penicillin V potassium or cephalexin monohydrate, both administered in dosages of 40 to 50 mg/kg per day, or erythromycin estolate administered in a dosage of 30 to 40 mg/kg per day. All drugs were given in three divided doses for 10 days. Treatment failure was defined as persistence of lesions 8 to 10 days after initiation of drug therapy as determined by examiners blinded to the treatment therapies. Forty-five (62%) cultures showed Staphylococcus aureus only, 14 (19%) showed S aureus and group A β-hemolytic streptococci, six (8%) showed group A β-hemolytic streptococci only, and eight (11%) showed no growth or other organisms. Treatment failure occurred in six (24%) of 25 patients treated with penicillin V, one (4%) of 25 patients treated with erythromycin estolate, and no patients treated with cephalexin. We conclude that S aureus is the most common cause of impetigo in children in our study population, that cephalexin is the most effective treatment, that erythromycin estolate is nearly equally effective and may be preferred on a cost-effectiveness basis, and that penicillin V is inadequate for treatment of this infection. ( AJDC . 1990;144:1313-1315)
TL;DR: It is shown that a short course of five days treatment with cefpodoxime is as effective as the ten days of conventional treatment with penicillin in terms of both clinical and bacteriological efficacy.
Abstract: A ten day course of oral penicillin is still recommended for pharyngotonsillitis with the aim of eradicating Streptococcus pyogenes and preventing rheumatic fever. However there is some evidence that penicillin V therapy is less satisfactory than in former years. Several explanations have been suggested, including inadequate pharmacokinetic properties, poor patient compliance, penicillin tolerance, re-infection and carrier state, and indirect pathogenicity. In this context we evaluated the efficacy of third generation cephalosporins. We have shown that a short course of five days treatment with cefpodoxime is as effective as the ten days of conventional treatment with penicillin in terms of both clinical and bacteriological efficacy. Moreover the possibility of reducing the duration of therapy and the twice daily administration of these new cephalosporins results in better patient compliance with treatment.