Showing papers on "Penicillin published in 1971"

Studies on antibiotic synergism against enterococci: II. Effect of various antibiotics on the uptake of 14C-labeled streptomycin by enterococci

Abstract: The mechanism by which agents that inhibit bacterial cell wall synthesis produce a synergistic effect against enterococci when combined with aminoglycoside antibiotics has not been elucidated. Using 14C-labeled streptomycin, it could be shown that uptake of this aminoglycoside antibiotic was markedly enhanced in enterococci growing in the presence of penicillin or other agents which inhibit the synthesis of bacterial cell walls. There was no enhancement of streptomycin uptake when the cells were incubated with antibiotics which primarily affect the bacterial cell membrane or inhibit protein synthesis. Increased streptomycin uptake was produced by penicillin only in actively growing bacteria. These observations are consistent with the hypothesis that enterococci exhibit a natural barrier to the entry of streptomycin which can be overcome by agents which inhibit cell wall synthesis, thus producing a synergistic effect.

Increased Resistance to Penicillin of Pneumococci Isolated from Man

Abstract: Strains of Diplococcus pneumoniae relatively insensitive to penicillin were isolated from an aboriginal child in Australia and from 15 New Guineans. The concentration of penicillin required to inhibit growth was 25 times that which inhibited sensitive pneumococci. These pneumococci were also partially resistant to cephalosporin antibiotics. All the relatively insensitive pneumococci from New Guinea were identified as Type 4, suggesting that transmission of the partially resistant strain had occurred. The isolations were made from persons who lived in remote areas where penicillin had frequently been used.

Meningitis due to Listeria monocytogenes. A review of 25 cases.

Abstract: Twenty-five patients with bacteriologically proved Listeria monocytogenes meningitis were studied. Twenty-one were male. Nine of the 25 were neonates, and 11 were 55 years of age or older. Twenty-four patients received either ampicillin or penicillin, at times in combination with other antibiotics. One of the ampicillin-treated patients, and six of the penicillin-treated patients died. Recovery of the patient from meningeal infection seemed to correlate best with an initial cerebrospinal-fluid glucose level over 30 mg per 100 ml. These data, like those already appearing in the literature, suggest that intravenous ampicillin may be the therapy of choice, from the standpoint of both superior efficacy and relative lack of toxicity.

Synergy of Penicillin and Gentamicin against Enterococci

Abstract: Because combinations of penicillin plus streptomycin and penicillin plus kanamycin do not produce synergism against all strains of enterococci, the effect of penicillin plus gentamicin against enterococci was examined. A very high level of resistance to gentamicin was absent in 172 strains of enterococci isolated from clinical specimens. Penicillin plus gentamicin was synergistic against all of 30 strains tested. The size of the inoculum had a significant effect when low concentrations of gentamicin were tested against certain of the strains. Nonetheless, the combination of penicillin plus gentamicin produced enhanced killing of all enterococci tested when used in clinically achievable concentrations.

Antibiotic Concentrations in Septic Joint Effusions

Abstract: Fifty specimens from 27 infants and children with septic joint disease were assayed for ampicillin (18 specimens), methicillin (14 specimens), penicillin (14 specimens) or cephalothin (four specimens). The ranges of observed values varied depending upon the dose and the interval after administration. The joint-fluid level was the same as or higher than the serum level in eight of nine paired specimens tested for ampicillin and in seven of 11 paired specimens assayed for methicillin. Comparable serum and joint-fluid levels of penicillin were found in 11 of 12 paired specimens. The four antibiotics studied enter joint fluid in concentrations greatly in excess of in vitro inhibitory levels of the usual bacteria that cause septic arthritis. There is no need for intra-articular administration. Intramuscular therapy appears as effective as the intravenous route with ampicillin and probably with methicillin and penicillin.

Routine Use of Penicillin Skin Testing on an Inpatient Service

Abstract: The routine use of prospective penicillin skin testing on hospitalized patients was evaluated over a six-month period. Patients with clinical indications for the use of penicillin drugs were tested with penicilloyl-poly-L-lysine (PPL) and a mixture of minor penicillin antigens (MDM), regardless of past history of penicillin reactions. Fifty-four patients with reasonable histories of penicillin hypersensitivity but nonreactive skin tests were treated, with only one mild possible reaction occurring within the first three days of therapy; this patient had active systemic lupus erythematosus. Ten of 163 patients without histories of prior penicillin reactions had positive skin tests and were denied penicillin drugs. As compared to a similar study of the same inpatient population in 1964–65, penicillin reactions were markedly less frequent. The routine use of PPL and MDM skin tests by house officers on a busy ward service is practical, safe and useful in predicting penicillin reactions.

Penicillin Combined with Gentamicin or Streptomycin: Synergism against Enterococci

Abstract: The action of penicillin in combination with gentamicin against enterococci was studied. One hundred strains of enterococci, 14 of which were recovered from blood cultures of patients with endocarditis, were studied for susceptibility to penicillin, gentamicin, and streptomycin. All strains were inhibited by ^50 ^g of gentamicin/ml. The majority were inhibited by ^78 pg of streptomycin/ml, but 13 strains were not inhibited by 50,000 pg/ml. Thirty-three strains were studied for synergism of combinations of antibiotics. A combination of 20 pg of penicillin and 4 pg of gentamicin/ml was synergistic against all 33 strains, while 20 pg of penicillin combined with 20 pg of streptomycin/ml was synergistic against only 20 of the 33 strains. The minimal inhibitory concentration of streptomycin for four of these 20 strains was more than 50,000 pg/ml. The combination of penicillin and gentamicin may be considered an alternative for the treatment of enterococcal endocarditis, especially when penicillin and streptomycin are not synergistic.

Mechanism of Resistance to Antibiotic Synergism in Enterococci

Abstract: Enterococci exhibit two types of resistance to streptomycin. Moderately high-level resistance is observed in most naturally occurring strains and can be overcome by simultaneous exposure to penicillin. In addition, very high-level resistance is found in those strains against which penicillin plus streptomycin fail to produce synergism in vitro. To study the mechanism of streptomycin resistance in enterococci, ribosomes from a wild-type strain and from a highly streptomycin-resistant mutant were isolated, characterized, and studied in an in vitro amino acid incorporation system. The ribosomes from the organism with moderately high-level streptomycin resistance were sensitive to streptomycin in vitro, suggesting that this type of resistance is caused by failure of streptomycin to reach the ribosomes. Very high-level resistance (and lack of penicillin-streptomycin synergism), on the other hand, appears to be due to ribosomally mediated streptomycin resistance.

Detection of penicillin allergy of the immediate type by radioimmunoassay of reagins (IgE) to penicilloyl conjugates.

Abstract: Summary Reaginic antibodies (IgE) to penicilloyl were detected by an in vitro method, a radioimmunological technique (RAST), in the sera of nine patients out of eleven with a recent history of penicillin hypersensitivity of the immediate type. Provocation tests in two patients with negative RAST were negative as well as in twelve patients having had a possible penicillin hypersensitivity reaction 7 months to 14 years ago. Results from skin tests and RAST agreed. Skin tests and RAST reactions were negative for thirty-two patients with a history of penicillin reactions of the delayed type. The results of this study indicate that the RAST is a valuable alternative to the more dangerous intracutaneous test with penicilloyl-polylysine for-detection of penicillin hypersensitivity of the immediate type.

Prevention of Bacterial Overgrowth

Abstract: For years it has been recognized that one of the hazards of the use of antibiotics is gross alteration in the normal pattern of bacterial flora. Secondary to this is overgrowth with organisms not commonly found in significant proportions at the study site [1-4]. Such overgrowth may be followed by superinfection, a complication with a high mortality rate [4]. In an earlier report [5], we discussed the importance of interrelationships among bacterial species in maintaining the status quo of bacterial flora in the oropharynx. Data were presented which suggest that members of the viridans group of streptococci, the predominant strains of the oropharyngeal flora in most individuals, can inhibit the growth of enteric gram-negative bacilli, the organisms that commonly overgrow at this site following therapy with massive doses of penicillin. It was proposed that suppression (or elimination) of these streptococci by massive doses of antibiotics suppresses (or eliminates) their inhibitory action and permits multiplication of the previously inhibited (or newly introduced) bacilli. During parenteral therapy with large doses of penicillin, individuals carrying streptococci that were resistant to the levels attained in the pharynx * and that persisted, therefore, while the antibiotic was being given, did not demonstrate overgrowth [5]. In retrospect, such patients had recently received penicillin orally. Such exposure to the antibiotic is known to favor the selection of resistant

Bacterial Persistence in Streptococcal Endocarditis Due to Thiol-Requiring Mutants

Abstract: Defective strains of Streptococcus were isolated from cardiac valves or blood cultures from three patients with bacterial endocarditis. These strains did not grow on the usual media under aerobic or anaerobic conditions. Enrichment of media with L-cysteine, reduced glutathione, thioglycollic acid, or dithiothreitol was required for growth. Deficient mutants with the same requirements for thiol groups were selected in vitro from streptococci of Group N by a two-step procedure. In an experimental model in mice, the combination of penicillin and streptomycin did not act synergistically against these deficient streptococci as it did against normal strains. The physiologic properties of the defective streptococci make it difficult to isolate them from clinical specimens and to diagnose and treat infections in which they are the causative organism.

Report of the Penicillin Study Group—American Academy of Allergy

Abstract: Many aspects of the problem of penicillin hypersensitivity remain unsolved. The Penicillin Study Group of the American Academy of Allergy was formed to investigate various aspects of this problem. A number of studies have attempted to evaluate the relationship of clinical penicillin hypersensitivity to reactions to skin tests with penicillin and its degradation products. These studies generally have shown positive correlations, but considerable variation has existed in their magnitude.= This variation may well relate to differences in protocol, techniques, patient populations, or investigators.2-n The present cooperative study was devised to investigate the relationship of skin reactivity to penicillin hypersensitivity. The reagents used were penicillin G (Pen G) and penicilloyl-polylysine (PPL), a conjugated form of a penicillin degradation product (penicilloyl) , which prior studies have shown to be associated with the majority of penicillin hypersensitivity reactions.g The patient population was drawn from the clinical and private practices of practicing allergists who are members of the Penicillin Study Group of the American Academy of Allergy.

Neurotoxicity of Intravenously Administered Penicillin G

Abstract: Penicillin G, 20 million units daily given intravenously to a nonuremic patient, caused encephalopathy (progressive restlessness, confusion, hallucinations, and multifocal myoclonus) followed by recovery after discontinuation of the drug. In normal awake cats doses up to 1.3 million units/ kg produced encephalopathy with myoclonus; higher doses culminated in status epilepticus and death. Pretreatment with small doses minimized the effects of a subsequent high dose. In awake rats 4.5 to 5 million units/kg produced encephalopathy resulting in death of the majority of animals. In rats anesthetized with ether, same results were obtained with 3 to 3.5 million units/kg. The highest concentrations of labeled penicillin G in brain, located mostly in membranal-nuclear fraction, was reached in five to ten minutes. The penicillin encephalopathy was reversed in animals by intravenously administered penicillinase.

Penicillinase and the convulsant action of penicillin.

Abstract: PENICILLIN HAS BEEN RECOGNIZED as a convulsant agent since Walker and Johnson1 discovered that it produces epileptiform activity when applied to the cerebral cortex of cats, dogs, monkeys, and human beings. Borkowsky and Forster‘ subsequently reported that highvoltage spike discharges in the EEG and simultaneous clonic jerks in appropriate limb muscles were produced by cortical penicillin application. Experimentally, the topical application of penicillin to neocortex3-s and to archicortex6 has been a useful technique for studying the basic mechanisms of acute focal epileptogenesis. Recently it has been shown that the administration of large doses of parenteral Na penicillin G to intact cats produces a convulsive state which is electrographically and behaviorally similar to “centrencephalic” epilepsy in man.? The convulsant nature of penicillin has also been of clinical importance. In the treatment of pneumococcal meningitis, an intrathecal dose of penicillin greater than 1OO,OOO units in the adults or 10,000 units in the childJ induces seizures. Convulsions may follow the administration of large doses of pa ren ted penicillin to patients with azotemia’OJ1 or with overwhelming infections’? and to patients during cardiopulmonary bypass procedures.13 In reproducing this clinical condition in dogs, Wyant and Dobell14 found that it was necessary to induce an air embolus at the time of penicillin infusion in order to produce seizures. Presumably, this procedure insured a breakdown in the integrity of the blood-brain barrier. The bacterial enzyme penicillinase catalyzes the hydrolysis of the lactam ring of penicillin to produce penicilloic acid and thus destroys the antimicrobial and antigenic properties of the antibiotic.lZ This reaction occurs in vitro, where it is used in bacteriological procedures, and also in vivo, where it is used to effectively inactivate circulating penicillin. In view of the possible implications for the clinical use of this enzyme in cases of penicillin-induced encephalopathy, and in order to further our understanding of the convulsive action of penicillin, we studied the effects of penicillinase on the epileptogenic properties of penicillin.

Differing patterns of wheal and flare skin reactivity in patients allergic to the penicillins

Abstract: We compared the immediate wheal and flare skin test reactivity to major and minor antigenic determinants from penicillin G, ampicillin, and methicillin in 240 patients. In 57 patients with positive skin tests to one or another of these drugs, a marked variability in the patterns of reactivity was noted. Among the major determinants, 24 patients reacted to only one drug, 5 to all three drugs, and 8 to two of the drugs. Among the minor determinants, 20 patients reacted to only one drug, 5 to all three drugs, and 9 reacted to two drugs. These results show that a positive skin test to one penicillin drug is not necessarily associated with positive reactions to all the penicillin drugs, indicating that skin test reagents to semisynthetic penicillins as well as to penicillin G may be useful.

Studies on the Immune Response to Penicillin and Cephalothin in Humans I. Optimal Conditions for Titration of Hemagglutinating Penicillin and Cephalothin Antibodies

Abstract: This study evaluated the critical factors in the titration of penicillin and cephalosporin antibodies using hemagglutination techniques. Emphasis was placed on the development of sensitive and reproducible methods for further investigational work as well as the development of a simple and practical method suitable for use by clinical laboratories with only occasional need for performing such tests. Conditions for optimal sensitization of erythrocytes with the antibiotics were evaluated including concentration of the antibiotics; pH, temperature, and time of sensitization; comparison of red cells from different donors; and the effects of varying conditions of storage and age of the red cells. Optimal sensitization of red cells by penicillin are obtained when 1 ml of fresh erythrocytes is incubated with 1,000,000 units Kbenzylpenicillin G in 15 ml Trimethylamine (TMA)-buffer, pH 10.0, at room temperature for 2 hr. Similarly, for preparation of cephalothin-sensitized red cells, 1 ml of fresh erythrocytes is incubated with 400 mg Na-cephalothin in 10 ml TMA-buffered saline (pH 10.0) at 37°C for 2 hr. Red cells sensitized at pH 10.0 with penicillin gave titers 30 times higher than those sensitized at pH 7.3, but only marginal differences were noted with cephalothin. Several hemagglutination systems were evaluated, including standard blood-banking methods such as saline, albumin and antiglobulin techniques. These were compared with agglutination in a diluent containing dextran, normal rabbit serum, and Tris-buffered saline (Dex-NRS-TBS). The indirect antiglobulin (Coombs') test using antibiotic-sensitized cells is optimal for clinical purposes. However, if numerous penicillin and cephalothin antibody titrations are to be performed for investigational work, direct agglutination in Dex-NRS-TBS is generally more practical.

In Vitro Studies of α-Carboxyl-3-Thienylmethyl Penicillin, a New Semisynthetic Penicillin

Abstract: The activity of a new semisynthetic penicillin, α-carboxyl-3-thienylmethyl penicillin (BRL-2288) was determined against 535 clinical isolates of gram-negative bacilli, by using the tube dilution technique Nearly 80% of isolates of Proteus spp were inhibited by 312 μg or less of this antibiotic per ml BRL-2288 was as active as ampicillin against Escherichia coli It was slightly more active than carbenicillin or 6-(d-α-sulfoaminophenylacetamido)-penicillanic acid against Pseudomonas sp, with over half of the isolates being inhibited by 50 μg or less of BRL-2288 per ml Isolates of Klebsiella sp were routinely resistant to this antibiotic The drug was bactericidal against most sensitive organisms BRL-2288 was less active against large inocula A strain of Pseudomonas sp which developed resistance to carbenicillin also developed resistance to BRL-2288 simultaneously

Detection in vitro of cellular hypersensitivity to drugs

Abstract: The in vitro macrophage migration inhibition technique was used to detect the presence of cellular hypersensitivity in patients with suspected drug allergies. Blood lymphocytes from 11 patients (3 serum sickness, 1 allergic vasculitis, 2 nitrofuradantoin syndrome, 1 erythema nodosum, 2 erythema multiforme, 1 polymyalgia rheumatica, 1 granulomatous hepatitis) and 10 control subjects were assayed for the in vitro production of migration inhibitory factor (MIF) in response to penicillin G, sulfisoxazole, and nitrofuradantoin. Lymphocytes from 6 of 11 patients with clinical manifestations of drug hypersensitivity produced MIF in response to the suspected drug but not in response to other drugs. The serum from one patient with serum sickness secondary to penicillin allergy stimulated autologous lymphocytes as well as those of control subjects to incorporate increased amounts of 3 H-thymidine, a finding that could be explained by the presence of immune complexes in the patient's serum. Lymphocytes from the control subjects did not produce MIF in response to any of the drugs, suggesting that this technique may be of use in the detection of drug allergies.

Pneumococci insensitive to penicillin.

Abstract: PNEUMOCOCCI of all capsular types have been regarded as highly sensitive to penicillin1 since its introduction for the treatment of human infections in 1940. Although penicillin-insensitive mutants can be selected in vitro by repeated subculture in the presence of sub-inhibitory concentrations of penicillin2–6, resistant wild strains were not recognized until 1967, when penicillin-insensitive pneumococci (type 23) were isolated from a patient with hypogammaglobulinaemia and bronchiectasis, who had received much antibiotic therapy, including penicillin7. We now report further strains of pneumococci, isolated in Australia and New Guinea, relatively insensitive to both penicillin and cephalosporin antibiotics.

Microbial transformations of antibiotics.

Abstract: Publisher Summary This chapter the microbial transformations of antibiotics. Although years have passed since the first reports of the therapeutic promise of penicillin, and the description of a microbial transformation of this antibiotic, only a little effort has been invested in using enzymes to produce new and potentially useful antibiotic derivatives. The signal success of the programs on chemical modification of a number of antibiotics—including penicillin, cephalosporin, tetracycline, lincomycin, and rifamycin—has encouraged large-scale efforts in preparing modifications of other antibiotics by chemical means. Many antibiotics have been shown to be susceptible to microbial attack. A measure of success has been noted only in the hydrolysis of benzylpenicillin to 6-aminopenicillanic acid, and of mannosidostreptomycin to the clinically more interesting streptomycin. Many other antibiotics have been modified (and thereby inactivated) or degraded by microbial enzymes, but no practical application has been found for most of the products.

Treatment of Group A Streptococcal Pharyngitis in Children: Comparison of Lincomycin and Penicillin G Given Orally and Benzathine Penicillin G Given Intramuscularly

Abstract: Two hundred twenty-eight children with group A β-streptococcal pharyngitis, or carrier state, were treated with one of three treatment regimes from September 1969 to March 1970 and followed-up with throat cultures at 5, 14, 31, and 60 days. Treatment groups were benzathine penicillin G given intramuscularly, and penicillin G potassium and lincomycin hydrochloride monohydrate, administered orally. Lincomycin hydrochloride monohydrate given orally in recommended dosages for ten days was found to be as effective as benzathine penicillin G given intramuscularly (cure rates at 31 days, 86.8% and 88.9%, respectively). Both drugs were more effective than penicillin G given orally for ten days (31-day cure rate, 70%). The 60-day cure rates were 84% for lincomycin given orally, 72% for benzathine penicillin G given intramuscularly, and 60% for penicillin G given orally.

Experimental infection of the skin in the hamster simulating human impetigo ii. assessment of various therapeutic regimens

Abstract: The efficacy of various therapeutic regimens for the treatment of impetigo was assessed in an experimental animal model. The topical application of gentamicin or bacitracin and removal of scabs were ineffectual. PHisoHex scrubbing delayed healing significantly and resulted in the development of satellite lesions. Healing was significantly promoted by the administration of penicillin, the benzathine variety being more effective than procaine penicillin. Benzathine penicillin was similarly effective in pure streptococcal lesions and in mixed lesions containing penicillin-sensitive or penicillin-resistant staphylococci in addition to streptococci. The development of skin lesions was markedly reduced following prophylactic administration of benzathine penicillin.

Intrarenal distribution of penicillin, cephalothin, ampicillin and oxytetracycline during varied states of hydration

Abstract: After the constant infusion of an antibiotic, tissue concentrations of the drug measured within the cortex, medulla and papilla of the dog kidney show considerable variation depending upon the type of antibiotic and the state of hydration of the experimental animal. In the hydropenic state, a significant gradient of increasing concentration from cortex to papilla occurs with penicillin and cephalothin, whereas ampicillin and oxytetracycline concentrations do not differ between cortex, medulla and papilla. The increase in antibiotic concentration from cortex to papilla was 4-fold for penicillin and 3-fold for cephalothin. Hydration effectively dissipated these gradients. The increase in tissue gradients during hydropenia may be attributed in part to high antibiotic concentrations in medullary and papillary intratubular urine. However, it appears that the papillary tissue water concentration for some of the antibiotics may be significantly increased over concomitant serum levels. Papillary tissue water concentration of penicillin exhibited a 10-fold, cephalothin a 6½-fold and oxytetracycline a 2½-fold increase over simultaneously existing serum levels during hydropenia. This form of investigation provides a means for selecting antibiotics most effectively concentrated in the papillary and medullary tissues and yields information of potential therapeutic importance.