Large Doses Of Penicillin Research Articles

Effect of penicillin and chloramphenicol on the growth and endotoxin release by N. meningitidis

The action of two antibiotics, penicillin and chloramphenicol, on bacterial growth and endotoxin liberation was studied in 18 strains of Neissevia meningitidis isolated from blood and CSF of patients with meningococcal infections. The antibiotics were administered both separately and in combined form in doses equivalent to 1 MIC and 100 MIC. Penicillin was found to produce a faster and more intense bactericidal effect than chloramphenicol during the first hour, whereas at 12 h these differences were not significant. This could explain the initial worsening observed in some infected patients when large doses of penicillin are administered. An increased liberation of endotoxin after adding penicillin was observed in six of the strains studied, whereas the remaining 12 did not show significant increases. The six strains (belonging to serogroup B) were known to have an enhanced capacity for spontaneous endotoxin liberation.

Role of catecholaminergic mechanisms and the caudate nucleus in the development of generalized convulsions caused by parenteral injection of penicillin

The behavioral and EEG changes induced by a single intramuscular injection of large doses of penicillin were recorded in unrestrained cats. The eyes closed tightly and myoclonic spasms appeared, accompanied by slow negative waves and spike-wave complexes in the cortex and caudate nucleus. Stimulators of catecholaminergic transmission (L-dopa and apomorphine) interfered with the development of these phenomena but facilitated the triggering of tonicoclonic convulsions. Inhibitors of catecholaminergic transmission (chlorpromazine and haloperidol) has the opposite effect. Electrolytic injury to the head of the caudate nucleus also interfered with the formation of phenomena similar to a minor epileptic fit, whereas threshold lowfrequency stimulation of the nucleus, on the other hand, potentiated the effect of penicillin.

Listeria Encephalitis in Five Renal Transplant Recipients

Listeria encephalitis has occurred recently in 5 renal transplant recipients at the Transplantation Unit in Stockholm. Symptoms from the central nervous system, such as coma, hemiparesis and cranial nerve paresis, dominated the clinical picture. Listeria monocytogenes was isolated from the blood of all the patients, from the cerebrospinal fluid in two, from the urine in one and post mortem from the brain in one patient. Pleocytosis never exceeded 200 leucocytes/mm3 and the glucose ratio was normal or near normal. Complement fixation test for Listeria was negative in all 5 patients. Four patients expired in spite of treatment with large doses of penicillin and other antibiotics to which the isolated strains were sensitive in vitro. At autopsy, inflammation and necrosis were observed in the brain, especially the brain stem, and there was mild lymphocytic infiltration of the meninges. The surviving patient was treated with a combination of chloramphenicol and ampicillin.

Erysipelas and necrotizing fasciitis

The clinical course of necrotizing fasciitis in 8 patients is compared with observations on 22 other patients with erysipelas. In necrotizing fasciitis the early erythematous areas turn into a dusky blue colour with later vesiculation and formation of bullae. An important finding is a non-pitting oedema extending outside the erythematous patches. The disease often progresses and involves further skin areas proximal to the initial ones. Gangrene tends to follow in multiple sites after the 1st week of illness. Group A streptococci in conjunction with widespread thrombosis and vascular necrosis of the involved skin are two major factors in the pathogenesis of the gangrene. Early debridement and excision of necrotic tissue in combination with large doses of penicillin and cloxacillin are confirmed as mandatory to remove toxaemia and inhibit further necrosis of the skin. In 3 of the 8 patients with necrotizing fasciitis the syndrome of disseminated intravascular coagulation complicated the course of the disease. A promising therapeutic result was seen in 2 further patients exhibiting alarming signs and symptoms of early necrotizing fasciitis; the combination of heparin, given intravenously in therapeutic doses guided by activated partial thromboplastin time studies, and of systemic antibiotics alleviated the symptoms, which vanished within 10 days of the start of treatment.

Pneumococcal Meningitis: A Clinical and Laboratory Study

Forty-two patients who were admitted consecutively with pneumococcal meningitis during an 18-month period were studied in Ahmadu Bello University Hospital, Zaria, Nigeria. The disease was seen most frequently in older children and young adults. A predisposing condition was found in only four patients. Counter-current immunoelectrophoresis was found to be a rapid and effective method of diagnosis: pneumococcal polysaccharide antigen was found in the initial cerebrospinal fluid (CSF) sample from all but one of the patients. Detailed physiological studies carried out in two patients showed profound disturbances of cerebral carbohydrate metabolism and an increase in cerebral vascular resistance. Twenty patients died (48 per cent) in spite of treatment with large doses of penicillin. A fatal outcome was associated with impairment of consciousness on admission, a low CSF white cell count and a high CSF antigen titre. It is suggested that marked changes in cerebral carbohydrate metabolism, and perhaps vascular damage, play important roles in producing severe brain damage in patients with pneumococcal meningitis and that defective CSF polymorphoneutrophil leukocyte function may contribute to the failure of the infection to respond satisfactorily to antibiotic therapy.

Prevention of bacterial overgrowth.

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

Effects of very large doses of penicillin G given orally to rats.

Nimni and Bavetta1 reported a connective tissue disorder in rats fed penicillamine. The disorder was reflected by decreased breaking strength of unwounded and wounded skin, decreased collagen synthesis in polyvinyl sponge implants and a diminished proportion of insoluble to soluble collagen in such granulomas. We have studied this phenomenon in rats and guinea-pigs2–4 and have likened it to the lathyritic state induced by feeding β-amino propionitrile, a view also expressed by Nimni5. Penicillamine can be derived6 from both the in vitro and the in vivo hydrolysis of penicillin, so we set out to determine whether the feeding of very large doses of penicillin would cause a collagen defect similar to that caused by penicillamine.

Treatment of Acute Nonspecific Primary Lung Abscess

ALTHOUGH the infectious etiology of acute nonspecific primary lung abscess has not been established, it has been the general experience that most of the cases respond to penicillin G. The treatment in wide usage requires frequent injections for many weeks. The optimal regimen with regard to dosage, route of administration, and duration of therapy has not been determined. Since the parenteral method is inconvenient to nursing personnel and annoying to patients, orally administered penicillin is worth consideration. The present study was undertaken to investigate the efficacy of treating acute nonspecific primary pulmonary suppuration with large doses of penicillin G by mouth. In the past, the authors have treated acute lung abscess successfully with aqueous penicillin G in a dosage of 300,000 units intramuscularly every six hours. On the basis of pharmacologic studies1 an oral dosage of four times the intramuscular amount was considered likely to be effective. The regimen used

AN EXPERIMENTAL STUDY OF PENICILLIN ANAPHYLAXIS

SUMMARY Intravenous injection of dialyzed penicillin-treated homologous serum produces anaphylaxis in guinea pigs sensitized either actively by a previous injection of this preparation, or passively by serum from a rabbit which had received injections of penicillin in Freund's Complete Adjuvant. In both cases, the intravenous administration of large doses of penicillin produces no adverse effect, but inhibits anaphylaxis on later challenge with penicillin-treated serum.

ANEMIA SECONDARY TO PENICILLIN TREATMENT: STUDIES ON TWO PATIENTS WITH "NON-ALLERGIC" SERUM HEMAGGLUTININS.

Abstract In two patients being treated with large doses of penicillin, progressive anemia developed which was severe enough to require several transfusions. Reticulocytosis and a positive direct Coombs antiglobulin reaction appeared during therapy. The sera of both patients contained antibodies which agglutinated penicillin-"sensitized" human erythrocytes in vitro. Neither patient was clinically allergic to penicillin. In hemagglutinin. inhibition studies, their sera showed little affinity for penicillin and the more antigenic hapten, penicilloyl ϵ-aminocaproate, in marked contrast to comparable studies on hemagglutinin from patients allergic to penicillin. It is possible that the agglutinins in these two patients were specific for an erythrocyte antigen which was exposed or produced by the action of penicillin in vivo and in vitro.

OBSERVATIONS ON AN UNKNOWN ORGANISM RECOVERED FROM RECURRENT ORAL LESIONS IN MAN

This paper describes an investigation into the aetiology of a variety of recurrent oral lesions in the adult, with the result that an unidentified organism was repeatedly demonslrated in sections of chorioallantoic membranes (CAMs) inoculated with 17 specimens of curetted tissues from recurrent oral lesions. The organism is a strict parasite which grows well in the CAMs of the developing hen"s egg, where it is seen to undergo growth phases of a complex nature. In the intracellular phases it may be mistaken for a virus or a rickettsia, in the extracellular phases for a bacterium or a protozoan. Pox are produced on the CAMs and haemorrhages and death occur in the embryos during the intracellular phases. The virulence of the organism increases with serial passage, with the production of a haemolytic toxin and 100% mortality rate. In tissue cultures the medium was rapidly metabolized and cytopathogenic effects occurred. Hanging drop preparations showed motility of a rapid, spinning, tumbling nature. The organism will not grow on a variety of enriched acellular media under aerobic or anaerobic conditions. It stains well with Giemsa"s stain but poorly with Gram"s. It is insensitive to large doses of penicillin and streptomycin. Guinea pigs and rabbits may be infected with the fresh primary material. CAM antigens do not fix complement in the presence of homologous serum or herpes simplex antisera. We have not been able to identify the organisms.

Penicillin N therapy of enteric bacillary infections.

Since the introduction of antibacterial agents, serious infections due to enteric pathogens have occurred with increasing frequency. 1 Because these microorganisms are quite often resistant to the commonly employed, safe antibacterial agents, therapy frequently requires the use of agents with significant potential for serious human toxicity. Specifically, the treatment of infections due to Salmonella species other than Salmonella typhosa are frequently not cured with chloramphenicol 2 ; Proteus mirabilis is resistant to the clinically usable concentrations of most antibiotics with the exception that large doses of penicillin G may be effective in some circumstances. 3 Recently, Noall et al 4 emphasized the difficulty in attaining success in treatment of Proteus infections. Approximately ten years ago the antibiotic penicillin N (cephalosporin N) was isolated and identified as D-4-amino-4-carboxy-n-butyl penicillin. When compared with penicillin G (benzyl penicillin), this penicillin was not very active as an inhibitor of Gram-positive microorganisms. However, it was surprisingly

Continuous intramuscular-drip penicillin therapy in bacterial endocarditis: A reaffirmation ∗

The effectiveness and ease of penicillin administration by continuous intramuscular drip has been re-emphasized. Its wider use is suggested in the treatment of those diseases in which large doses of penicillin are required.

Crystalline pancreatic desoxyribonuclease as an adjunct to the treatment of pneumococcal meningitis.

ALTHOUGH the pneumococcus is sensitive to many antibiotics, the mortality from pneumococcal meningitis has remained extraordinarily high. Mortality figures on more than 800 cases, in patients of all ages from 14 clinics, ranged from 8 per cent to 68 per cent and averaged 28 per cent.1 2 3 4 5 6 7 8 9 10 11 12 13 14 All these cases were adequately treated intravenously and intramuscularly with large doses of penicillin, together with sulfonamides. This high mortality has been attributed, in the acute phase, to cerebral edema with brain-stem compression, pressure from the inflammatory exudate (generalized, or due to cerebrospinal block) and systemic effects of the septicemia. During the subacute phase . . .

The effect of penicillin on acute rheumatic fever and valvular heart disease.

THE control of symptoms of acute rheumatic fever is easily attained by several methods of therapy, but no form of treatment has had a marked effect on acute carditis and valvular heart disease, the two complications that determine the ultimate prognosis. Since the initiating event of the acute rheumatic episode is infection by the Group A streptococcus, it appeared logical to attempt to alter the course of established rheumatic fever by removing the original inciting agent. To accomplish this objective, 49 patients with acute rheumatic fever received large doses of penicillin, and 48 patients received no antibiotic and served as . . .

CURRENT THERAPY: The Selection of an Antibiotic for the Treatment of Bacterial Endocarditis

Prior to the advent of potent bacteriostatic and bacteriocidal agents, it was common practice to subdivide cases of bacterial endocarditis into two groups: acvte bacterial endocarditis, i.e. bacterial endocarditis of less than the three or four weeks’ duration, and subacute bacterial endocarditis, which persisted for more than four weeks. The discovery and utilization of present-day antibiotics have changed the entire picture and course of bacterial invasion of the endocardium and made the distinction meaningless. Preferably, in classification emphasis should be placed on the specific organism responsible for the bacterial invasion and, where known, the name of the organism should be made a part of the disease designation. Some bacteria prove relatively resistant to penicillin; others actually produce a specific penicillin-destroying enzyme known as penicillinase. Bacteria which are resistant to penicillin are in some cases susceptible to large doses of the antibiotic. Bacteria which are penicillin-resistant but with individual cells sensitive to the action of the antibiotic form an important group: their sensitivity, as measured in the laboratory, may vary 1,000-fold or more according to the inoculum. Whether or not such organisms will be affected by large doses of penicillin would, therefore, seem to depend more on heaviness of infection than on resistance of the organism as determined by laboratory tests. Although the organism most commonly responsible for bacterial endocarditis in patients with rheumatic valvular disease or congenital lesions of the heart and vessels is Str. viridans, this organism poses little problem in therapy because-along with pneumoccoci, gonococci and group A hemolytic streptococci-strains of Str. viridans all are moderately or highly susceptible to penicillin therapy. Enterococci, which are relatively resistant to penicillin alone, now account for about 15 per cent of cases, contrasted with 4 or 5 per cent in the pre-antibiotic era. Endocarditis due to enterococci or coliform organisms occurs most frequently in patients with infections of the genitourinary or the intestinal tract or after various diagnostic or therapeutic procedures carried out in these areas. Most stubborn, chronic cases of bacterial endocarditis today are caused by staphylococci. Infection with staphylococci produces hypersensitivity toward these organisms: although the patient builds up a fair degree of immunity toward further overwhelming invasions of micrococci, paradoxically he responds with definite lesions to amounts of exotoxin so minute they would pass unnoticed in ordinary persons. Staphylococci have been

The effect of large doses of penicillin and streptomycin on the ammonia content of brain

Experiments on rats demonstrate that large doses of penicillin and streptomycin may cause changes in the content of ammonia in the brain (penicillin increases and streptomycin decreases the content). These changes are considered to be due to the effect of these antibiotics on the central nervous system (a stimulating effect of penicillin and a depressing one of streptomycin).

Staphylococcal endocarditis after mitral valvulotomy; report of three cases.

BACTERIAL endocarditis after cardiac surgery has been previously reported in 6 patients.1 2 3 4 5 Four had undergone mitral valvulotomy, the fifth had a transventricular commissurotomy for aortic stenosis, and the sixth had been operated on for pulmonic stenosis. In 2 of these cases, the organism proved to be an antibiotic-resistant staphylococcus, and the patients succumbed to the infection.1 , 2 In a third patient, whose blood culture had yielded a staphylococcus, large doses of penicillin, sulfisoxazole and chloramphenicol resulted in recovery.3 Pseudomonas aeruginosa was recovered from the blood and from the vegetations on the heart valves in the fourth case, reported in England by . . .

Unaltered penicillin susceptibility of streptococci; study of alpha hemolytic streptococci causing endocarditis, 1944 to 1954.

Members of the alpha hemolytic (viridans) group of streptococci, hereinafter referred to as alpha streptococci, are the commonest cause of subacute bacterial endocarditis and are also normal inhabitants of the human throat and gastrointestinal tract. Consequently, they are inevitably exposed to penicillin each time it is used in the treatment of any infection. It would seem, therefore, that, irrespective of the mechanisms involved, conditions favorable to the emergence of drug-resistant strains of alpha streptococci have been continuously operative for the past decade. In fact, the tentative acceptance of the idea that alpha streptococci have become less susceptible to penicillin is responsible in part for the present practice of using large doses of penicillin in the treatment of bacterial endocarditis. 1 Indeed, the apparently widespread loss of effectiveness of penicillin with respect to the micrococci has presented the grave question of whether this drug is losing its effectiveness in other infections.

Gastrointestinal hemorrhage due to rupture of aortic aneurysm into the esophagus.

Rupture of an aortic aneurysm into the gastrointestinal tract has been encountered twice at the Rhode Island hospital during the past 25 years. In one instance, the duodenum was involved, while in the other there was spontaneous rupture of an aneurysm of the descending aorta into the esophagus. This latter is the subject of our report, because it illustrates that the diagnosis of adrticoesophageal fistula should be considered in a patient with gastrointestinal hemorrhage, when an aneurysm of the thoracic aorta is also present. REPORT OF A CASE In September, 1951, a 65-year-old white man was admitted for the sixth time. His chief complaint was hematemesis of 36 hours' duration. He had been admitted to the hospital before because of central nervous system syphilis for which adequate, large doses of penicillin were administered. On admission, the patient was confused and was unable to give a coherent history. The only information