Mass exchange conditions in penicillin biosynthesis in an industrial fermenter with aerodynamic foam suppressor

The mass exchange characteristics of 50 m3 industrial fermentors with aerodynamic foam suppression and the effect of the specific power input on biosynthesis of penicillin were studied. A change in the specific power input from 1.3 to 1.9 kW/m3 had no effect on the level of the antibiotic accumulation when the medium with 8 per cent of lactose was used. An increase in the aeration rate from 1 to 1.2 m3/m3 X min provided a 1.1-fold increase in the penicillin activity of the fermentation broth. The use of the device for aerodynamic foam suppression with a system of automatic control of the partial pressure of dissolved carbon dioxide allowed decreasing 1.22-fold the oil use and increasing the process productivity by 10 per cent.     

Efficacy of penicillin therapy of meningococcal infection in children undergoing different regimes of pathogenetic therapy

The course of meningococcal infection and nonspecific and specific immunity in children subjected to different regimens of pathogenetic therapy were studied. It was shown that the clinico-immunological indices were more favourable in children treated with lasix as a diuretic agent. Recovery with defects was observed in 6.8 per cent of the children of this group, while in patients subjected to routine treatment the respective value amounted to 14.6 per cent. The use of lasix in combination with penicillin increased the efficacy of penicillin therapy and shortened the recovery period by 8.4 +/- 0.2 days as compared to that of routine treatment. No unfavourable effect of elevated penicillin concentrations on the lysozyme activity, blood bactericidal characteristics and composition of immunoglobulins A, M and G in the children was recorded.     

Epidemiological aspects of antibiotic resistance in hospital microorganisms

A total of 37490 medical histories of patients with "pure" and conditionally "pure" operations were analysed with a purpose of studying the scales of hospital infections in surgical inpatients and the effect of the prophylactic use of antibiotics on the frequency of postoperative complications. It was found that postoperative purulent complications developed in 10-25 per cent of patients. Antibiotics and mainly penicillin and streptomycin were used in the treatment of 75 per cent of patients before, during and after operations. The prophylactic use of the antibiotics in mass operations did not prevent the development of infections. Infiltrates and purulent wounds were more frequent (P less than 0.001) in patients subjected to the antibiotic prophylaxis. This indicates that the use of the antibiotics for preventing possible complications in patients with the "pure" operations and in the majority of patients with the conditionally "pure" operations is not advisable. The strategy of the rational use of antibiotics requires that the staff of the large hospitals should include a chemotherapeutist for defining the tactics of chemotherapy and controlling the use of antibiotics which should promote a decrease in the incidence of hospital infections and in the rate of lethality.     

STAPHYLOCOCCIC INFECTIONS IN CHILDREN

Over 50 per cent of all staphylococcic infections are hospital-acquired. In 92 per cent of hospital-acquired infection, the organism is resistant to penicillin, and in 74 per cent to tetracycline.Chloramphenicol, bacitracin, novobiocin and erythromycin are the drugs of choice for therapy. There was good correlation between clinical response and antibiotic therapy selected on the basis of results of organism sensitivity tests done by the agar diffusion technique.Cross-resistance among the tetracyclines averaged 94 per cent. Erythromycin and magnamycin showed similar pattern.Mortality in infants less than two months old was 7.8 per cent as compared with 1.1 per cent in older children. Death was related either to pneumonia or to septicemia in the ten fatalities recorded in this series.     

Subacute bacterial endocarditis; a report on 57 patients treated with massive doses of penicillin

Fifty-seven patients with subacute bacterial endocarditis were treated with doses of penicillin varying from 500,000 to 20,000,000 units per day. Diagnosis was confirmed in some cases by growths on blood culture, in others by postmortem examination. In those cases in which the diagnosis was established by blood culture, the in vitro sensitivity of the organism to penicillin was determined and penicillin then was administered by continuous intramuscular infusion in a dosage calculated to produce blood levels of penicillin four to five times that required for in vitro inhibition. Penicillin was given for a period of 21 days, and blood cultures were made periodically during and after treatment. Of the 57 patients, 38 were cured (66.7 per cent), and 19 died (33.3 per cent). Of the 19 who died, three did so within 48 hours of hospitalization and seven died despite adequate treatment. Of these seven, three died of cerebral emboli, two because of resistance to penicillin and streptomycin, one because of congestive heart failure, and one of undetermined cause. The remaining nine who died were considered to have been inadequately treated in that there was (1) failure to obtain sensitivity, (2) inadequate dossage of penicillin, (3) delay in starting treatment, or (4) failure to recognize mixed infections. There were five patients with repeatedly sterile blood cultures during life. In all of these cases, streptococcus viridans was recovered at postmortem examination. In an attempt to determine how long therapy should justly be withheld in patients with repeatedly sterile blood cultures, 140 cases of subacute bacterial endocarditis in which positive blood cultures had been obtained were reviewed. From the review it was determined that if blood cultures taken during the first two days are reported sterile, the chance of subsequent cultures proving positive is minimal. Therefore, for patients in whom the diagnosis seems otherwise obvious, delaying treatment for more than two days is not justified even though the blood culture be sterile. In cases in which blood cultures are repeatedly sterile, a dosage of 6,000,000 to 10,000,000 units of penicillin daily for 21 days is advisable.High bacterial resistance to penicillin and streptomycin was found in four fatal cases. In one of these, the infecting organism was streptococcus viridans, and in three it was staphylococcus albus. There was one patient with penumococcal meningitis complicated by unrecognized streptococcal viridans bacterial endocarditis.     

SUBACUTE BACTERIAL ENDOCARDITIS—A Report on 57 Patients Treated with Massive Doses of Penicillin

Fifty-seven patients with subacute bacterial endocarditis were treated with doses of penicillin varying from 500,000 to 20,000,000 units per day. Diagnosis was confirmed in some cases by growths on blood culture, in others by postmortem examination. In those cases in which the diagnosis was established by blood culture, the in vitro sensitivity of the organism to penicillin was determined and penicillin then was administered by continuous intramuscular infusion in a dosage calculated to produce blood levels of penicillin four to five times that required for in vitro inhibition. Penicillin was given for a period of 21 days, and blood cultures were made periodically during and after treatment.Of the 57 patients, 38 were cured (66.7 per cent), and 19 died (33.3 per cent).Of the 19 who died, three did so within 48 hours of hospitalization and seven died despite adequate treatment. Of these seven, three died of cerebral emboli, two because of resistance to penicillin and streptomycin, one because of congestive heart failure, and one of undetermined cause. The remaining nine who died were considered to have been inadequately treated in that there was (1) failure to obtain sensitivity, (2) inadequate dossage of penicillin, (3) delay in starting treatment, or (4) failure to recognize mixed infections.There were five patients with repeatedly sterile blood cultures during life. In all of these cases, streptococcus viridans was recovered at postmortem examination. In an attempt to determine how long therapy should justly be withheld in patients with repeatedly sterile blood cultures, 140 cases of subacute bacterial endocarditis in which positive blood cultures had been obtained were reviewed. From the review it was determined that if blood cultures taken during the first two days are reported sterile, the chance of subsequent cultures proving positive is minimal. Therefore, for patients in whom the diagnosis seems otherwise obvious, delaying treatment for more than two days is not justified even though the blood culture be sterile. In cases in which blood cultures are repeatedly sterile, a dosage of 6,000,000 to 10,000,000 units of penicillin daily for 21 days is advisable.High bacterial resistance to penicillin and streptomycin was found in four fatal cases. In one of these, the infecting organism was streptococcus viridans, and in three it was staphylococcus albus. There was one patient with penumococcal meningitis complicated by unrecognized streptococcal viridans bacterial endocarditis.     

Flora of the purulent foci of patients at an orthopedic traumatology clinic and its sensitivity to antibiotics

A total of 4664 bacteriological analyses of the wound and purulent discharge from orthopedo-traumatological patients were performed within a 6-year period, i.e. from 1971 to 1976. Staphylococci were the dominating microbes of the purulent-inflammatory foci. Its part in the monoculture amounted to 64.5--82 per cent. The specific weight of the monocultures of various microbes decreased during the last 3 years, while the number of the microbial associations increased from 11.6 to 25.4 per cent Staph. aureus predominated in the inflammatory processes (65.8 to 86.5 per cent). Still, during the last 3 years the number of Staph. epidermidis increased from 16.8 to 26.2 per cent. The number of the so called "intermediate" or dissociated type of Staphylococcus, i.e. Staph. albus usually amounted to 7.5--8.1 per cent. In 1976 its number was 12.5 per cent. The pathogenic microbes of the coccal group were usually sensitive to erythromycin, monomycin, levomycetin and kanamycin. Among these microbes only staphylococci preserved their sensitivity to penicillin. The causative agents of purulent processes, i.e. Escherichia, Proteus, Pseudomonas were resistant to most of the antibiotics. Sensitivity to monomycin was preserved by 50 per cent only in Proteus. The microbial associations were mainly sensitive to monomycin and kanamycin.     

Drug resistance of opportunistic enterobacteria isolated from various sources]

Resistance of 159 strains of opportunistic enterobacteria to 9 antibacterial drugs was studied. The strains were isolated from man and cattle. It was shown that the overwhelming majority of the isolates (93 per cent) were polyresistant irrespective of the genus. There was a high frequency of the strains resistant to the widely used antibiotics such as chloramphenicol (73 per cent), ampicillin (73.6 per cent) and rifampicin (95.6 per cent) and sulfanilamides (99.3 per cent). Gentamicin and nalidixic acid proved to be the most active against the cultures: 11.9 and 10 per cent of the resistant strains, respectively. The strains of enterobacteria isolated from different sources had a sensitivity to the antibiotics. Multiple antibiotic resistance to at least 5 drugs, variability of the spectra and high resistance were more characteristic of the isolates from the animals. The necessity of a rational use of antibacterial drugs in veterinary is indicated.     

CONGENITAL SYPHILIS IN CALIFORNIA

Routine serologic tests for syphilis (as required by California law governing prenatal examination) and penicillin therapy during pregnancy for infected mothers have been major factors in the prevention of congenital syphilis in California during the past ten years. In 1940 one of each 822 infants had the disease, as indicated by morbidity reports of congenital syphilis in infants under the age of one year. In 1950 the ratio was one in 8,148. To determine why congenital syphilis continues to occur, a study of the 134 cases reported over a two-year period was made with the cooperation of local health officers and practicing physicians. It showed that in 76 per cent of cases the mother did not consult a physician prior to delivery or reported so late in pregnancy that the infant was born before adequate penicillin therapy could be given. In another 15 per cent syphilis developed in the mother during pregnancy after a negative reaction to a prenatal serologic test. The other 9 per cent of cases were due to various factors, such as infectious relapse or reinfection in previously adequately treated mothers. The study indicated that most cases occur in the lower socioeconomic population groups. Seventy-four per cent of cases were in infants delivered in county hospitals.     

The management abscess of the lung

A review of the literature raises considerable doubt as to the advisability of surgical drainage of lung abscess as a definitive procedure. The mortality rate with use of this procedure and other hazards associated with it, must now be viewed in the light of improved methods of conservative therapy - involving the use of penicillin, bronchoscopic treatment and postural drainage-by which cure can be obtained in more than 80 per cent of cases of acute abscess and in a smaller proportion of cases of chronic abscess. Another factor to be considered is the better chance for diagnosis and effective resection of associated carcinoma when conservative treatment is employed.     

Effect of Growth Rate on the Synthesis of Penicillin by Penicillium chrysogenum in Batch and Chemostat Cultures

The kinetics of penicillin production by Penicillium chrysogenum Wis 54-1255 in a glucose-limited chemostat and in batch cultures are reported. The specific production rate of penicillin, q_pen (units per milligram of dry weight per hour) was independent of specific growth rate over the range 0.014 to 0.086 hr^-1. Growth was stopped by restricting the glucose supply to the “maintenance ration,” that is, the glucose requirement of the organism at zero growth rate with all other nutrients in excess. Under such conditions, the organism dry weight remained constant, but the q_pen fell approximately linearly to zero at a rate inversely related to the previous growth rate. Glucose supplied in excess of the maintenance ration inhibited the decay of q_pen. At a critical growth rate between 0.009 and 0.014 hr^-1, the decay was completely inhibited. Quantitative expressions for the q_pen of growing and nongrowing cultures were derived and used to predict the steady-state concentrations of penicillin accumulating in one- and two-stage continuous processes. A rational explanation of the kinetics of penicillin accumulation in batch cultures is given, relating the rate of penicillin synthesis to growth rate. It is concluded that an important role of corn steep liquor (CSL), a heterogeneous carbon and nitrogen source commonly used in penicillin production media, is the provision of substrates which allow a high concentration of mold to be reached before the growth rate falls below the critical value. CSL had no significant effect on q_pen.     

RHEUMATIC FEVER IN COLLEGE STUDENTS

The results of three independent surveys concerned with rheumatic fever and heart disease in students at the University of California were assembled and found to be in close agreement. A full 2 per cent of all students believed they had had rheumatic fever; and several times that proportion gave a history of one of the rheumatic manifestations. Only 0.25 per cent had demonstrable rheumatic heart disease and 0.1 per cent had congenital heart disease.Physiologic murmurs may occur in 3 per cent or more of students entering college.Penicillin prophylaxis is important in persons with rheumatic heart disease, but it is important not to put a label of rheumatic heart disease on persons who think they have had rheumatic fever but who have no demonstrable heart disease. Long term penicillin prophylaxis or other long term prophylactic procedures directed against rheumatic fever are not indicated unless the diagnostic criteria for rheumatic fever are clearly met or unless rheumatic heart involvement is definitely present.     

Gonococcal sensitivity to penicillin in women with gonorrhea relapse and reinfection]

Penicillin sensitivity of gonococci isolated from patients with relapses and reinfection of gonorrhea was studied. The results of the study were compared with those of the sensitivity tests in primary patients. The gonococcal strains with decreased sensitivity to penicillin were isolated from 82 per cent of the gonorrhea relapses, 47.8 per cent of the patients with reinfection and 33.2 per cent of the primary patients. The average sensitivity of the gonococcal strains isolated from the patients with relapses was 0.404 U/ml, while that in the primary patients and the patients with reinfection was 0.136 U/ml. Strains sensitive to 0.6--1.2 U/ml predominated among gonococci with decreased sensitivity in the patients with relapses, while in the primary patients and the ones with reinfection the value amounted to 0.1--0.2 U/ml. The penicillin sensitivity of gonococci may be used as a parameter in differential diagnosis of relapses and reinfection of gonorrhea.     

Constants of the Alper and Howard-Flanders oxygen equation for damage to bacterial membrane, deduced from observations on the radiation-induced penicillin-sensitive lesion

Energy deposited in the bacterial envelope of E. coli B/r induces lesions which are lethally attacked by penicillin in concentration insufficient to affect unirradiated bacteria. The critical lesions are probably in the membrane moiety. Bacteria were irradiated in the presence of 100 per cent oxygen, oxygen-free nitrogen and mixtures of 1.01, 0.59, 0.3, 0.1 and 0.06 per cent oxygen in nitrogen. Changes in sensitivity with pO2 conformed with the Alper and Howard-Flanders equation, for bacteria treated after irradiation by penicillin as well as for the untreated ones. The values of m were respectively 4.8 and 3.3; the values of K were identical, within experimental error, i.e. 4.4 mmHg. Sensitivity to induction of the penicillin-sensitive lesion was calculated from the difference in the reciprocals of D0 values proper to untreated and treated bacteria, for every gas used. The value of m could not be directly calculated because the effect of penicillin on anoxically irradiated bacteria was not detectable. For that reason, a transformation of the oxygen equation was used which allowed estimates to be made of both m and K, provided the results conformed with the equation. Within experimental error they did so conform. The calculated values of m and K for induction of the penicillin-sensitive lesion were respectively 8 and 5.9 mmHg, but it is shown that the oxygen enhancement ratio was probably underestimated and the K value overestimated. On the assumptions that these values of m and K are specific for radiation damage to bacterial membrane, and that radiation-induced killing is attributable to lethal lesions in the membrane as well as the DNA, the results demonstrate that any interaction of oxygen with sites of energy deposition in the DNA must play a very much smaller role in radiosensitization than does interaction with sites of energy deposition in the membrane.     

Sex selection technology utilization: further implications for sex ratio imbalance.

A survey of 242 undergraduates assessed attitudes toward use of sex selection technology and the choice of sex of first- and second-born offspring among potential users. Of our sample, 31 per cent endorsed use of sex selection technology, with the small subsample of nonwhites more accepting of utilization than were whites. There was a significant preference for first-born sons among all potential users, but nonwhites indicated a stronger preference than did whites. Students from rural areas were more desirous of boys than were urban residents. The desire for gender balance within the family documented in earlier studies did not manifest itself. Choice of gender of second child was independent of preference for first-born, with 54 per cent of the potential users desiring sons as both first and second children.     

MORTALITY RATES IN PATIENTS WITH BURNS—A Report of Experience at San Francisco City and County Hospital, 1943-1956

A review was made of the cases of 93 patients with burns covering more than 20 per cent of the body surface who were treated at the San Francisco City and County Hospital, University of California Service, between 1943 and 1956.The mortality rate increased from 40 per cent during 1943-1947 to 69 per cent during 1952-1956. A significant change in survival time was noted: During 1943-1947, 69 per cent of the deaths occurred within 48 hours of admission; during 1952-1956, only 19 per cent of the deaths occurred within the first 48 hours. In the period 1943-1947 the majority of deaths resulted from shock in the immediate post-burn period; in the later years of the study the major cause of death was infection.No patient more than 50 years of age who had burns of more than 25 per cent of the body surface survived. Only one patient with burns involving more than 45 per cent survived.No patient who had a blood culture positive for bacteria survived. The use of antibiotics had no effect on the incidence of infection. Elderly patients, children and alcoholics were less able to resist the effects of infection.The lowest mortality rate was in the age group of 15 through 35 years.     

Mortality rates in patients with burns; a report of experience at San Francisco City and County Hospital, 1943-1956

A review was made of the cases of 93 patients with burns covering more than 20 per cent of the body surface who were treated at the San Francisco City and County Hospital, University of California Service, between 1943 and 1956. The mortality rate increased from 40 per cent during 1943-1947 to 69 per cent during 1952-1956. A significant change in survival time was noted: During 1943-1947, 69 per cent of the deaths occurred within 48 hours of admission; during 1952-1956, only 19 per cent of the deaths occurred within the first 48 hours. In the period 1943-1947 the majority of deaths resulted from shock in the immediate post-burn period; in the later years of the study the major cause of death was infection. No patient more than 50 years of age who had burns of more than 25 per cent of the body surface survived. Only one patient with burns involving more than 45 per cent survived. No patient who had a blood culture positive for bacteria survived. The use of antibiotics had no effect on the incidence of infection. Elderly patients, children and alcoholics were less able to resist the effects of infection. The lowest mortality rate was in the age group of 15 through 35 years.     

Penicillin formation by biochemical mutants of Penicillium chrysogenum and their spontaneous revertants

The capacity for the antibiotic production in the auxotrophs of Penicillium chrysogenum with various deficiency and their revertants was studied. It was found that the capacity for penicillin synthesis was impaired to various degrees in the majority of the auxotrophs. Variants with the penicillin production levels by 13--20 per cent higher than those in the initial prototrophic strain were isolated for the first time in selection of the eukaryotes with the method of obtaining highly active revertants from auxotrophs according to the scheme "prototroph-auxotroph-prototroph".     

Oral bacteria resistant to mercury and to antibiotics are present in children with no previous exposure to amalgam restorative materials

Dental plaque from 76 children without amalgam restorations was screened for bacteria resistant to mercuric chloride. Seventy-one per cent of the children harboured mercury-resistant oral bacteria and the median percentage of the total oral microflora resistant to mercuric chloride was 0.007% (range 0-5.3%). Eighty-seven mercury-resistant bacteria were isolated and 86% of these were streptococci with Streptococcus mitis predominating. Sixty per cent of the mercury-resistant isolates were also resistant to at least one of the four antibiotics tested (penicillin, ampicillin, erythromycin and tetracycline) with resistance to tetracycline (40% of isolates) most frequently encountered.     

Side effects of antibiotics in rheumatic diseases]

Complications due to antibiotic therapy in rheumatic patients subjected to season bicillin prophylaxis in Minsk within 1965--1975 and in patients with extensive collagenoses were studied. Allergic complications mainly ih the form of allergic reactions in the patients treated with bicillin-3 or picillin-5 were observed in 7.8--16.8 per cent of the patients. Within 10 years 52 cases of anaphylactic shock due to the bicillin use were recorded. Side reactions to antibiotics were observed in 16 (17.3 per cent) out of 92 patients with extensive collagenoses. For prophylaxis of the above complications it is recommended to use rational antibiotic therapy in rheumatic patients, strict registration of allergological states in the anamnesis, testing of microbial sensitivity to the antibiotics.