Antimicrobials

Orthop Clin North Am, 1975 Oct, 6(4), 965 - 72
Puncture wounds of the foot; Fitzgerald RH Jr et al.; Serious complications occurred in 29 of 887 children with puncture wounds of the feet treated over a four-year period at the Dr . Charles A . Janeway Child Health Centre . Osteomyelitis in one of the small bones of the foot was the commonest complication and occurred when a cartilaginous surface (physeal plate or articular cartilage) had been violated . Although systemic signs of osteomyelitis frequently are absent, this infectious process is refractory to medical management . The combined surgical and medical management of this complication is outlined . Management of puncture wounds in the emergency room should include a thorough history concisely recorded, tetanus prophylaxis, and cleansing, debridement, and probing of the wound . Antimicrobial agents are not routinely required but should be reserved for patients presenting late with cellulitis or an established infection . A semisynthetic penicillinase-penicillin appears to be the agent of choice until the results of microbiologic studies are available.

Can J Comp Med, 1975 Oct, 39(4), 416 - 20
In vitro antimicrobial sensitivity of Mycoplasmas isolated from the bovine genital tract; Truscott RB et al.; The in vitro antimicrobial sensitivity of 14 mycoplasma and 13 ureaplasma strains isolated from the genital tracts of bulls was examined . It was found that at relatively low concentrations, tetracycline, declomycin and tylosin were lethal to both types of organisms . Lincospectin, berenil, streptomycin and erythromycin were lethal to mycoplasmas but were only inhibitory to the ureaplasma strains at the same concentrations . Polymyxin B and novobiocin were ineffective at the levels tested.

Lab Anim Sci, 1975 Oct, 25(5), 570 - 4
Efficacy of lincomycin and spectinomycin on canine pathogens; Hamdy AH; Lincomycin (L), spectinomycin (S), and both (L-S) were evaluated in vitro and vivo against canine pathogens . In vitro, a wider spectrum of antimicrobial activity was achieved with L-S than with either L or S . The therapeutic effects of the antibiotics were investigated in 36 dogs inoculated with a mixture of the microbal agents . Tonsillitis, conjunctivitis, laryngitis, abscess formation, and necropsy findings were measured . The L-S combination was effective for the treatment of tonsillitis, conjunctivitis, laryngitis, and pneumonia in dogs.

Am J Ophthalmol, 1975 Sep, 80(3 Pt 2), 509 - 12
Bacterial endophthalmitis following suture removal after penetrating keratoplasty; Forstot SL et al.; Of three cases of bacterial endophthalmitis occurring after removal of corneal sutures following penetrating keratoplasty, two were associated with wound dehiscence and one was not . Factors that may predispose to wound dehiscence and subsequent infection are: use of fine suture material, corticosteroids, and chronic topical antibiotics; early removal of corneal sutures; lack of adherence to strict asepsis prior to and after suture removal; and open suture tracts that may be kept open by incarceration of vitreous strands . Late corneal wound dehiscence may occur with subsequent development of endophthalmitis as long as three days after suture removal . The use of topical antibiotics before and after suture removal may decrease the potential for infection . In addition, early recognition of intraocular infection by the patient and the surgeon for immediate institution of antimicrobial and anti-inflammatory therapy may preserve useful vision.

Arzneimittelforschung, 1975 Sep, 25(9), 1336 - 9
{Antimicrobial action of potential isothiocyanate forming substances 7th communication (author's transl)}; Zsolnai T; A number of (N-aryl-dithiocarbamino)-alkanecarbonic acids bearing halogen substituents and related compounds are described which may be considered potential isothicyanate forming substances . The in vitro fungistatic activity of these compounds was investigated and the results obtained compared with those of captan and thiram . It was demonstrated that the halogen substituted (N-aryl)-dithiocarbamino)-alkanecarbonic acids exert an intensive fungistatic effect with a wide spectrum of activity and that the most active of them are equal to captan and thiram.

J Antibiot (Tokyo), 1975 Sep, 28(9), 636 - 47
A new antibiotic, fumaramidmycin I . Production, biological properties and characterization of producer strain; Maruyama HB et al.; A new antibiotic, fumaramidmycin, has been isolated from a streptomycete NR-7GG1 which was characterized and named Streptomyces kurssanovii . The strain produced the antibiotic only when grown on agar plates but not in the submerged culture broth, where the contact with the vegetative mycelia appears to cause the inactivation of the antibiotic . The antibiotic shows an antimicrobial activity against both Gram-positive and Gram-negative bacteria.

Ann Trop Med Parasitol, 1975 Sep, 69(3), 359 - 71
The experimental chemotherapy of leishmaniasis . II . The activity in tissue culture of some antiparasitic and antimicrobial compounds in clinical use; Mattock NM et al.; A variety of compounds used in the treatment of parasitic or bacterial infections in man, including leishmaniasis itself, were examined for their activity against three lines of Leishmania in tissue culture . The organisms used were L . mexicana mexicana, L . tropical major and L . donovani; they were grown in dog sarcoma and hamster peritoneal exudate cell lines . Leishmanicidal activity was observed in a number of compounds currently in clinical use for the treatment of one or other form of leishmaniasis . Cycloguanil, nifurtimox, amphotericin B and monomycin were effective but pentamidine showed poor activity . In each case marked differences were observed in the level of response in the different parasite lines . Organic antimonials were most active when anmastigotes were exposed to them prior to entry of the parasites into host cells . This suggests that such compounds may exert an effect on amastigotes during their brief extracellular transit from one host cell to another in vivo . A number of antimalarials showed good to moderate leishmanicidal action, particularly against L . mexicana and L.t . major . Several schistosomicidal agents also possessed leishmanicidal properties . The commonly used broad spectrum antibiotics showed little if any activity . In discusssion a comparison is drawn between data published on the action of some of these drugs against L.t . major in mice and our observations with the same strain and L . mexicana in tissue culture . A remarkably good agreement is found for most of the compounds examined . General agreement is also noted between these data and reports of clinical trials although it is not possible to draw too many conclusions because of the failure in most clinical studies to make an accurate identification of the causative Leishmania . It is concluded that, although the tissue culture model is not to be considered as ideal and can probably be improved, data obtained by its use do bear relevance to the action compounds in vivo, and the model may be use in the screening of drugs for leishmanicidal activity.

Arzneimittelforschung, 1975 Sep, 25(9), 1382 - 5
Relationship between the chemotherapeutic effectiveness of ciclacillin and ampicillin and the time of their administration in experimental infections; Arend P et al.; In an attempt to explain the discrepancy between the weak in vitro activity and good clinical efficacy of ciclacillin, a time-dosage-efficacy study was made in order to investigate the relationship of the effectiveness of this antibiotic to the interval between experimental infection and administration in comparison to ampicillin, which because of its similar antimicrobial spectrum and completely different pharmacokinetic properties was particularly suitable for use in the study . Various single oral doses of both antibiotics were administered once to NMRI (SPF) mice at various intervals (0, 1, 2 or 3 h) following experimental infection with E . coli WT 102, E . coli 3033 or E . coli 026:B6 and the CD50's determined and compared statistically . It was demonstrated that the chemotherapeutic effectiveness of both antibiotics was markedly dependent on the interval between experimental infection and administration . Whereas ampicillin was superior to ciclacillin when drug and infective organism were administered simultaneously (0 h), ciclacillin was superior to ampicillin when it was administered 3 h after experimental infection . Both antibiotics were about equally effective when administered 1 or 2 h after infection . The difference in the serum concentrations and rates of absorption and excretion of the two drugs is assumed to be the reason for this phenomenon, and the pharmacokinetic characteristics of ciclacillin, in particular its rapid and almost complete absorption and rapid attainment of high peak serum levels, are discussed as at least a partial explanation of the difference in its in vitro and in vivo activities.

Schweiz Med Wochenschr, 1975 Aug 16, 105(33), 1047 - 51
{Use of drugs in the hospital . Retrospective model study}; Wolfangel U et al.; This study sets out to describe and evaluate antimicrobial therapy in the departments of surgery, medicine, gynecology and obstetrics of a 500-bed general hospital serving a mainly metropolitan population . About one third (605) of 2002 hospitalized patients received chemotherapy, 97 patients being treated for nosocomial infections . In 44% antimicrobials were given prophylactically, chiefly in the surgical department (in 60% of the drug courses) and the departments of gynecology (in 78%) and obstetrics (in 71%) . Combinations (excluding sulphamethoxazole/ trimethoprim) were used on the medical wards in 5% and on the surgical wards in 15% of the drug courses . Gentamycin combined with beta-lactam antibiotics was most often used in medicine, while penicillin/streptomycin and ampicillin/cloxacillin in fixed ratios were the most frequent combinations in surgery . Finally, each therapy was evaluated by two experts as either rational, irrational or questionable . 61% of the 681 drug courses were considered rational, 16% questionable and 23% irrational . In the 155 irrational drug courses, one or more of the following criticisms were made: inappropriate chemoprophylaxis (101), wrong drug in chemoprophylaxis (66), inappropriate combination (30), wrong drug in symptomatic chemotherapy (28), no bacteriological diagnosis (26), sensitivity test not considered (17), use of antagonistic combinations (11) and wrong drug in therapeutic chemotherapy (5).

N Z Med J, 1975 Aug 13, 82(545), 83 - 5
Antibiotic sensitivity of pathogens from infected skin lesions; Bremner DA et al.; One hundred and seven patients attending an accident and emergency department with infected skin lesions were studied . The commonest organisms isolated were Staph aureus and Strep pyrogenes . Routine antimicrobial sensitivity testing of bacterial isolates showed that the antibiotic most likely to be effective against the organisms isolated was a cephalosporin or a tetracycline.

Ann Intern Med, 1975 Aug, 83(2), 212 - 4
Bacteremia with upper gastrointestinal endoscopy; Shull HJ Jr et al.; Fifty patients undergoing upper gastrointestinal fiberoptic endoscopy were studied prospectively for the development of bacteremia by aerobic and anerobic blood cultures obtained before, during, and at 5 and 30 minutes after the procedure . Forty-six patients were culture negative; four had positive cultures at 5 or 30 minutes after the procedure, or at both times . The level of bacteremia as estimated by pour plates was very low . Bacteremia did not correlate with the performance of biopsy or the type of mucosal abnormality found . It is concluded that only very high-risk patients should receive antimicrobial prophylaxis before this procedure . The minor risk of this low-level bacteremia should not be considered a contraindication to the performance of upper gastrointestinal endoscopy.

Am J Med, 1975 Aug, 59(2), 219 - 23
Penetration of antimicrobial agents into bronchial secretions; Wong GA et al.; The entry of ampicillin, cephalothin and gentamicin into traceobronchopulmonary secretions/exudates was assessed in 22 patients during 28, episodes of pneumonia or bronchitis . Specimens were collected from the lower respiratory tract via tracheostomies or endotracheal tubes using either the flexible fiberoptic bronchoscope (50 specimens) or an intratracheal catheter (59 specimens) . Venous blood was obtained at the same time . The concentrations in the bronchial specimens were less than those in the corresponding serums, amounting to about 10 per cent with ampicillin, 25 per cent with cephalothin and equal to or greater than 40 per cent with gentamicin.

J Lab Clin Med, 1975 Aug, 86(2), 349 - 59
Radioimmunoassay, acetylating radio-enzymatic assay, and microbioassay of gentamicin: a comparative study; Stevens P et al.; Gentamicin is an aminoglycoside antibiotic widely used to treat gram-negative bacillary infections . Because it has a low therapeutic index, monitoring of serum levels may help to insure adequacy of dosage and avoid toxicity . Microbiological assays are relatively slow and can be complicated by the presence of other antimicrobials . Radioimmunoassay (RIA) and acetylating radio-enzymatic assay (ARA) are new methods for gentamicin assay which offer the following advantages: rapidity (less than 3 hours); no interference by other antibiotics; RIA is extremely sensitive and ARA is versatile (being useful in the measurement of other aminoglycosides) . Correlation coefficients determined by linear regression analysis of assays on 36 patient samples performed in duplicate on 2 different days demonstrated no significant difference in measurement of gentamicin by each of the methods . Factors such as numbers of specimens, cost, and time involved will affect the decision of the method to be applied in individual laboratories.

Arch Dermatol, 1975 Aug, 111(8), 1004 - 10
Aluminum chloride in the treatment of symptomatic athelete's foot; Leyden JJ et al.; Various aluminum salts were evaluated for in vitro and in vivo antimicrobial activity and ability to bind with serum proteins (astrigency) with the object of finding a colorless substance to substitute for carbol-fuchsin solution (Castellani paint) in the treatment of symptomatic interdigital athlete's foot . Aluminum chlorohydrate was more powerful in killing bacteria and fungi than aluminum acetate and aluminum chloride . However, aluminum chloride showed pronounced astringency and was the only compound to bring about rapid resolution of the signs and symptoms of athlete's foot in open-ended clinical trials . This salt promptly controls odor, pruritus, and maceration . The beneficial effect depends largely on drying the surface, not killing organisms . A solution of 30% aluminum chloride was found to be equlvalent to carbol-fuchsin solution in effectively treating symptomatic athlete's foot.

Cancer, 1975 Aug, 36(2), 813 - 20
Support systems for the patient with cancer: future prospects; Levine AS; Bleeding and infection are the usual proximate causes of morbidity and mortality in patients with hematologic malignancy and many solid tumors . The most important cause of bleeding is thrombocytopenia . The use of immunologically matched platelets has rendered this complication less frequent . Host defenses against infection are often compromised unavoidably as a function of the primary disease and its therapy . However, it is important to note that many infections are caused by hospital-acquired organisms; a significant number of infections can be avoided with meticulous attention to possible breaches of the host barriers against invasion . Diagnosis and treatment of infection in the altered host are urgent and demanding, since the median survival with inappropriate therapy of bacterial sepsis is less than 3 days . Newer diagnostic techniques, such as the gallium scan, are helpful, as are antimicrobial combinations used empirically . Experimental approaches to the prevention of infection include antibacterial vaccines, the use of laminar air-flow isolation, and transplantation of bone marrow . Experimental approaches to the therapy of infection include leukocyte transfusion and the use of transfer factor . A discussion of supportive care must also include consideration of the psychosocial concomitants of the cancer process, particularly those factors in the doctor-patient relationship which promote anxiety in the physician to the end that his support of the patient is not effective.

Br J Vener Dis, 1975 Aug, 51(4), 257 - 64
Activity of eight antimicrobial agents in vitro against N . Gonorrhoeae; Stolz E et al.; The sensitivity of four groups of gonococcal strains to ampicillin (Am), penicillin (P), tetracycline (T), rifampicin (Ri), spectinomycin (Sp), sulphamethoxazole (Su), trimethoprim (Tr), and a combination of Su and Tr in the ratio 5:1 (Su/Tr 5:1) has been determined . The various groups of strains were isolated from male civilians (MC), female civilians (FC), and sailors (S) in Rotterdam (R) in 1972, and from FC in Amsterdam (A) in 1967 . The S-R strains, which may be regarded as mainly imported, were compared with the MC-R and FC-R (which may be considered as mainly of Dutch origin) . Also investigated was whether the incidence of relative resistance to the antibiotics investigated among Dutch strains has changed in the period from 1967 to 1972 . For this purpose, the FC-A and FC-R strains were compared . The MC-R and FC-R strains were also compared with one another . Finally, Spearman's rank correlation coefficient r were calculated between the sensitivity distributions for each pair of antibiotics investigated, for all strains . The S-R strains were significantly less sensitive to Am, P, T, Ri, and Tr than the MC-R and FC-R strains . Comparison of the FC-A and FC-R strains revealed that the FC-R strains were significantly less sensitive only to Su/Tr 5:1 . A possible explanation for this finding is given . With the exception of one FC-A strain, all gonococcal strains were sensitive to Sp . High values of r (larger than or equal to 0.50) were found between Am and P, Am and T, and P and T for all groups of strains . The values of r between any pair of the antibiotics Am, P, T, Ri, and Tr (with the exception of the pair Am-P) were always highest for the S-R strains . High values of r (larger than or equal to 0.50) were found between Su and Su/Tr 5:1 for all groups of strains . The FC-A strains, unlike the R strains, gave low values of r between Su and Tr and between Tr and Su/Tr 5:1 . A possible explanation for this is given . Finally, a hypothesis is put forward to explain the fact that no significant changes were found in the sensitivity of Dutch gonococcal strains to Am, P, T, Ri, Sp, Su, and Tr in the period from 1967 to 1972, while the S strains (which may be regarded as imported) showed a significantly higher percentage of strains relatively resistant to Am, P, T, Ri, and Tr.

J Pharm Sci, 1975 Jul, 64(7), 1259 - 62
Synthesis and antimicrobial activity of N-substituted N'-cyano-S-(triorganostannyl)isothioureas; Kupchik EJ et al.; Six N-substituted N'-cyano-S-(trimethylstannyl)isothioureas were synthesized by the reaction of (trimethylstannyl)cyanamide with various organic isothiocyanates . The IR spectrum of each compound was obtained over the 4000-30-cm(-1) range, and some bands were assigned . The six new compounds and five previously synthesized N-substituted N'-cyano-S-(triphenylstannyl)isothioureas were tested for and were found to exhibit antifungal activity . N-Phenyl-N'-cyano-S-(triphenylstannyl)isothiourea was also investigated for antibacterial activity and was observed to be especially inhibitory toward Gram-positive species . The antimicrobial activity of two compounds was compared to that of the oxygen analogs of these compounds.

Am Rev Respir Dis, 1975 Jul, 112(1), 31 - 6
Response to chemotherapy of pulmonary infection due to Mycobacterium kansasii; Harris GD et al.; Chemotherapy of pulmonary disease due to Mycobacterium kansaii has not always been successful, and resectional surgery has been used frequently in the treatment of this infection . To ascertain the impact of new antimicrobial agents on the treatment of M . kansaii infection, we reviewed the clinical courses of 59 patients treated between 1971 and 1974 . Over-all, 92 per cent of patients converted their sputum cultures while receiving drugs, with only one patient undergoing surgical resection . Regimens containing rifampin were universally effective in both initial and retreatment cases; however, they offered no significant advantage over monrifampin regimens in initial treatment cases . In vitro resistance to isoniazid and ethambutol did not adversely affect the results of treatment with these drugs . Owing to the effectiveness of current chemotherapy, parameters such as age, underlying lung disease, or extent of disease were not related to the outcome of therapy . Because 90 per cent of the conversions in successful regimens occur within 4 to 6 months of beginning therapy, patients whose cultures remain positive should be considered for alternate drugs . Because the frequency of relapse after current chemotherapy is not yet clear, and because rifampin appears to be particularly advantageous in retreatment programs, rifampin should be reserved for this role . The total course of treatment should probably span at least 18 months, or 6 months beyond any cultural or radiographic evidence of activity.

J Med Chem, 1975 Jul, 18(7), 708 - 13
Synthesis and biological activity of some antitumor benzophenanthridinium salts; Stermitz FR et al.; A facil synthesis of benzophenanthridinium salts has been developed and used for preparing a number of these compounds . The antitumor activities in mouse leukemia L1210 (LE) and P388 (PS) were determined as well as some selected antimicrobial activities . Although antitumor activity was exhibited by several of the derivatives, none was as active as the naturally occurring alkaloid fagaronine . Fagaronine was made available as a synthetic by an improved procedure . Some structure-activity relationships among antitumor benzophenanthridinium salts are discussed.

JAMA, 1975 Jun 23, 232(12), 1243 - 60
Chronic obstructive airway diseases . Current concepts in diagnosis and comprehensive care; Hodgkin JE et al.; Physicians and paramedical personnel often find the early diagnosis and differentiation of obstructive airway diseases to be a challenging problem . The history and physical examination are often not enough to allow the physician to detect either the presence of, or determine the type of, disease present . Patterns of pulmonary function abnormality to determine the presence of obstructive or restrictive defects are discussed . Guidelines useful in the differentiation of obstructive airway diseases are presented . Once a patient with COAD is assessed, the physician needs to outline a therapeutic program after establishing goals with the patient . These goals include (1) improved ability for the patient to achieve relief from symptoms and (2) improved capacity to carry out the activities of daily living . The therapeutic modalities available for the comprehensive care of patients with COAD are discussed . These include general factors such as patient and family education, avoidance of smoking and other inhaled irritants, avoidance of infection, a minimum stress environment, high fluid intake, and proper nutrition . The appropriate use of the medications most commonly employed in the teatment of these patients, eg, bronchodilators, expectorants, antimicrobials, corticosteroids, cromolyn, digitalis, and diuretics, are individually discussed . The use of such respiratory therapy techniques as aerosol therapy, intermittent positive pressure breathing, and oxygen therapy are considered . Application of the specialty of rehabilitation medicine to patients with obstructive airway disease is described . This includes physical therapy with breathing retraining, clapping and postural drainage, and exercise reconditioning, occupational therapy with attention to energy conservation in activities of daily living, psychological considerations, and vocational rehabilitation . Definite benefits that can be demonstrated if the physician employs this type of systematic respiratory care program include a decrease in the frequency and duration of hospital admissions, socioeconomic gains from reduced hospitalizations, a reduction in anxiety, depression and somatic concern, the return of patients to positions of employment and the establishment of a better quality of life . Persistence in making sure the patient continues in a systematic program, including both pharmacological and nonpharmacological modalities, may be the means of assuring maintenance or even improvement in his health . The day-to-day treatment for the majority of patients should remain in the hands of the primary physician . However, community resources must be established to allow the primary physician to provide these patients with adequate comprehensive respiratory care . Development of three levels of care (the primary physician, community respiratory rehabilitation units, and the regional respiratory center) should make superior respiratory care available to every patient with obstructive airway disease.

Can Med Assoc J, 1975 Jun 21, 112(12), 1428 - 9
Antibiotic abuse: the testimony of medical students; Perry TL; Surveys of the use of antimicrobial drugs on students during antimicrobial drugs on students during their first 15 months in medical or dental school indicate that they have been treated with these agents at least three times as frequently as seems reasonable, and that the tetracyclines, ampicillin, penicillin G and erythromycin are the chief drugs overused . Antimicrobiol therapy is frequently instituted for probable viral respiratory tract infections and without any attempt to establish a bacteriologic diagnosis . It is likely that anitmicrobiol agents are used more widely in treating the general public in Canada than in treating medical students . Improvements in the rational use of this important group of drugs could increase the quality and probably reduced the cost of medical care.

J Pharm Sci, 1975 Jun, 64(6), 982 - 6
Electronic spectra and electronic structures of some antimicrobials derived from proflavine; Schulman SG et al.; The shifts in the absorption and fluorescence spectra of 3-aminoacridine, proflavine, acridine orange, and acridine yellow were employed to show that the singly charged cations, the predominant species at biological pH, exist in the ground state in the amino form . In the lowest excited singlet state, however, the monocations of the diaminoacridines have the imino structure, a conclusion supported by the relative ground- and excited-state pKa values of the reactions of the monocation with H-+ . The ground-state amino structure has its positive charge concentrated at the heterocyclic nitrogen atom, a fact that is of primary importance in determining the geometry of binding to DNA.

Zentralbl Bakteriol {Orig A}, 1975 Jun, 232(1), 119 - 28
{Newer antimycotics . I . Derivatives of phenyl-hydrazine (author's transl)}; Zsolnai T; The author produced a number of derivatives of phenyl-hydrazine and its analogues, investigated their antimicrobial efficiency in vitro, and discussed the association of chemical structure with the fungistatic effect in the series of phenyl-hydrazine-derivatives . From the author's results it can be concluded that the halogen-substituted phenyl-hydrazines and their N-(acetyl)-derivatives exert a moderate fungistatic effect (Tab . 1) . In the series of N-aryl-sulphonyl-N'-phenyl-hydrazines only the compounds derived from 3,4-dichloro-phenyl-hydrazine proved to be effective; the other representatives of this type were fully ineffective (Tab . 1) . The majority of the halogen-substituted N-aroyl-N'-phenyl-hydrazines exerted a relatively strong fungistatic activity with a broad spectrum of efficiency (Tab . 2) . On the contrary, their analogues having a -CO-NH- group in place of the -CO-NH-NH-group, were fully inactive (Tab . 3) . From the investigated derivatives of phenyl-hydrazine, the N-benzoyl-, N-(2-chloro-benzoyl)-, N-(4-chloro-benzoyl)- and N-furoyl-derivatives of 3- and 4-chloro-phenyl-hydrazine, furthermore the N-benzoyl- and N-furoyl-derivatives of 3,4-dichloro-phenyl-hydrazine were most effective (Tab . 2) . The acute toxicity in the mouse of these effective compounds was relatively small; they were found to be significantly less toxic than tetramethyl-thiuramdisulfide (Tab . 4) . On the basis of an intensive fungistatic efficiency and small toxicity of the halogen-substituted N-aroyl-N'-phenyl-hydrazines, it seems that a number of representatives of these types of chemical compounds could be given a role in the chemotherapy of superficial human and animal dermatomycoses, and also in the chemoprophylaxis of certain phytomycoses.

J Med Chem, 1975 Jun, 18(6), 625 - 7
Monocyclic antibiotic beta-lactams; Abdulla RF et al.; The preparation and antimicrobial activity of a series of beta-lactams (3a-f) are described . These compounds were prepared from the 2+2 cycloaddition of beta,beta-disubstituted enamines with aryl isocyanates; compounds 3a-f underwent facile beta-lactam ring fission between aminal carbon atom C4 and the lactam nitrogen N1 . The resisting formylacetanilide derivatives were devoid of antibiotic activity.

Int Surg, 1975 May, 60(5), 275 - 7
Silver sulfadiazine for control of burn wound infections; Fox CL Jr; Silver sulfadiazine (Silvadene, U.S.; Flamazine, U.K.; Flammazine, N.; Sulplata, S.A.) is the newest topical antimicrobial agent available following worldwide clinical trials . Good control of infection is achieved without pain or other demonstrable side effects, using either dressings or the exposure technic . Many burned areas kept free of infection heal without grafting . Where necessary, early preparation for and good take of grafts has been attained by utilizing this new therapeutic agent . Markedly reduced mortality from burn wound sepsis has generally been observed.

J Clin Microbiol, 1975 May, 1(5), 425 - 8
Association of Pseudomonas cepacia with chronic granulomatous disease; Bottone EJ et al.; Pseudomonas cepacia was recovered from a number of infected sites in three patients with chronic granulomatous disease of childhood . The organisms were identified on the basis of their oxidative utilization of a variety of carbohydrates and their positive beta-galactosidase and oxidase activities . They were resistant to most antimicrobial agents and moderately susceptible to chloramphenicol . Peripheral blood leukocytes isolated from two siblings with chronic granulomatous disease, including one of the patients in this series, failed to kill P . cepacia in vitro . Prolonged prophylactic and antimicrobial therapy may well have played a significant role in the colonization and infection of these patients with P . cepacia.

Ann Thorac Surg, 1975 May, 19(5), 592 - 604
Opportunistic endocarditis following open-heart surgery; Norenberg RG et al.; The incidence of endocarditis following open-heart operations is declining, but the relative incidence of endocarditis by the opportunistic organisms, both bacterial and fungal, has increased . These "opportunists" require careful identification and sensitivity testing so that appropriate therapy can be planned . In cases of candida endocarditis, a positive precipitin test and elevated candida antibody titer may provide an earlier means of diagnosis than blood cultures . These patients should be treated promptly with adequate dosages of specific antimicrobial or antifungal agents . Reoperation should be considered early if there is evidence of valve dehiscence or embolic phenomena or if drug therapy fails to control the infection.

Am Rev Respir Dis, 1975 May, 111(5), 703 - 5
The activity of chaulmoogra acids against Mycobacterium leprae; Levy L; The activity of the crude sodium salts of the fatty acids of chaulmoogra oil and of hydnocarpic and chaulmoogric acids against Mycobacterium leprae was studied in mouse footpad infection . Multiplication of the organisms was inhibited when the salts were administered intraperitoneally and subcutaneously 3 times per week, and when chaulmoogric acid was administered intraperitoneally 5 times per week in half the equivalent dose . Dihydrochaulmoogric acid was also active, whereas palmitic acid was not . Hydnocarpic acid administered intraperitoneally once per week in a dose equivalent to half that of the sodium salts of the chaulmoogra fatty acids was not effective . The demonstration that chaulmoogra fatty acids possess activity against M . leprae lends weight to our earlier suggestion that a study of compounds analogous to these acids may yield effective antimicrobial agents with a unique mechanism of action.

Am J Surg, 1975 May, 129(5), 537 - 44
Proteolytic enzymes as adjuncts to antimicrobial prophylaxis of contaminated wounds; Rodeheaver G et al.; When a tissue is injured, its vessels exhibit a marked increase in vascular permeability . Blood proteins, including fibrinogen, traverse the vessel walls and lead to the development of a surface coagulum . This inflammatory response continues until primary closure of the wound edges is accomplished . The thickness of the surface coagulum is roughly proportional to the time interval between wounding and closure . This coagulum encompasses the surface contaminants, preventing contact with either topical or systemic antibiotics . The presence of this surface coagulum limits the time in which antibiotic prophylaxis is effective . At three hours after injury, antimicrobial prophylaxis of contaminated wounds has no therapeutic value . Hydrolysis of the protein coagulum by proteolytic enzymes enhances the activity of the antibiotic in experimental wounds . The success of proteolytic enzymes as adjuncts to delayed antibiotic treatment can be correlated with the clot lysis activity of the enzymes in vitro . Travase, the most potent fibrinolytic enzyme, is the most effective adjunct to delayed antibiotic therapy of contaminated wounds . In contrast, the active enzymes found in Elase, which exhibit no significant clot lysis activity in vitro, do not potentiate the activity of antibiotics in wounds subjected to a delay in treatment . Travase prolongs the period of effective topical antibiotic action for at least eight hours in experimental contaminated wounds . The therapeutic merit of Travase is also apparent when the antibiotic is administered systemically . Travase shows promise as an adjunct to a variety of antibiotics that are effective against both gram-positive and gram-negative organisms . The results of these experimental studies support our belief that clinical studies support our belief that clinical studies should now be initiated to test the therapeutic value of Travase as an adjunct to antibiotics in heavily contaminated wounds subjected to an unavoidable delay in treatment.

Am Rev Respir Dis, 1975 May, 111(5), 651 - 5
Inhibition of multiplication of Mycobacterium leprae by several antithyroid drugs; Levy L et al.; Multiplication of Mycobacterium leprae in the mouse footpad was inhibited when mice were fed, mixed in their diet, 0.05 per cent methimazole, 0.066 per cent USP thyroid powder, methimazole plus thyroid powder, 0.15 per cent 5-n-heptyl-2-thioxo-4-thiazolidinone, 0.1 per cent propylthiouracil, and 0.1 per cent thambutosine for 154 days, beginning on the day of inoculation . All of the treatment regimens, except for the 2 containing thyroid powder, decreased the plasma concentrations of thyroxine and protein-bound iodine . It is suggested that the 2 antithyroid drugs, methiomazole and propylthiouracil, and the 2 antimicrobial agents, heptylthioxothiazolidinone and thiambutosine, all of which possess structural features in common, may exert the antithyroid and antimicrobial effects through a common mechanisms.

Ann Intern Med, 1975 Apr, 82(4), 571 - 6
Brain abscess: a review of recent experience; Brewer NS et al.; From 1961 through 1973, 60 patients with brain abscess were treated at the Mayo Clinic by surgical excision and antimicrobial therapy . The operative mortality was 17%, which was identical to a similar series reported in 1959 . The patients who had the diagnosis of brain abscess confirmed at autopsy and who never underwent operation (24 patients) were more elderly than the group operated on, and a higher percentage had multiple brain abscess . Severe systemic disease or multisystem disease, or both, usually precluded a vigorous surgical approach among the nonsurgical group . Etiologic, diagnostic, and microbiologic factors were examined to develop an approach to antimicrobial therapy.

Semin Hematol, 1975 Apr, 12(2), 117 - 42
Antimicrobial mechanisms in neutrophilic polymorphonuclear leukocytes; Klebanoff SJ; Microorganisms ingested by PMNs are exposed to a variety of antimicrobial systems . Together they comprise a formidable armamentarium, and few organisms survive . The predominant antimicrobial system would be expected to vary with the species, the availability of oxygen and the type of microorganism ingested . There is considerable evidence that the MPO-mediated antimicrobial system plays an important role in the destruction of certain microorganisms in most species; chicken heterophils, however, do not contain MPO,40 and some microorganisms are resistant to this system due to the nature of their cell wall material.146 Further, microbial catalase may offer some protection . The granulocytes of some species (e.g., rabbit, chicken) are rich in cationic proteins and these agents may play a particularly important role in these cells . Granular cationic proteins are less plentiful in human cells.111 Organisms vary in their susceptibility to lysozyme and this enzyme is absent from bovine leukocytes.113 It is probable that the total microbicidal potential of the leukocyte is in excess of its needs under most circumstances . This "overkill" capacity is a reflection of both the level of activity of individual systems and their variety . Particular organisms are susceptible to more than one antimicrobial system and thus may be effectively handled by back-up systems when one is absent . Thus, an organism normally killed by the peroxidase system may be handled less efficiently but adequately when MPO is absent by other oxygen-dependent antimicrobial systems . When a defect in oxidative metabolixm is present as in CGD, both MPO-catalyzed and nonenzymatic oxygen-dependent systems are absent . The ingested organism can, in some instances, supply the needed product of oxidative metabolism (i.e., H2O2); in other instances, oxygen-independent antimicrobial systems are adequate to prevent microbial growth . However, in yet other instances, the organisms survive and multiply and severe infection results.

Am J Hosp Pharm, 1975 Apr, 32(4), 381 - 4
Particulate matter in reconstituted amphotericin B and assay of filtered solutions of amphotericin B; Piecoro JJ et al.; Amphotericin B colloidal solutions were prepared according to the manufacturer's directions and filtered with membrane filters of different porosity to test for particulate matter; and the concentration and in vitro microbiological activity of filtered and nonfiltered solutions were determined . The amphotericin B solutions contained numerous particles . Filtration through 0.85- and 0.45-mum filters did not reduce the in vitro antimicrobial activity, and filtration through 5-, 0.45-, and 0.22-mum filters did not alter the concentration of the drug when assayed spectrophotometrically.

Scand J Haematol, 1975 Apr, 14(2), 91 - 107
Vitamin B12-binding proteins of r-type, cobalophilin; Stenman UH; A gradient was developed for isoelectric focusing in the pH range 2-5 . Cobalophilin (earlier called R proteins or vitamin B12-binding proteins of R-type) was isolated from saliva and amniotic fluid in homogeneous form . It was found to be a glycoprotein with a molecular weight of 59,300-69,100 . The preparation from amniotic fluid contained 33% carbohydrate . Cobalophilin variants in plasma, serum, granulocytes, platelets, amniotic fluid, milk, saliva and gastric juice were characterized by isoelectric focusing . Most fluids and cells contained the same isoproteins, with pI values between 2.3 and 5.0 . Isoproteins of presumably myelogenic origin (e.g . those in granulocytes and plasma) had pI values below 4.2, whereas those of glandular origin (in milk and saliva) had a pI range of 4.0-5.0 . Serum contained more cobalophilin than plasma, owing to release of this protein from granulocytes during clotting . This phenomenon also changed the isoprotein pattern . Plasma and serum from newborn infants and from patients with leucocytosis, polycythaemia vera and chronic myelogenous leukaemia contained the same isoproteins as were found in plasma from healthy subjects . In addition to these, isoproteins with lower than 'normal' pI values were often found in chronic myelogenous leukaemia and occasionally in leucocytosis . It is concluded that cobalophilin from different fluids and cells is a single microheterogeneous protein with a variable carbohydrate composition . The distribution of cobalophilin in different body fluids and cells supports the suggestion that cobalophilin is an antimicrobial protein (Gullberg 1972) like lactoferrin and lysozyme.

Isr J Med Sci, 1975 Apr, 11(4), 322 - 34
Antimicrobial therapy in patients hospitalized in a medical ward . A report from the Boston Collaborative Drug Surveillance Program; Levy M et al.; The pattern of use of antimicrobial agents in 1,700 patients hospitalized in a medical ward at the Hadassah University Hospital, Jerusalem, during 1969--72, is analyzed . Penicillins comprised 56%, tetracyclines 11%, streptomycin 9% and cephalosporins 3% of the total antimicrobial exposures . Ampicillin was given to 20% of the patient population . The use of tetracyclines and chloramphenicol fell steadily from 1969 to 1972 . Fifty-five percent of the recipients of antimicrobial drugs received only one agent, 19% had concomitant therapy with several agents and the remainder received multiple antimicrobial drugs sequentially . One hundred and ten patients (6.5%) developed adverse reactions; the most common being rash and gastrointestinal reactions . Only two of the reactions were classified as causing major morbidity.

Ann Intern Med, 1975 Mar, 82(3), 367 - 71
Adult toxoplasmosis presenting as polymyositis and cerebellar ataxia; Greenlee JE et al.; A patient with toxoplasmosis had cerebellar, spinal cord, nerve root, and skeletal muscle symptoms . Toxoplasma gondii was isolated from skeletal muscle, and toxoplasma antibody titers were persistently elevated . The disease has been recurrent during a 3-year period with only temporary response to specific antimicrobial therapy.

J Pharm Sci, 1975 Mar, 64(3), 420 - 4
Microbiological determination of drug partitioning . IV . Drug-protein interactions; Javidan S et al.; The protein binding characteristics of chloramphenicol, furazolium chloride, benzalkonium chloride, and phenylmercuric nitrate were described from their partitioning behavior in gelatin-acacia complex coacervate systems . Although the partitioning was determined by two different methods (microbiological and chemical), the microbiological method was more reliable for this type of investigation . Drug-protein parameters were calculated for the four antimicrobials . The advantages of the coacervate systems over other models for protein binding studies of drugs are discussed.

Lloydia, 1975 Mar-Apr, 38(2), 117 - 24
Antimicrobial agents from higher plants . The antimicrobially inactive components of Ptelea trifoliata L; Mitscher LA et al.; From the weakly antibacterial non-quaternary alkaloidal fractions from Ptelea trifoliata L . (Rutaceae), ten tertiary quinol-2-one and quinol-4-one alkaloids were isolated and identified . In addition, beta-sitosterol, beta-sitosteryl-beta-D-glucoside and bergapten were isolated . None of these compounds possessed perceptible antimicrobial activity . The weak antimicrobial activity of the neutral and alkaloidal fractions was traced to small amounts of pteleatinium chloride which had not been completely separated by bulk processes . Alkaloids previously known to be present in P . trifoliata which were found in this study ptelefoline methyl ether, pteleine and skimmianine . Alkaloids previously known but new to this plant were lunidoine and isomaculasidine . Alkaloids newly found in nature were neohydroxylunine, hydroxylunidonine, 6-methoxylunidoine, 6-methoxylunineand 6-methoxy-hydroxylunidine . The structure of the latter three bases is proposed tentatively.

Schweiz Med Wochenschr, 1975 Mar 1, 105(9), 277 - 82
{Selection of drugs in chemotherapy}; Keller H; An attempt has been made to classify the wide range of available antimicrobial chemotherapeutic agents from the practical viewpoint . A group of drugs with selective indications and a series of alternative chemotherapeutic agents are distinguished from chemotherapeutic agents for everyday medical routine (penicillin G and analogs, ampicillin, tetracyclines, sulfonamides) . The indications for the main drugs and some practical guidelines for chemotherapy are summarized . The excessive commercial supply of ampicillin derivatives and cephalosporins comes in for special comment . It is emphasized that some valuable antibiotics (cephalosporins, carbenicillin, gentamycin, kanamycin) should be kept in reserve.

Lloydia, 1975 Mar-Apr, 38(2), 109 - 16
Antimicrobial agents from higher plants . The quaternary alkaloids of Ptelea trifoliata; Mitscher LA et al.; Quaternary alkaloid extracts of Ptelea trifoliata showed potentially interesting antimicrobial activity . Chromatographic examination showed the presence of six components . Of these, choline and O-4-methyl ptelefolinium were known compounds . Rational structures are proposed for the new alkaloids, O-4-methylhydroxyluninium, neohydroxylunine and pteleatinium salts . Pteleatinium salt is responsible for the antimicrobial activity of the extracts of the plant.

J Med Chem, 1975 Mar, 18(3), 312 - 4
Synthesis and antitrichomonal activity of certain pyrazolo (1,5-a) pyrimidines; Senga K et al.; Several bridgehead nitrogen heterocycles were synthesized to be screened as antimicrobial agents, modeled after nalidixic acid . The activity of these new compounds, all derivatives of 3-nitro-4,6-disubstituted pyrazolo (1,5-a)pyrimidin-7-ones (3,7,8, and 9), however, was found to be highly specific for Trichomonas foetus and completely lacking in activity against bacteria, fungi, and parasites other than Trichomonas . Of the nine componds synthesized, including the intermediate 4,6-disubstituted pyrazolo (1,5-a) pyrimidin-7-ones (2-6) and the 6-substituted or unsubstituted pyrazolo (1,5-a) pyrimidin-7-ones (1 and 4), only 6-carbethoxy-4-ethyl-3-nitropyrazolo(1,5-a)pyrimidin-7-one (7) was found to be a potent antitrichomal agent, being comparable or perhaps better than metronidazole . From a tentative structure-activity relationship study, it was apparent that the combination of the 3-mitro, 4-ethyl, and 6-carbethoxy groups imparted specific activity, wheras other substitutions imparted little or no antitrichomonal activity.

Am J Dis Child, 1975 Mar, 129(3), 328 - 30
Susceptibilities of bacteria to different antibiotic regimens . Study in two nursery populations; Dery P et al.; Hospital nursery A has used chloramphenicol and nursery B has used the combination of penicillin G sodium and kanamycin sulfate routinely in the treatment of neonatal sepsis and other bacterial infections . A hypothesis was formulated that these different antibiotic pressures would select out a substantial number of populations of resistant bacteria in each of the two nurseries . This was tested by periodic sampling of the skin, mouth, and rectal flora of babies and the permanent personnel in these nurseries . These bacteria were studied for susceptibility to a number of antibiotics . The population of resistant strains selected out was correlated with the antibiotics used in each nursery . There is a need for continuing surveillance of hospital nursery strains of bacteria for in vitro susceptibilities to commonly prescribed antimicrobials.

Clin Obstet Gynecol, 1975 Mar, 18(1), 243 - 53
Role of preventive methods in the control of venereal disease; Hart G; PIP: The role of prophylactic techniques in controlling venereal disease (VD) continues to be disputed despite the fact that prophylactic techniques have been used for centuries . Focus in this discussion is on the effectiveness of available prophylactic methods and some factors influencing the impact of effective prophylaxis on disease control . For practical purposes there are 3 categories of personal prophylaxis: mechanical (of which the condom is most important), locally acting measures, and systemic chemotherapy . Fallopio reported in the 16th century the 1st use of the condom to protect 1100 men from syphilis . Since then the condom has been an important element of many control programs . Condoms should be undamaged, of good quality, and used at the right time in the correct manner . Frequently the condom fails to prevent VD because of deficiencies in these conditions . Several studies have suggested that the condom may be of prophylactic value: venereal infection was detected in 9.5% of those using a condom or early treatment, but in 22% of those using inadequate prophylaxis and in 68.5% of those using none . There is inadequate evidence to support the effectiveness of available local acting prophylactic agents . Systemic antibiotics offer an effective form of prophylaxis . In addition, due to their potent specific antimicrobial properties, systemic antibiotics offer the unique advantage of aborting infection when administered a considerable time after exposure . A recent study demonstrated that 200 mgm minocycline, given as a postexposure prophylactic, decreased the attack rate of gonococcal urethritis by 55%, but those patients developed infection experienced a prolonged incubation period and tended to be infected with relatively resistant strains . These findings suggest the possibility of a more serious sequel: production of a chronic asymptomatic carrier state . Abortive VD therapy in managing a rape victim requires special consideration . Assessment of management should be based on the following: the likelihood of infection, the risks of treatment, the efficacy of treatment, and patient follow-up . Even when safe and effective techniques are available, their impact on VD control may be minimal if they are only rarely used . In many environments condom use ranges 3-20% among VD clinic patients and rarely exceeds 25% in the general male population . Condoms are used least by those who need them most . If utilization is to be increased, the motives for not using condoms must be understood . The primary objective in disease control is to reduce the reservoir of infected individuals while minimizing their contact with the uninfected population .

Clin Obstet Gynecol, 1975 Mar, 18(1), 143 - 51
Neonatal and childhood gonococcal infections; Israel KS et al.; Maternal, fetal, and neonatal morbidity and mortality can be significantly decreased by selective screening of prenatal patients for gonorrhea, early treatment, and follow-up cultures after treatment for gonorrhea . Ophthalmia is the most significant neonatal gonococcal infection . Administration of silver nitrate at delivery is the best prophylaxis against gonococcal ophthalmia . Treatment of gonococcal ophthalmia, however, requires parenteral penicillin, conjunctival antimicrobial therapy, and hospitalization . Treatment of the gonococci-infected mother is also indicated . Childhood gonorrhea is most commonly manifested as vulvovaginitis in girls or urethritis in boys, usually without associated disseminated gonococcal infection . Transmission can occur by indirect contact with an infected parent or involuntary or voluntary sexual activity: in children over age 10 years transmission of gonococci most commonly involves voluntary sexual activity . Emphasis should be placed on early treatment of the infected child, follow-up cultures, and contact tracing . Diagnosis of gonococcal infection requires adequate specimens, gram stains, and cultures for N . gonorrhoeae . In disseminated neonatal gonococcal disease, gram strains and cultures of the conjunctiva, oropharynx, orogastric aspirates, anogenital area, umbilicus, and external ear canal frequently aid in the diagnosis . Frequently, a gram strain of the urethral discharge in boys is sufficient for diagnosis of gonorrhea; in girls cultures are necessary . Since the incidence of gonorrhea in children has increased, the importance of epidemiologic analysis and follow-up after treatment can not be overemphasized.

Am J Trop Med Hyg, 1975 Mar, 24(2), 320 - 5
Attempted prevention of diarrheal disease in Apache children with a non-absorbable broad-spectrum antimicrobial; Hirschhorn N et al.; A double-blind study was conducted to test the prophylactic effect of a non-absorbable broad-spectrum antimicrobial (oral colistin sulfate) against acute diarrhea in Apache children . Children 1 to 6 months old had over twice the morbidity from diarrhea if assigned to the antimicrobial group as compared to placebo, while the toddler group (7-30 months) taking the antimicrobial had somewhat less diarrhea . Enteropathogenic E . coli were significantly more often isolated from the antimicrobial group (but only in well children) . No special effect on the children's growth by the antimicrobial was discerned.

Clin Obstet Gynecol, 1975 Mar, 18(1), 35 - 56
Acute pelvic inflammatory disease: current concepts of pathogenesis, etiology, and management; Eschenbach DA et al.; In summary, acute salpingitis is an extremely common disease with much morbidity and is undoubtedly increasing in incidence as a result of the increasing incidence of gonorrhea; the increasing use of the IUD as a means of fertility control almost certainly also contributes to the problem . It is remarkable that research concerning the pathogenesis, etiology, diagnosis, and treatment of salpingitis has been all but nonexistent in the United States until recently . We believe that evidence implicating IUD usage in salpingitis now makes it obligatory that individuals involved in family planning research determine the actual morbidity associated with IUD usage . Prospective cohort studies comparing the subsequent morbidity in patients randomly assigned to IUD versus other contraceptive methods are long overdue . The morbidity due to salpingitis associated with specific types of devices should also be compared . Other factors responsible for the breakdown in local antimicrobial defense mechanisms in women who develop salpingitis require further study . Clinical gynecologists must determine in the future the optimal method for the treatment of nongonococcal salpingitis, for which no clear-cut therapeutic recommendations are available at the present time . Such therapeutic studies should be conducted in conjunction with innovative studies concerning the etiology of nongonoccal salpingitis . The need for removal of an IUD from patients with salpingitis should be determined . Public health officials appear to have largely ignored the problem of salpingitis in patients attending public VD clinics and have not been notably successful in making the public aware of the nature of the early manifestations of salpingitis, of the need to seek early treatment in order to preserve fertility, and of the need to treat sexual partners of women with gonococcal infections . Investigations of infectious diseases in general, and pelvic inflammatory disease in particular, must increasingly enter the mainstream of research in the future if this disease is to be effectively treated and/or prevented in gynecologic patients.

Clin Pharmacol Ther, 1975 Mar, 17(3), 355 - 62
Iodine absorption in burn patients treated topically with povidone-iodine; Lavelle KJ et al.; Providone-iodine is used as a topical antimicrobial in burn patients . Although absorption of iodine has been thought to be negligible, several patients have recently been noted with substantial elevations of serum free iodide . Unexplained abnormalities occurred in several of these patients, renal failure, metabolic acidosis, and elevation of serum glutamic oxaloacetic transaminase . It is conceivable that the large iodide loads noted were at least in part responsible for these abnormalities.

Farmaco {Sci}, 1975 Feb, 30(2), 137 - 46
Antimicrobial properties of some 3-acyl-4,7-disubstituted indoles; Malesani G et al.; In continuation of research on indole derivatives as potential chemotherapeutic agents, the antimicrobial properties of some 4,7-disubstituted 3-acylindoles were studied; the derivatives tested were 4,7-dimethoxy-, 4-hydroxy-7-methoxy-, 4,7-dihydroxyindoles and indole 4,7-quinones . Only the dihydroxy compounds (V a-c) proved active against certain bacterial strains . In order to test whether the action mechanism was analogous to that of mitomycin, a series of experiments was carried out to study the formation of complexes with DNA . It was found that only the substances with antimicrobial activity can form complexes, and it is therefore suggested that the action mechanism involves interference with cellular DNA.

Fed Proc, 1975 Feb, 34(2), 202 - 4
Clinical implications of the presence of drug residues in food; Hewitt WL; Untoward clinical effects in man of drugs or chemicals as food residues might occur from direct pharmacological action, stimulation of hypersensitivity, or effects on cell regulatory processes . Antimicrobial residues might also influence the normal bacterial microflora of the skin, mucous membranes, and gastromintestinal tract . No direct evidence exists to incriminate antimicrobial drug food residues in any of these events . The permissible residues of antimicrobial substances are so low and the assay procedures for detecting them so sensitive that adequate surveillance should preclude harmful effects in man from these agents . Problems still remain with respect to potential carcinogenicity of drugs and chemicals as food residues.

Fed Proc, 1975 Feb, 34(2), 197 - 201
Drug and chemical residues in domestic animals; Mussman HC; Given the large number of chemical substances that may find their way into the food supply, a system is needed to monitor their presence . The U . S . Department of Agriculture's Meat and Poultry Inspection Program routinely tests for chemical residues in animals coming to slaughter . Pesticides, heavy metals, growth promotants (hormones and hormonelike agents), and antibiotics are included . Samples are taken statistically so that inferences as to national incidence of residues can be drawn . When a problem is identified, a more selective sampling is designed to help follow up on the initial regulatory action . In testing for pesticides, only DDT and dieldrin are found with any frequency and their levels are decreasing; violative residues of any chlorinated hydrocarbon are generally a result of an industrial accident rather than agricultural usage . Analyses for heavy metals have revealed detectable levels of mercury, lead, and others, but none at levels that are considered a health hazard . Of the hormone or hormonelike substances, only diethylstilbestrol has been a residue problem and its future is uncertain . The most extensive monitoring for veterinary drugs is on the antimicrobials, including sulfonamides, streptomycin, and the tetracycline group of antibiotics that constitute the bulk of the violations; their simultaneous use prophylactically and therapeutically has contributed to the problem in certain cases . A strong, well-designed user education program on proper application of pesticides, chemicals, and veterinary drugs appears to be one method of reducing the incidence of unwanted residues.

J Antibiot (Tokyo), 1975 Feb, 28(2), 118 - 21
Lysocellin, a new polyether antibiotic . I . Isolation, purification, physico-chemical and biological properties; Ebata E et al.; A new antibiotic, lysocellin (K-5610), WAS ISOLATED FROM Streptomyces cacaoi var . asoensis K-9 Met- . Lysocellin was obtained as a colorless crystalline needles from both the cultural filtrate and the mycelium of the organism . The antibiotic melted at 158 similar to 160 degrees C and had a molecular formula C34H59O10Na-1/2H2O . It had antimicrobial activity against gram-positive bacteria, antibiotic-resistant Staphyloccus aureus and some fungi, but not against gram-negative bacteria . Based on its physico-chemical and biological properties lysocellin was identified as a new polyether antibiotic.

Mayo Clin Proc, 1975 Feb, 50(2), 91 - 8
Blood cultures: principles and techniques; Washington JA 2nd; Detecting the presence of microorganisms in blood is an important function of the clinical microbiology laboratory . With prompt isolation, identification, and antimicrobial susceptibility testing of bacterial isolates, the clinician can modify the selection and dosage of the antimicrobics used initially to treat a suspected septicemia . Principles and techniques for blood collection, culture, examination, and reporting are reviewed.

Fed Proc, 1975 Feb, 34(2), 205 - 8
Indirect consequences of low-level use of antimicrobial agents in animal feeds; Walton JR; Antibiotics may be classified as "therapeutic" or "feed" depending on their use for treatment of disease or for promotion of growth in animals . The mechanism of growth promotion is largely unknown, but it has been shown that the specific feed additive causes defined lesions in the cell wall of Escherichia coli . This effect may sensitize the bacteria to the action of therapeutic drugs . Damage to the bacterial cell wall may also cause the bacteria to be more susceptible to the body defense mechanisms . One form of stress may be defined in terms of a disturbance of intestinal flora brought on by relocation, group mixing, change of diet, or travel . Prolonged feeding of antimicrobial agents to animals has not been shown to be responsible for the current high level of R factors in the intestinal tract of man.

Pharmazie, 1975 Feb, 30(2), 109 - 11
Isolation and structure assignment of an antimicrobial principle from the volatile oil of Nigella sativa L . seeds; El-Fatatry HM; Refrigeration of the volatile oil of Nigella sativa L . seeds eventuates in a crystalline substance . The chemical structure of the compound was drawn from its chemical behaviour, as well as from its UV, IR, PMR and mass spectral data . The compound was found to be thymohydroquinone: confirmation of the structure was established via the preparation of its corresponding diacetate ester . The compound was found to have high antimicrobial effect against gram positive microorganisms

Thorax, 1975 Feb, 30(1), 72 - 9
Soluble proteins of bronchopulmonary secretions from patients with cystic fibrosis, asthma, and bronchitis; Brogan TD et al.; The concentrations of nine plasma proteins were determined by quantitative immunoelectrophoresis in sputum specimens from 29 patients with cystic fibrosis (CF) and from 24 patients with severe asthma and chronic bronchitis . The results suggested that the population of CF patients could be divided into two groups in spite of an absence of difference in clinical status between the groups . Average concentrations of seven plasma proteins in sputum of group I CF patients were identical with those in sputum of patients with bronchitis, but the average concentrations of six of these proteins in sputum from group II CF patients were higher than those in specimens from the bronchitic patients and were similar to corresponding concentrations in sputum from patients with asthma, all of whom were examined while in status asthmaticus . The average concentrations of 14 secretory proteins were the same in all sputum specimens whether or not they were produced by patients with cystic fibrosis, asthma or bronchitis . It was concluded that the concentrations in the bronchopulmonary secretions of proteins associated with host defence were not diminished in patients with cystic fibrosis, and failure to produce adequate concentrations of proteins with antimicrobial activity was unlikely to be responsible for the above average susceptibility to chest infection in cystic fibrosis . It is suggested that there exists a group of CF patients in whom a pulmonary allergic reaction generates an inflammatory response as severe as that characterizing status asthmaticus and that this response could be detrimental.

Med Cutan Ibero Lat Am, 1975, 3(5), 393 - 7
{Clinical and experimental study on an anti-inflammatory preparation of topical use . The 10-undecentil-l-ll pseudothiourea (AHR-1911)}; Ercoli N; Our previous studies led to the development of a drug, 10-undecen-1- pseudothiourea iodide (AHR-1911), with the characteristics of a broad spectrum of antibacterial-antimycotic action and anti-inflammatory properties in experimental lesions induced by burns, dextran, albumin, carrageenin and kaolin . Using different vehicles for topical use, these two types of therapeutic property were separated, yielding two pharmaceutical preparations with different indications . One is a 0,25% AHR-1911 preparation in a polyoxyethyleneglycol base, which in in vivo experiments has the antimicrobial efficacy of gentamycin ointment; the other, containing 10% AHR-1911 in a vanishing cream base with triethanolamine stearate, possesses the anti-inflammatory efficacy of the newer topical steroid preparations . The clinical data for this latter preparation agree with the experimental findings . Its activity in clinical conditions was found first by Di Prisco in dermatological cases and confirmed in contact dermatitis patients by Riobueno . Its usefulness in burns and contusions with excoriations, without a single instance of secondary infection was reported by Rojas Mratinez; its effectiveness in bursitis and tenosynovitis may extend its field of application beyond that of dermatology . Particularly impressive were the good results obtained in insect bites, due possibly to the antihistaminic effect of the drug acting synergistically with the anti-inflammatory one . In the experience of all the clinicians the preparation was very well tolerated.

Polim Med, 1975, 5(2), 163 - 6
{Prophylaxis of influenza with a clathrate of polyvinyl alcohol with iodine and boric acid}; Drobinski T et al.; Taking advantage of the viricdal and antimicrobial properties of the clathrate of polyvinyl alcohol with iodine and boric acid (PVAIB) and taking into account successful results obtained during the action in 1969, it was used again as a preventive measure during the epidemy of influenza in Poznan at the turn of 1971/1972 . In this period, the prophylactic action included 1477 persons who recieved the drug as nasal drops in 30 gram bottles . After the extinction of influenza we checked 459 persons who had taken the drug regularly, according to medical prescription . Out of this group, only 23 persons or 5% fell ill with influenza . If compared with general morbidity, this rate proved to be four times smaller.

Arch Exp Veterinarmed, 1975, 29(4), 621 - 9
{Relationships between chemical constitution and germicidial effect . 28 . Preparation, antimicrobial and anthelminthic effect of diiosothiocyanates}; Teubner H et al.; In comparison with monoisothiocyanates, diisothiocyanates were either less active or of the same activity against bacteria and fungi . None of the compounds tested possessed antimicrobial activity worth investigating further . However, compound No . 2 (2,4-diisothiocyanatomethyl ethoxybenzol) and compound No . 5 (1,3-dimethyl-4,6-diisothiocyanatomethylbenzol) were more active as anthelmintics against Enchytraeus than the p-phenylene diisothiocyanates.

J Clin Microbiol, 1975 Jan, 1(1), 37 - 43
Practical aerobic membrane filtration blood culture technique: clinical blood culture trial; Sullivan NM et al.; During the course of preliminary clinical trials of an improved membrane filter blood culture system, filter plugging produced by a gelling of the lysing solution was observed when the patients had high leukocyte counts . A solution of streptokinase-streptodornase (Varidase, Lederle Laboratories) dissolved or prevented the gel and permitted rapid filtration without plugging . With streptokinase-streptodornase incorporated in the filtration procedure, a comparison of several culture systems was carried out on 176 blood cultures . Brucella broth with and without sodium polyanethol sulfonate, a prereduced osmotically stabilized broth, pour plates, and an improved aerobic membrane filter system were compared . The membrane filter system yielded 29 of the total of 37 positive cultures, far surpassing all other systems . Eight of these cultures were detected first by the filter technique, and 13 were positive only in this system . Nineteen of the 37 positive cultures were from patients on antimicrobial agents . Fourteen of these were detected by the filter, twice the number detected by any of the other systems.

Chemotherapy, 1975, 21(2), 61 - 6
In vitro study on the effects of silver sulfadiazine on bilirubin binding; Speck WT et al.; Silver sulfadiazine is a new topical antimicrobial agent with a broad spectrum of activity against most bacterial (both gram-positive and gram-negative) and many fungal species . This broad spectrum of activity suggests that silver sulfiazine may be useful in clinical situations which require the inhibition of cutaneous bacterial and/or fungal colonization . The present study was undertaken to determine the effect of this agent on a bilirubin-protein binding . Using chromatographic procedures on artificially jaundiced sera and human serum albumin solutions, we were unable to detect any releast of protein-bound bilirubin by a saturated suspension of silver sulfadiazine.

Chemotherapy, 1975, 21(5), 265 - 80
Model of the antimicrobial silver uracil; Wysor MS; A model is proposed for the antimicrobial agent, silver uracil, whereby silver interacts with uracil forming a silver uracil combination with the silver in the +1 state intercalating between stacked uracils in a manner similar to a 'sandwich' model . The uracils maintain stability by hydrogen bonding with the water solvent, and 'flip-flop' through an antiparallism mode at 220 degrees . The silver bonds to the uracil by a charge transfer mechanism, increasing the nuclear shielding field of the pyrimidine . The presence of the water (solvent) is necessary for the structure.

Birth Defects Orig Artic Ser, 1975, 11(1), 73 - 6
Chorioretinal lesions, sea-blue histiocytes and other manifestations in familial chronic granulomatous disease; Lischner HW et al.; Several little-emphasized manifestations of familial chronic granulomatous disease are considered: destructive chorioretinal lesions may be as constant as the pigmented histiocytosis seen in reticuloendothelial organs and could be related to a defect in the phagocytic activity of the retinal pigment epithelium; pigmented histiocytes with the staining characteristics of sea-blue histiocytes may be present in the bone marrow; patients may present with lesions resembling eosinophilic granuloma . Also discussed are some observations related to the sequestration of bacteria within phagocytic cells and the use of continuous antimicrobial therapy.

Geburtshilfe Frauenheilkd, 1975 Jan, 35(1), 24 - 7
{The serum and uterine muscle concentrations of Cephradin and Cephalothin}; Michel CF et al.; On the day of operation 2 grams of Cephradin was given intravenously to 33 patient and 2 grams of Cephalothin was given intravenously to 31 patients . At various time intervals, uterine tissue and serum was removed . The mean serum concentrations of Cephradin were 3 times higher and the mean tissue concentrations of Cephradin were 7-8 times higher than the corresponding concentrations of Cephalothin . Because of the difference in protein binding of the examined cephalosporins (Cephradin 6%, Cephalothin 60-65%) the difference for the antimicrobially active portion (Protein free portion) is even more favorable for Cephradin . The significance of these pharmacokinetic differences for the treatment are obvious.

Res Commun Chem Pathol Pharmacol, 1975 Jan, 10(1), 173 - 6
Structure-activity relationships for antimicrobial cephalosporins; Tinland B; The antimicrobial activity of a series of 7-mandelamido-3-cephem-4-carboxylic acids was studied using the Free-Wilson method . Electron-withdrawing and lipophilic properties of the substituents are shown to play an important role in the activity.

Monatsschr Kinderheilkd, 1975 Jan, 123(1), 15 - 6
{Drug therapy in newborns and young babies}; Gladtke E; Over the last twenty years drug therapy for the newborn and young infant has developed from its empirical origins to a state where the results of intensive research can be applied . As biochemical studies have shown, enzyme activities and the mechanisms of detoxification are dependent on age . These findings have prompted pharmacokinetic considerations with regard to dosage, especially in repetitive dosage regimens . Further aspects include interference and in particular the protein-binding of drugs in the newborn, side effects of drugs administered to the expectant mother, only seen later in their infants, and side effects characteristic for the newborn . Finally mention is made of some recent advances in pediatric antimicrobial therapy . The most frequent side effect is the inefficiency of drugs because of underdosage.

Farmaco {Sci}, 1975 Jan, 30(1), 8 - 19
{Salts and betaines with quaternary ammonium function derived from sulfanilamide and from p-aminobenzoic and p-aminosalicylic acids}; Casini G et al.; The preparation of quaternary ammonium derivatives of sulfanilamide and of tertiary amines containing an aliphatic chain up to c-18 is described . Some members of this series show greater antimicrobial activity than the parent substances . This is found also in comparison with other analogous series which have been prepared.

Pharmacol Ther Dent, 1975, 2(1), 1 - 11
An in vivo study of an antimicrobial mouth rinse on supragingival and subgingival plaque and calculus formation; Rokita JR et al.; An antibiotic mouth rinse (CC10232) was used twice a day for one week in human subjects in a supervised double blind clinical and histological study . Nylon strips were placed supra and subgingivally for one week and then sectioned, stained and examined . Results showed that the rinse containing CC-10232 reduced the amount of plaque and reduced the amount of mineralization in 4 of 5 subjects.Also, no spirochetes were found in subjects who utilized this rinse.

Am J Clin Pathol, 1975 Jan, 63(1), 149 - 52
Comparison of isotonic and radiometric-hypertonic cultures for the recovery of organisms from cerebrospinal, pleural and synovial fluids; Rosner R; Two hundred eighteen (218) specimens of body fluids were examined by both isotonic and hypertonic culture methods . The specimens examined included 108 pleural fluids, 43 synovial fluids, and 67 cerebrospinal fluids . Organisms were recovered in 99 instances by means of the isotonic system and in 140 instances by the hypertonic system . The hypertonic system also involved the use of radiometric assay for the detection of positive cultures . In all 140 cases, detection was accomplished within 36 hours after collection of the specimen by the radiometric method, while only 26 specimens showed any visual evidence of bacterial growth . Of the 218 patients involved, 198 were receiving antimicrobial therapy in which the antimicrobial agent attacked the bacterial cell wall.

Z Allg Mikrobiol, 1975, 15(7), 495 - 503
Leukaemomycin, an antibiotic with antitumor activity . I . Screening, fermentation, and biological activity; Fleck W et al.; A Streptomyces strain belonging to S . griseus (Krainski) Waksman et Henrici 1948 sensu Hutter (1967) was found to produce an antibiotic designated as leukaemomycin . The red-pigment antibiotic, having antimicrobial and antitumor activity in vitro and in vivo, was isolated from C-, N-, and Fe-containing cultures of the strains IMET JA 3933, IMET JA 5570, IMET JA 10086, and IMET JA 10431 . Leukaemomycin has indicator properties and is produced by the classic procedures of submerged fermentation . The crude base of leukaemomycin consists of 4 main components, designated as leukaemomycin A, B, C, and D . The biological activity of the main components leukaemomycin B and C was compared . The biological activity and the physicochemical properties of leukaemomycin C are identical with known properties of the anthracycline antibiotic daunorubicin.

J Biomed Mater Res, 1975 Jan, 9(1), 55 - 68
Antimicrobial polymers; Ackart WB et al.; A number of carboxyl-containing ethylene copolymers have been prepared which exhibit long term antibacterial and antifungal properties . These materials containing antimicrobial agents bound to the copolymer backbone as carboxylate salts, have been tested for their applicability to hospital products as a means of providing "self-sanitizing" articles . Tests have shown that these materials, although not bactericidal, do inhibit microbial growth . Investigations of the compatibility of these polymers with commodity polymers have been made and water emulsions of the polymers have been tested for applicability as components of product protectant coatings.

Vet Med (Praha), 1975, 20(1), 1 - 12
{Residues of antimicrobial substances in the meat and organs of slaughter calves}; Malikova M et al.; Using a modified Gartside diffusion method (1960) the incidence of the residues of antimicrobial substances was followed in two categories of calves commercially slaughtered at the Brno Slaughter House . For testing the following three collection strains were used: B . subtilis (ATCC 6633), B cereus, var . mycoides (ATCC 11778), Sarcina lutea (ATCC 9341) . In light weight calves samples of bile, liver, kidney, diaphragmatic and hind limb muscles, in heavy calves, due to technical reasons, only bile, liver and diaphragmatic muscle samples were examined . Residues were demonstrated in 26.2% of 103 light (suckling) calves; the most frequent finding was in the bile (22.2%) and kidney (15.5%) . Identical residue findings in the diaphragmatic muscles and in the skeletal muscles of the hind extremities in light calves correspond to the formerly described results in calves from emergency slaughter (Malikova et al . 1974) . In heavy calves the residues were demonstrated in 41.7% of 156 examined; the most frequent finding was in the liver (42.3%) and in the diphragmatic muscles (34%) . Under the present operation conditions of calf fattening using milk replacer Biosan 20 not even an interval of 17-20 hours between the last feeding and the slaughter proved sufficient for elimination of the antimicrobial substances from the bodies of the slaughter animals.

J Hyg Epidemiol Microbiol Immunol, 1975, 19(1), 72 - 8
Bioautographic characterization of antimicrobial substances after electrophoresis in agar gel; Porres JM; Bioautography following electrophoresis on agar gel, a technique for the characterization of antibiotics, is described in detail and its possible uses and advantages discussed . Eleven antibiotics of the beta-lactamic group were characterized . Penicillin G and Penicillin V showed two components with anti-microbial activity . Attempts were made to identify the components by an adaptation of the technique and the results are discussed.

Farmaco {Sci}, 1975 Jan, 30(1), 70 - 80
{Synthesis and antibacterial activity of N-(benzothiazolyl-2-carbonyl)-N-1-(2-thiazolyl)hydrazine}; Russo F et al.; The synthesis and chemical behaviour of N-(benzothiazolyl-2-carbonyl)-N-1-(2-thiazolyl)hydrazines is described . All the products were screened in vitro for antimicrobial activity . Some of them were found to give positive results.

Drugs, 1975, 10(2), 81 - 111
Antibacterial Drugs today: II; Ball AP et al.; Since the development of the sulphonamides in the 1930s and the subsequent development of antibiotics from the 1940s onwards, there have now been many drugs developed which are capable of chemotherapeutic activity in a patient infected by a susceptible micro-organism . This review is concerned with precise descriptions of important groups of antimicrobial drugs, with emphasis being placed on the more recently developed drugs . With each group of drugs the pharmacology, major therapeutic indications, dosages and adverse reactions are discussed . Part II of the review discusses the cephalosporins, polymyxins and aminoglycosides . The place of each in therapy is defined.

Acta Microbiol Acad Sci Hung, 1975, 22(3), 271 - 4
Post-therapeutic levels of antimicrobial drugs in faeces; Bognar S et al.; After oral administration for 3 days, furazolidone disappeared from the faeces on the first, polymyxin B and ampicillin on the fourth, and trimethoprim + sulphamethoxazole and nalidixic acid on the fifth day.

Rev Inst Antibiot (Recife), 1974 Dec, 14(1-2), 83 - 9
{Antimicrobial substances of superior plants . 44 . Isolation of diterpene acid from Croton aff . argyrophylloides Muell arg . (Euphorbiaceae)}; De Albuquerque MM et al.; In this paper the authors present the first report concerning the biological effects of a diterpene isolated from Croton aff . argyrophylloides Muell . Arg (Euphorbiaceae) . Some biological and physiochemical properties of the antibiotic, named argyrophillic acid, were appreciated in comparison with those presented by cunabic acid, an antibiotic isolated from Icthyothere cunabi . The authors still show the microbial action of the abietic acid and confront it with that of the argyrophilic acid, the new antibiotic here reported.

Rev Inst Antibiot (Recife), 1974 Dec, 14(1-2), 39 - 50
{O and C prenylated chalcones with antineoplastic and antibiotic activities isolated from Lonchocarpus neuroscapha Benth}; De Mello JF et al.; In the course of our program on the antimicrobial and antineoplastic substances from higher plants we have studied many flavonoid compounds isolated from root back of Lonchocarpus neuroscapha Benth . In the present paper a slight effect on sarcoma 180 and Ehrlich carcinoma of cordoin, 4-hydroxy-cordoin and 4-hydroxy-derricin, as well as the only observed effect of derricin on sarcoma 180 were observed . The antimicrobial action of four prenylated chalcones, i.e . 4-hydroxy-derricin, 4-hydroxy-lonchocarpin, 4-hydroxy-cordoin and 4-hydroxy-isocordoin is reported.

Rev Inst Antibiot (Recife), 1974 Dec, 14(1-2), 101 - 4
{Antimicrobial substances of superior plants . 45 . Primary observations of 2 new quinoids isolated from Hyptis fructicosa Salzm ex Benth(Labiatae)}; De Araujo MD et al.; The authors present the first observations on the isolation of two quinonoid compounds from Hyptis fructicosa Salzm ex Benth; Labiatae . The referred naturally compounds present antimicrobial and antineoplastic activity against Gram-positive microrganisms and mouse Erlich carcionama, respectivelly.

Paediatr Indones, 1965 Jan-Jun, 5(1-2), 652 - 5
Studies on infantile diarrhea; Chow HK et al.; PIP: Infantile diarrhea, the incidence of which is fairly common in Peking, has been studied there since 1957 . The etiology of the disease is explained in detail . It seems to occur all year round but more often in the summer months . Many of the strains of disease-causing bacteria are found to be resistant to the commonly used antimicrobial drugs . Fluid and electrolyte balance studies were conducted on infantile diarrhea patients . A combined therapy of good general management, proper feeding, prompt control of infection, and adequate fluid therapy seems to work best . Simple fluid therapy seems to be effective with most cases . Of the 200-400 cases treated since 1957 by the authors, the mortality rate has dropped substantially . Most patients, except those with serious complications, can be cured at present .

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