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| Scand J Infect Dis Suppl, 1978, (14), 279 - 84 Penetration of antibiotics into the normal and diseased maxillary sinus mucosa; Ekedahl C et al.; A micro-method was developed for determination of the concentrations of antibiotics in the mucous membranes of the maxillary sinus in man . At different times after the administration of antibiotics (potassium phenoxymethylpenicillin, lymecycline and bacampicillin) the concentration was determined in serum and in pieces of maxillary sinus mucosa obtained at operation . It was found that the concentrations in the mucosa varied within wide ranges during the first 60 minutes after the operation but in samples taken at 90 minutes the fluctuations between the individuals were within the standard error of the method . Concentrations well above the MIC values for the majority of bacterias found in sinusitis were registered in the peaks . Six hours after the administration considerable amounts of active antibiotics were still detected in the maxillary sinus mucosa. Can Med Assoc J, 1977 Nov 19, 117(10), 1159 - 61 Detection and prevalence of pneumococci with increased resistance to penicillin; Dixon JM et al.; Susceptibility to penicillin was determined for 6000 strains of pneumococci isolated during 1974--76 from patients in Alberta and the adjacent region of the Northwest Territories . Strains were considered to be relatively resistant if the minimum inhibitory concentration (MIC) of penicillin was 0.16 microgram (0.26 U)/mL or more, which is eight or more times greater than the MIC for fully susceptible strains . Resistance was detected in 143 strains (2.4%) isolated from 122 patients and belonging to four capsular types . The MIC of the most resistant strains was 0.32 microgram (0.53 U/mL . Penicillin-resistant strains were highly resistant to oxacillin, the MIC being at least 30 times greater than that for penicillin-susceptible strains . Pneumococci resistant to penicillin may readily be detected by the narrowness or absence of a zone of inhibition around a 1-microgram oxacillin disc in susceptibility tests on blood agar . The degree of resistance reported here is relative and does not necessarily preclude successful treatment with full therapeutic doses of penicillin G, but penicillin preparations that give low blood concentrations may not be suitable for treating infections caused by these strains. Pol J Pharmacol Pharm, 1977 Nov-Dec, 29(6), 663 - 73 Studies on pyrazine derivatives . Part VIII . Synthesis and tuberculostatic activity of some 6-alkylthio- and 6-phenylthiopyrazine-2-carboxylic acids; Foks H et al.; 2-Cyano-6-alkylthio- and 6-phenylthiopyrazines were prepared from 2-cyano-6-chloropyrazine (CCP) in the reaction with mercaptans . By the transformation of the -CN group the corresponding amides, thioamides, amidoximes, acids, esters and hydroxamic acids and hydrazides were obtained . The oxidation of sulfur in the above mentioned compounds led to sulfoxy- and sulfonyl derivatives . In the screening for antituberculous activity compounds 30 and 42 showed the greatest activity (MIC = 31.2 microgram/cm3) against H37Rv strain and compund 8 so did against saprophytic ATCC 607 strain . The compounds with 6-benzylthio grouping were more active against ethionamide, isoniazide and capreomycine resistant strains. Zentralbl Bakteriol {Orig A}, 1977 Nov, 239(3), 403 - 8 {In vitro and in vivo activity of tiamulin against leptospires (author's transl)}; Laber G et al.; The minimal growth inhibiting concentration of tiamulin, a derivative of the diterpen antibiotic pleuromutilin, was evaluated in vitro against 11 different serogroups of leptospira interrogans by twofold serial dilution technique, in comparison to tetracyclin, dihydrostreptomycin and tylosin . The range of the MIC values of tiamulin is between 0.07 and 2.5 microgram/ml and thus comparable to the activities of the standard antibiotics tested (see table 1) . The chemotherapeutic efficacy (ED50) of the compound was examined in two experimental leptospiral infections of the Syrian hamster, in comparison to tetracyclin . Both compounds were administered orally for 3 days . In the L . canicola infection, the ED50 values were 103.8 mg/kg and 306.3 mg/kg body-weight for tiamulin and tetracyclin, respectively . In the L . grippotyphosa infection, the ED50 values amounted to 35.16 and 277.5 mg/kg bodyweight for tiamulin and tetracyclin, respectively . Based on these values, tiamulin in comparison to tetracyclin showed 3-8 fold higher efficacy in vivo after oral administration. Med Klin, 1977 Oct 28, 72(43), 1808 - 13 {Cephradine in open heart serugery . Concentrations of cephradine in pericardial exudate and serum after cardiac surgery (author's transl)}; Adam D et al.; The diffusion of cephradine into the pericardial exudate was measured in 19 patients undergoing heart surgery . Every patient received 2 grams of cephradine (=30 mg/kg) during a 20 minute infusion period, before, during, and after the operation, and than at intervals of 6 hours, together 8 grams per day . The highest mean serum level, 10 minutes after the end of the first injection was 150 microgram/ml and after repeated dosages 102.5 microgram/ml, and at the end of the infusion interval 3.2 microgram/ml in the mean . At the time of opening the pericardium the concentration of the substance in the pericardial exudate, 15, 30, 45 and 60 minutes after finishing the first injection, varied from 4.1 to 38.6 microgram/ml in the average . The postoperative maximum levels were higher than 50 microgram/ml and 6 hours after the respective administrations the levels varied between 12.83 and 15.77 microgram/ml in each case . These high concentrations of cephradine in the pericardial exudate could not be attributed to seepage of blood into the pericardium.-At specific "check points" bacteriological materials were taken . Out of 1168 specimens only 6.7% were bacteriological positive . Drains in wounds, the pleura or the pericardium were sterile in most cases . Intravenous catheters were contaminated only in 1% . However the contamination rate rises with period of storage . The results show that cephradine exhibits good diffusion into the exudate of pericardium . With the chosen dosage the concentrations of the antibiotic in the pericardial exudate are higher than the MIC values of most pathogen bacteria. Scand J Respir Dis, 1977 Oct, 58(5), 241 - 6 Absorption of rifampicin in gastrectomized patients . Effect of meals; Hagelund CH et al.; Rifampicin absorption was studied in six gastrectomized and six non-gastrectomized tuberculous patients who had been on continuous rifampicin therapy for more than 4 weeks . A dose of 450 mg was given on two occasions, first immediately after breakfast and, 2 days later, 1 h before breakfast . In all the gastrectomized and control patients a serum level well above the MIC for M . tuberculosis (0.2-0.5 microgram/ml) was achieved irrespective of whether rifampicin was administered after the meal or during fasting . Gastrectomized patients tended to have more delayed serum concentration peaks postprandially than when fasting . The differences in absorption were not statistically significant, and the serum concentrations remained above the MIC for M . tuberculosis for similar lenghts of time . Individual serum concentrations varied greatly, and this variation may represent a greater problem in the routine monitoring of rifampicin serum levels than administration of the drug with food. N Z Med J, 1977 Jul 27, 86(592), 93 - 4 The susceptibility of New Zealand isolates of leptospira to three antibiotics; Cameron GL; The susceptibilities of 14 recent isolates of Leptospira to benzyl penicillin, tetracycline and minocycline, were tested . All strains were highly susceptible to penicillin . The minimum inhibitory concentrations (MIC) of the two tetracyclines were generally low, and no significant difference was found between them. J Clin Pathol, 1977 Jul, 30(7), 620 - 2 Novobiocin and the differentiation of peptococci and peptostreptococci; Wren MW et al.; Paper discs containing 5 microng of novobiocin were used as a presumptive test to differentiate peptococci and peptostreptococci . Zone diameters were measured and minimum inhibitory concentrations (MIC) of the antibiotic for each group were performed to ascertain the activity of the antibiotic against these genera . All strains of peptococci showed no zone of inhibition in the disc test together with an MIC of 25 microng/ml or greater . All strains of peptostreptococci showed zones of inhibition of at least 15 mm diameter together with an MIC of 1-6 microng/ml or less. Ann Intern Med, 1977 Jun, 86(6), 708 - 13 Antibiotic concentrations in ascitic fluid of patients with ascites and bacterial peritonitis; Gerding DN et al.; Thirty-six paired specimens of serum and ascitic fluid from 21 patients with peritonitis and ascites, most with sponetaneous bacterial peritonitis and alcoholic cirrhosis, were assayed for antibiotic content . Antibiotics assayed and number of determinations were gentamicin, 14; tobramycin, 7; ampicillin, 5; clindamycin, 3; penicillin G, 2; cephalothin, 2; chloramphenico, 2; and cefazolin, 1 . In 31 pared specimens the ascitic fluid antibiotic concentration was about one half or more of the simultaneous serum level and in 17 assays exceeded 90% of the serum level . All antibiotics studied penetrated ascitic fluid equally well . Clinical response to antibiotic therapy was good in 12 of 16 patients with culture-proven bacterial peritonitis . Antibiotic levels in ascitic fluid exceeded the minimal inhibitory concentration of the infecting organisms in all but one patient who responded . Direct intraperitoneal instillation of antibiotics does not appear to be necessary routinely; however, there may be an initial lag of several hours before antibiotic concentrations is ascites achieve therapeutic levels. Am J Med, 1977 Jun, 62(6), 949 - 53 Amikacin in the treatment of gram-negative pneumonia; Trenholme GM et al.; A clinical efficacy study of amikacin in the treatment of 15 adults with nonbacteremic, gram-negative bacillary pneumonia is presented . All patients had serious underlying illnesses (11 organic heart disease, five chronic obstructive pulmonary disease, one cancer); 11 had undergone major surgical procedures . All had required respiratory assistance during their hospitalization and all had recently received other antibiotics . Thirteen of 15 patients showed clinical improvement with amikacin therapy; the pathogen was also eradicated in 10 of the 13 . The mean minimum inhibitory concentration of amikacin for the 17 isolated pathogens was 3.13 microng/ml . The mean peak serum concentration of amikacin was 17.7 microng/ml . No evidence of ototoxicity or nephrotoxicity was seen . Seventy-three case reports submitted to the manufacturer by multiple investigators of patients with gram-negative pneumonia, treated with amikacin, are also reviewed . All isolated pathogens were sensitive to both amikacin and gentamicin . Fifty-four (74%) of these patients showed improvement with amikacin therapy. Pathol Biol (Paris), 1977 May, 25(5), 291 - 8 {Subinhibitory concentrations of antibiotics . Effects on morphology and growth (author's transl)}; Lorian V; Experiments with subinhibitory concentrations of antibiotics revealed certain effects that had not been observed at higher concentrations . Two different effects are described: morphological changer and inhibition of growth . The expression minimum antibiotic concentration (MAC) has been shown to be of both theoretical and practical value . It has served to make plain the differences between the effects of various antibodies that were not observed at the MIC . The ratio MAC/MIC could be be of importance to characterize the effect of antibiotics. Antibiotiki, 1977 May, 22(5), 455 - 7 {Action of tetracyclines on the pseudotuberculosis microbe in vitro experiments and their effectiveness in experimental pseudotuberculosis in white mice}; Rogozina MI et al.; 227 out of 228 strains of pseudotuberculosis microbes studied in vitro proved to be sensitive to tetracyclines . The MIC of tetracycline and morphocycline ranged within 0.25--25 gamma/ml . The MIC of chlortetracycline and oxytetracycline was somewhat lower, i . e . 1--50 gamma/ml . When administered intramuscularly all the tetracyclines had pronounced therapeutic effect in experiments with albino mice infected with the antibiotic sensitive strains of J . pseudotuberculosis . Chlortetracycline proved to be the most active drug in treatment of albino mice per os. Surgery, 1977 Apr, 81(4), 426 - 30 The influence of biliary disease on the excretion of cefazolin in human bile; McLeish AR et al.; Forty-five patients with varying biliary pathology were injected with one gram of intramuscular cefazolin sodium prior to surgery . Serum, gallbladder bile, and common duct bile levels were measured . The type of biliary disease did not influence serum levels (mean, 29 mug per milliliter) which reached a peak one hour after injection . Mean common duct bile levels were reduced from 52 mug per milliliter in nonjaundiced patients to 4 mug per milliliter in those with jaundice (p less than 0.001) . Patients with radiologically functioning gallbladders had significantly higher mean gallbladder bile levels (21 mug per milliliter; p less than 0.005) . Surprisingly, the mean gallbladder bile level in acute cholecystitis was 25 mug per milliliter . As the minimum inhibitory concentration of cefazolin for organisms commonly found in the bile is 0.5 to 6 mug per milliliter, we suggest that cefazolin sodium may be of value in the treatment of biliary disease, particularly acute cholecystitis. Acta Pathol Microbiol Scand {B}, 1977 Apr, 85(2), 161 - 6 Effects of ampicillin on intracellular levels of adenosine triphosphate in bacterial cultures related to antibiotic susceptibility; Thore A et al.; Short time effects of ampicillin on viability and levels of intracellular ATP were studied in bacterial cultures and a close relationship between intracellular ATP levels and viability was demonstrated . The connection between the effects observed and MIC values is discussed . The possibility of using the phenomenon for rapid antibioitc susceptibility testing was studied in clinical isolates incubated for 2 hours followed by luciferase assay of intracellular ATP . A positive correlation was demonstrated between ampicillin-induced decreases in intracellular ATP and inhibitory zone diameters, as measured by the agar diffusion technique. Int J Clin Pharmacol Biopharm, 1977 Mar, 15(3), 121 - 5 Computer-calculated kanamycin dosage regimen and monitoring; Ritschel WA et al.; The applicability of a computerized dosage regimen determination based on a recently developed method for drugs following the minimum inhibitory concentration pattern (bacteriostatic drugs) has been tested for kanamycin injected intramuscularly in 8 patients with varying degrees of renal impairment . The dosage regimens for maintaining a minimum therapeutic kanamycin concentration of 5.0 micron g/ml was determined with the Wang 700 C Computer . After the 1st, 2nd, 3rd, 6th, 9th, and 12th dosing interval blood samples were taken and the acual kanamycin serum concentrations determined . The expected multiple dose serum level curves for each patient were simulated using the Comdyna Dose Generator Analog Computer and the individual actual serum concentrations were monitored . The actually found serum level data were compared to the expected values based on the dosage regimen equations and to the steady state equations . Additionally, the expected peak maxima were calculated . The proposed method resulted in effective and safe kanamycin serum levels. Med J Aust, 1977 Jan 29, 1(5), 133 - 6 Antibiotic sensitivity of gonococci in South Australia, 1974 to 1975; Finger A et al.; Routine testing of gonococci isolated from patients attending the Venereal Diseases Control Centre in Adelaide during the year July, 1974 to June, 1975, with a plate dilution method, showed that 93-8% of the 947 infecting strains were relatively sensitive to penicillin at a minimum inhibitory concentration (MIC) of 0-12 units/ml or less, and that 90% of the 648 strains tested were relatively sensitive to tetracycline at an MIC of 1-0 mug/ml or less . A small proportion only of isolates were relatively insensitive to penicillin and/or tetracycline . The routine treatment schedules which were used at the Centre proved adequate for infections over the whole range of sensitivities encountered . A significant proportion of the less sensitive strains were isolated from people infected in South-East Asia, most of whom had been inadequately treated there. Am J Trop Med Hyg, 1977 Jan, 26(1), 127 - 36 Acedapsone treatment of leprosy patients: response versus drug disposition; Peters JH et al.; In 22 lepromatous Filipino patients receiving their first injection of 225 mg acedapsone (DADDS), dapsone (DDS), and monoacetyl DDS (MADDS) were present in plasma in approximately equal quantities . Peak levels of parent drug, DDS, and MADDS occurred between 22 and 35 days . The half-times of disappearance (T1/2) from plasma were 43 days for DDS and MADDS and 46 days for DADDS . Acetylator phenotyping with sulfamethazine (SMZ) and DDS showed that 17 patients were rapid and 5 patients were slow acetylators . Correlations between acetylation of SMZ and DDS after DDS and of acetylation of DDS after DDS and DADDS were highly significant . However, acetylation of DDS after DADDS did not differentiate the patients into acetylator phenotypes . The T1/2 of DDS after DDS in the patients was directly related to the minimum levels of DDS at 77 days after DADDS treatment . These minimum levels were 8-fold higher than the minimum inhibitory concentration (MIC) of DDS for Mycobacterium leprae in mice and rats, but not all patients responded satisfactorily . No relationship could be demonstrated between the bacteriologic response and any of the pharmacologic parameters examined in these Filipino patients . In a companion study, minimum levels of DADDS, MADDS, and DDS were determined in 447 leprosy patients of all disease types from the Karimui District of Papua New Guinea who had been receiving 225 mg DADDS every 70 to 80 days for the past 5 years . All patients exhibited DDS levels above the MIC of DDS for M . leprae, no significant differences in plasma sulfone levels were found among disease types, no relationship between rate of healing in paucibacillary patients and sulfone levels were found, and type of response in multibacillary patients and sulfone levels were unrelated . No substantial accumulation of the sulfones in the Karimui patients receiving continuous therapy with DADDS for 5 years was indicated from a comparison with the levels in the Filipino patients following a single injection of DADDS. Chemotherapy, 1977, 23 Suppl 1, 365 - 77 Treatment of typhoid fever with fosfomycin alone and associated to chloramphenicol or ampicillin; Figueroa J et al.; Treatment with fosfomycin alone and associated to subtherapeutic doses of chloramphenicol or of ampicillin, has been tried on 50 patients with typhoid fever and on four carriers of S . typhi in the Hospital del Rey . 15 patients were treated with fosfomycin alone, 22 with fosfomycin plus chloramphenicol and 13 with fosfomycin plus ampicillin . The treatment lasted 15-20 days . The results have been evaluated clinically and bacteriologically, haemo- and coprocultures being carried out . The sensitivity of the isolated germs has been studied, including MIC and the synergism in vitro between fosfomycin-chloramphenicol and fosfomycin-ampicillin . Fosfomycin, chloramphenicol and ampicillin determinations have been carried out on the blood . The cures obtained were 67, 82 and 92% respectively with fosfomycin, fosfomycin-chloramphenicol and fosfomycin-ampicillin . We believe that this antibiotic can be useful in the treatment of typhoid fever, associating it to chloramphenicol or ampicillin, due to the synergism existing between them and given the results we have obtained. Arzneimittelforschung, 1977, 27(10), 2023 - 7 {Determination of gentamicin in the serum of patients with normal renal function with the purpose of avoiding subtherapeutic antibiotic levels (author's transl)}; Bickenbach R et al.; In 24 patients with normal renal function the serum concentration of gentamicin was checked during a period of 3--5 days . The biological test is simple and rapid to perform . The patients were given doses of 80--240 mg gentamicin per day . Even at doses of 240 mg/day no accumulation of the drug occurred . Intramuscular application of an 80 mg maximum dose of gentamicin did not result in any toxic serum concentrations . The measurement of peak concentrations--1 h after application--is therefore jus aimed at correcting too low dosages . The median values of the serum peak concentrations are 4--6 microgram/ml in the case of single dose application of 80 mg and 3 microgram/ml in the case of single dose application of 40 mg . Consequently serum concentrations effective against moderately susceptible bacteria (MIC = 1--4 microgram/ml) do not act for a sufficiently long time, since the half-life for elimination is 2 h . Daily dosages of up to 240 mg (3X80 mg) gentamicin are only effective in infections caused by very susceptible bacteria with a MIC up to 1 microgram/ml. Pol J Pharmacol Pharm, 1977 Jan-Feb, 29(1), 69 - 73 Derivatives of 4(7)-methyl- and 5,6-dimethyl-benzimidazolyl-2-mercaptoacetic acids; Czarnocka-Janowicz A et al.; Esters, hydrazides and hydrazones of the in title mentioned acids were prepared and screened for tuberculostatic activity . The strongest activity (MIC at 15-6 mug/cm3) was shown by hydrazide 4 and its hydrazone 4a. Pol J Pharmacol Pharm, 1977 Jan-Feb, 29(1), 61 - 8 Studies on pyrazine derivatives . Part VII . Synthesis and tuberculostatic activity of some pyrazine amidines and amidoximes; Foks H et al.; In the reaction of 2-cyano-6-alkylaminopyrazines with sec . amines in the presence of anhyd . AlCl3 amidines 1-13 were obtained . From pyrazine-2-imidoesters, 2-cyano-pyrazines and pyrazine-2-carbothioamides and hydroxylamine, amidoximes 14-49 were easily prepared . These new compounds were, however, of little tuberculostatic activity (MIC between 31.5-2000 mug/cm3). Chemotherapy, 1977, 23 Suppl 1, 310 - 4 Enteropathogenic E . coli gastroenterocolitis in neonates treated with fosfomycin; Taylor CG et al.; The effect of calcium salt of fosfomycin in the treatment of 43 neonates suffering from acute gastroenterocolitis produced by enteropathogenic E . coli is evaluated . The minimal inhibitory concentration of these E . coli was, generally, lower than 128 mug/ml . Dosages of 150-200 mg/kg body weight/day were administered orally every 8 h . This treatment lasted for 4 days only . Clinical evolution was favorable in 38 (88%) babies and bacteriological evolution in 30 (70%) . In eight cases a different flora to the initial was selected during the treatment with fosfomycin . None of the cases treated showed any toxic alteration attributed to the antibiotic. Scand J Infect Dis, 1977, 9(3), 221 - 6 Studies on the clinical efficacy, serum levels and side effects of clindamycin phosphate administered intravenously; Hugo H et al.; Clindamycin phosphate was administered intravenously to 41 patients with different types of infections including osteomyelitis, septicaemia and soft tissue infections . All bacterial strains tested showed low MIC values for clindamycin . Maximum serum concentrations after 600 mg intravenously were 6.0--29.0 microgram/ml, after 300 mg intravenously 2.6--26.0 microgram/ml . The therapeutic effect of the drug was considered good in 26 of 31 patients with proven or probable bacterial aetiology . Side effects were noted in 16 of the 41 patients . However, in only 5 of these the treatment had to be terminated, all due to pruritic rashes . In the 7 cases with diarrhoea as side effect, the symptoms were mild and of short duration. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol, 1977, 88(3), 261 - 72 {Partial synchronization of tumor cells in vivo with hydroxyurea (author's transl)}; Hartenstein R et al.; For the partial synchronization of tumor cells, Yoshida ascitic sarcoma bearing rats were treated with Hydroxyurea using two methods, one in the form of a single intraperitoneal injection (0.5 mg/g body weight) and the other by continuous intraascitic infusion over a period of 12h (1.428 mg/g body weight total dose) . The synchronization obtained by continuous infusion of Hydroxyurea is superior to that by a one time injection with respect to cell accumulation in one phase of the cell cycle and in the duration of synchronous proliferation . The degree of cell loss caused by infusion depends on the concentration of Hydroxyurea . Concentrations of slightly more than the minimal inhibitory concentration of DNA synthesis cause the least damage to the tumor cells. Chemotherapy, 1977, 23 Suppl 1, 429 - 40 Fosfomycin in pneumococcal meningitis; Sicilia T et al.; A study has been made of 12 patients with pneumococcal meningitis with ages ranging from 12 months to 59 years . In all cases pneumococcus was isolated in the cerebrospinal fluid (CSF) . Seventeen pneumococci were studied for their sensitivity to fosfomycin, ampicillin and gentamicin, including their MIC . All were sensitive to fosfomycin and ampicillin and 7 to gentamicin . On the other hand there has also been made a study of the interaction between fosfomycin plus ampicillin and fosfomycin plus gentamicin . The concentration of antibiotics in plasma and CSF had been determined . The association of fosfomycin to penicillin or ampicillin was also studied in some cases, depending on whether the patient was younger or older than 2 years, and in other cases, the association of fosfomycin with gentamicin . The concentrations of antibiotics in the CSF varied according to the stage of evolution of the meningitis . As regards clinical results, 10 cures and 2 failures have been obtained . The pneumococcus was eradicated from the CSF in all cases, including the two failures, in the control carried out 2-3 days after beginning of treatment, the rest of the analytical data of the CSF became normal within 5 and 17 days treatment. Chest, 1976 Dec, 70(6), 755 - 9 R34000, a dioxolane imidazole in the therapy for experimental coccidioidomycosis . Comparison with miconazole and econazole; Levine HB; Comparisons were made on the therapeutic influence of three imidazole drugs in experimental lethal coccidioidomycosis of mice . When administered by the intramuscular route, miconazole and a closely related structural analogue, econazole, were effective in preventing death, restricting fungal replication in the lungs, and minimizing the extent of extrapulmonary dissemination . Neither drug was as effective when administered by the oral route as by the intramuscular route . This contrasted sharply with results obtained using R34000, a dioxolane imidazole . It was very highly effective when administered by the oral route and less so by intramuscular injection . All orally treated mice survived a challenge lethal to more than 80 percent of control animals . Plasma or serum concentrations of orally administered R34000 in mice and in man exceeded the minimum inhibitory concentration for a virulent strain of Coccidioides immitis. J Clin Pathol, 1976 Dec, 29(12), 1097 - 100 Sensitivity of Brucella spp to tetracycline and its analogues; Farrell ID et al.; The sensitivity to eight tetracyclines of 100 strains of brucellae, comprising strains of Brucella abortus, Br . melitensis, and Br . suis, was determined . Demethylchlortetracycline was the most effecitve against all the groups of brucellae, whereas oxytetracycline and chlortetracycline were the least effective . The mean MIC value for demethylchlortetracycline, doxycycline, lymecycline, and tetracycline was less than or equal to 1 mug/ml . Strains of Br . abortus biotype 2 and Br . suis were the most sensitive strains examined. Am J Trop Med Hyg, 1976 Nov, 25(6), 854 - 9 Dapsone chemotherapy of Mycobacterium leprae infection of the neonatally thymectomized Lewis rat; Fieldsteel AH et al.; In order to learn whether the neonatally thymectomized Lewis rat (NTLR) infected with Mycobacterium leprae could serve as a model for chemotherapeutic studies in a situation resembling that found in human lepromatous leprosy, NTLR inoculated with M . leprae either locally or intravenously 9 to 16 months earlier were treated for from 1.5 to 8.5 months with dapsone (4,4'-diaminodiphenylsulfone, DDS) incorporated in the rat chow in the concentration providing the minimal inhibitory concentration of the drug for M . leprae and in the 100-fold larger concentration . NTLR were killed at intervals; the M . leprae were counted and passed to mice . Treatment with the smaller dosage of dapsone neither killed M . leprae nor reduced the number of organisms in the bacterial populations, whereas treatment with the larger dosage both killed M . leprae and reduced their numbers . The rate at which the organisms were killed (i.e., rendered noninfective for mice) was much the same as that in patients treated with dapsone in comparable dosage . The dead organisms were removed from the rat tissues at a faster rate than encountered in patients . The NTLR may indeed be suitable for chemotherapeutic studies relevant to man . In addition, the more rapid disappearance of dead M . leprae from the rat tissues may facilitate the study of treatment regimens designed to eradicate persisting viable organisms. Lipids, 1976 Oct, 11(10), 755 - 62 Structure-function activity of azasterols and nitrogen-containing steroids; Kabara JJ et al.; Thirty-nine nitrogen-containing steroids were tested against two gram-negative, five gram-positive, and two yeast organisms . Many of these steroids have been previously reported to inhibit various metabolic processes involving sterol metabolism . While low minimal inhibitory concentration (MIC) values were recorded for sterol producing yeast, growth of bacteria which contain no sterols was also inhibited . Structure-function studies provided no relationship between biological activity and hypocholesteremic effects of these azasteroids . A hypothesis put forward is that amino and azasteroids are effectors of membrane which, in the case of mitochondria, lead to changes in adenosine triphosphate levels and/or dehydrogenase activity . Their effects on sterol metabolism, therefore, may be of secondary consideration. J Infect Dis, 1976 Oct, 134(4), 400 - 4 Differential sensitivity of herpes simplex virus types 1 and 2 to human interferon: antiviral effects of interferon plus 9-beta-D-arabinofuranosyladenine; Lerner AM et al.; With use of a standard assay for antiviral compounds, in which the compound to be tested is added after absorption of virus, the minimal inhibitory concentration (MIC) of human interferon for several strain of herpes simplex virus type 2 (HSV-2) is five to 10 times greater than it is for two strains of herpes simplex virus type 1 (HSV-1) . This differential susceptibility of HSV types to interferon is found whether tests are done with a liquid overlay and microtiter plates or with agarose overlays and appears to be a distinguishing biological marker . When the MIC of interferon is tested by microtiter or agarose methods and interferon is allowed to incubate for 24 hr before virus is added, values for HSV-1 and HSV-2 are similar and much smaller in magnitude . These results support earlier data indicating that adenine arabinoside and interferon are synergistic against herpes simplex virus type 1 in vitro and indicate that these agents are additive but not synergistic against herpes simplex virus type 2. Pediatrics, 1976 Sep, 58(3), 382 - 7 Evaluation of a rapid beta-lactamase test for detecting ampicillin-resistant strains of Hemophilus influenzae type b; Scheifele DW et al.; Chloramphenicol is presently the drug of choice in the initial treatment of serious infections due to Hemophilus influenzae type b . Rapid detection of ampicillin resistance in clinical isolates would facilitate early discontinuation of chloramphenicol therapy in patients infected with ampicillin-sensitive bacteria . A total of 160 strains of H . influenzae type b were tested with a one-hour acidimetric microassay for beta-lactamase activity . All ampicillin-resistant strains rapidly hydrolysed the beta-lactam ring of penicillin . When isolates were encoded and tested without knowledge of their MICs, the 40 ampicillin-resistant strains (MIC greater than or equal to 2 mug/ml) were readily distinguished from 120 sensitive strains . Rapid beta-lactamase assay is therefore a reliable detector of ampicillin resistance in H . influenzae type b. J Am Vener Dis Assoc, 1976 Sep, 3(1), 32 - 4 Changing penicillin resistance of the gonococcus in Thailand; Spence MR et al.; Minimum inhibitory concentrations (MIC) of penicillin in units per milliliter were determined for 2.241 gonococcal isolates submitted to the SEATO Medical Research Laboratory between January 1, 1972, and December 31, 1974 . Isolates were separated into 3 groups, determined by the calender year in which they were submitted . The mean penicillin MIC+/-2 standard errors was calculated for each of the 3 groups . These values were 0.58+/-0.02 units/ml in 1972, 0.72+/-0.04 units/ml in 1973, and 1.05+/-0.04 units/ml in 1974 . These means were found to be significantly different (p less than 0.0001). Jpn J Antibiot, 1976 Aug, 29(8), 725 - 30 {Studies on the disc method for the determination of bacterial sensitivity to ribostamycin (author's transl)}; Kanazawa Y et al.; The MICs of ribostamycin (RSM) were determined by the two-fold serial agar-dilution method of 109 bacterial strains of 20 species . The diameters of inhibition zones of these bacterial strains by the 50 mug RSM disc were also measured . The relation between the MIC and the diameter of the inhibition zone was found to be expressed as a primary regression line in all cases of the conventional method (cultured for about 16 hours), delayed assay method (cultured for about 24 hours) and rapid methods (5 approximately 6 hours and 3 approximately 4 hours culture methods) . Thus, it was confirmed that the single-disc method can be employed for the susceptibility test of RSM . Subsequently, variations of MICs obtained by the disc-diffusion method were compared with those obtained by the serial agar-dilution method. J Am Geriatr Soc, 1976 Aug, 24(8), 344 - 54 Pharmacokinetic approach to drug dosing in the aged; Ritschel WA; Data in the literature show that there is a constant ratio of total body fluid to lean cell mass with increasing age (1.15 for males and 1.31 for females) . Since the drug receptors usually are found in the tissues, and since cell mass and total body fluid apparently decrease at a constant rate, it would seem that the volume of distribution of drugs decreases proportionally with increasing age . Kidney function, as measured by the glomerular filtration rate and transport maximum, apparently decreases with increasing age according to zero-order kinetics . Based on these data, correction factors were established for the change in volume of distribution and renal functions with increasing age . Equations were derived for calculating the loading dose and maintenance dosage of drugs in multiple-dose therapy in females and males . Equations are presented for drugs following the minimal inhibitory concentration (MIC) pattern and the log dose-response pattern, respectively . The MIC pattern is recommended in the use of bacteriostatic drugs, for which it is essential to maintain recommended in the use of bacteriostatic drugs, for which it is essential to maintain during the entire course of therapy a minimum inhibitory concentration . The log dose-response pattern is recommended for bactericidal and antiarrhythmia drugs, for which it is essential to obtain an average therapeutic steady-state concentration . Based on this pharmacokinetic approach, it would seem that elderly patients, during multiple-dose therapy, are exposed to dose sizes that are too large if no correction is made. MMW Munch Med Wochenschr, 1976 Jul 30, 118(31), 987 - 90 {Polyacrylic bone cement with added erythromycin and colistin . In vitro studies on bacteriologic activity and diffusion properties}; Rosenthal AL et al.; Erythromycin and colistin are not antagonists and have the property of inhibiting the growth of a large number of aerobic and anaerobic organisms . When they were worked into Chirurgischen Knochenzement Simplex P Radiopaque, the growth of 98% of all anaerobic and aerobic test organisms was inhibited . Separately conducted investigations have shown that each antibiotic can diffuse out of polymerized cement and that the concentration of each antibiotic is far above the minimal inhibitory concentration (MIC) of 96% of the organisms . Consequently, in our opinion it would be of benefit to test the Chirurgische Knochenzement Simplex P Radiopaque with erythromycin and colistin clinically. J Dent Res, 1976 Jul-Aug, 55(4), 574 - 9 Susceptibility of some plaque microorganisms to chemotherapeutic agents; Newbrun E et al.; Investigators have used chemotherapeutic agents topically for plaque control without knowing the drug concentration necessary to inhibit the growth of odontopathic microorganisms . S mutans, S sanguis, A viscosus and A naeslundii are important components of the plaque flora . The minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) of niddamycin, vancomycin, bacitracin, and kanamycin were determined for each organism in liquid culture . These antibiotics were selected because of their low absorption from the gastrointestinal tract . Niddamycin, vancomycin, and bacitracin had the lowest MIC, from 0.2 to 10 units/ml . Kanamycin was inhibitory only at much higher concentrations (130 to 500 units/ml) . The corresponding MBC was generally higher than the MIC . A viscosus was the most resistant organism tested . These data are important in designing controlled release devices for delivering a suitable antibiotic on a continuous basis intraorally. Ann Microbiol (Paris), 1976 Jul, 127(1), 57 - 68 {The resistance of "Pseudomonas" to antibiotics and heavy metal: minimal inhibitory concentrations and genetic transfers (author's transl)}; Joly B et al.; The antibiotic sensitivity of 43 strains of Pseudomonas and the minimal inhibitory concentration of mercurial derivatives (5 mineral salts and 4 organics compounds) and of silver nitrate to these microorganisms have been studied . Twelve of these strains were P . aeruginosa of hospital origin, and 31 were Pseudomonas from surface water . Resistance against these inhibitory substances let us to established some connections between the different strains . Some strains were selected to transfer resistance markers by conjugation. J Invest Dermatol, 1976 Jun, 66(6), 351 - 4 Detection of human contact sensitivity to dinitrochlorobenzene by the migration inhibiton test; Nishioka K; The migration inhibitory factor (MIF) production of peripheral lymphocytes following exposure to dinitrophenylated microsomes derived from both human (DNP-hy-Mic) and guinea pig (DNP-gp-Mic) epidermis was quantitated to detect human contact sensitivity to dinitrochlorobenzene (DNCB) . The lymphocytes from nonsensitized subjects did not generate MIF following exposure to either antigen . With DNP-gp-Mic as the antigen, MIF production was noted in only 1 out of 6 DNCB-sensitized subjects and was not significant statistically . With DNP-hu-Mic as the antigen, highly significant MIF production was observed in all 12 sensitized subjects ( p less than 0.0005) . In order to confirm MIf production by sensitized lymphocytes following stimulation by DNP-hu-Mic, the subjects were actively sensitized with DNCB and MIF production was assessed before and after sensitization . Remarkable MIf production was noted in the lymphocyte cultures after sensitization, although no significant MIF production was observed before sensitization . MIF production of the sensitized lymphocytes cultured in the presense of DNP-hu-Mic generally correlated well with the results of patch testing, but not with the intensity of the skin test. Antibiotiki, 1976 May, 21(5), 426 - 9 {Comparative study of the effect of antibiotics-aminoglycosides on pseudotuberculosis bacterium in vitro and in vivo}; Ryzhko IV et al.; It was found that 229 out of 230 strains of pseudotuberculosis microbes tested were sensitive to aminoglycosides, such as streptomycin, monomycin, neomycin, kanamycin and gentamicin . The MIC did not exceed 50 gamma/ml . One strain of J . pseudotuberculosis was multiresistant to streptomycin, tetracycline, levomycetin and penicillin . The above aminoglycosides (streptomycin, monomycin, kanamycin and gentamicin) were active in the treatment of albino mice with experimental pseudotuberculosis. J Hyg (Lond), 1976 Apr, 76(2), 191 - 203 Antibiotics and the Aberdeen typhoid outbreak in 1964; Brodie J; This paper gives an abbreviated account of part of a research programme which followed the Aberdeen typhoid outbreak in 1964 . Chloramphenicol, the main antibiotic used in treatment, was shown to have a minimum inhibitory concentration (MIC) of between 5 and 2-5 mug./ml . for the S . typhi phage type 34 of the outbreak . The MIC for methacycline was between 5 and 2-5 and 2 mug./ml . Whereas the deep and shallow broth techniques used gave similar results with these antibiotics, the MIC for ampicillin, and also cephaloridine, was less in the deep than in the shallow broths . Serum assays in patients given ampicillin or cephaloridine yielded abnormally high concentrations of both antiboitics when S . typhi phage type 34 was the test organism whereas, with other test organisms, the concentrations were within expectation . These abnormally high values fell within expected values when the sera under investigation had first been heated to 56 degrees C . for 30 min . before assay against the S . typhi of the outbreak . The findings with ampicillin suggested that dosages given were satisfactory . With cephaloridine the concentrations found in patients' sera seemed to show that twice daily doses of 0-5 g . fell short of adequacy. Chemotherapy, 1976, 22(3-4), 242 - 52 In vitro and in vivo studies of the action of rifampicin, clofazimine and B1912 on Mycobacterium marinum; Banerjee DK et al.; Rifampicin (RMP) and two riminophenazine compounds (B663 and B1912) suppressed the growth of Mycobacterium marinum in vitro and in a mouse footpad infection . At appropriate concentrations and dietary dosage, all three drugs showed bactericidal activity in vitro and in vivo . On the basis of minimum inhibitory concentration, RMP was considerably more active than the other two substances in vitro . However, the rate of bactericidal effect was similar for all three drugs . In vivo, the minimum bactericidal dietary dosages of RMP, B663 and B1912 were 0.03, 0.03 and less than or equal to 0.01%, respectively . Results suggest that these drugs may be of value for the treatment of clinical M . marinum infections. J Int Med Res, 1976, 4(5), 296 - 304 Polyacrylic bone cement containing erythromycin and colistin . I . In vitro bacteriological activity and diffusion properties of erythromycin, colistin and erythromycin/colistin comibination; Rosenthal AL et al.; Erythromycin and colistin demonstrate a non-antagonistic ability to inhibit the growth of a wide variety of aerobic and anaerobic bacterial isolates . When incorporated in Surgical Simplex P Radiopaque Bone Cement, fabricated cement pellets were effective in inhibiting 98% of all anaerobic and aerobic test isolates . Separate experiments indicate that each antibiotic can diffuse from polymerized cement, and that the concentration of each antibiotic is consistently above the minimum inhibitory concentration of 96% of the isolates . We conclude that erythromycin/colistin Surgical Simplex P radiopaque Bone Cement is a worthy candidate for clinical investigation. Scand J Infect Dis Suppl, 1976, (9), 78 - 81 Aspects of the treatment of maxillary sinusitis; Carenfelt C et al.; The elimination of bacteria from sinus secretion during antibiotic treatment and the biological environment in the sinus as regards pO2 and pCO2 of sinus secretions were studied . Elimination of bacteria was achieved only, but not invariably, when the antibiotic concentration in the secretion greatly exceeded the MIC values of the bacteria isolated . Bacteriostatic and bactericidal antibiotics were equally effective . In purulent secretions as opposed to nonpurulent secretions the pO2 was always zero or close to zero, and the pCO2 was always higher than, and sometimes more than twice as high as the pCO2 of venous blood . In view of these observations, antibiotic therapy resulting in a high antibiotic concentration in the secretion is advocated in the treatment of purulent maxillary sinusitis . Furthermore, drainage and aeration of the sinus cavity is to be regarded as an important complement to the antibiotic therapy. Arch Immunol Ther Exp (Warsz), 1976, 24(1), 121 - 5 Action of helenin on microorganisms; Kowalewski Z et al.; The action of helenin on 10 genera of bacteria and yeasts and on 8 genera of dermatophytes was studied . The minimal inhibitory concentration for gram-positive bacteria ranged from 10 to 400 mug/ml, for gram-negative bacteria from 100 to 800 mug/ml, for yeasts from 200 to 750 mug/ml, and for dermatophytes from 50 to 500 mug/ml . Strains naturally resistant to helenin are very rare. Scand J Infect Dis Suppl, 1976, (9), 100 - 5 Concentration of doxycycline in bowel tissue and postoperative infections; Hojer H et al.; An investigation on the relation between the effect of doxycycline as prophylactic antibiotic in colonic surgery and levels of doxycycline in serum and bowel tissue with reference to MIC-values of bacterial strains isolated at surgery or after postoperative septic complications is presented . 200 mg doxycycline orally 4-6 hours preoperatively resulted in a serum concentration of 4.0 +/- 0.3 mug/ml at the onset of operation . Tissue samples removed at surgery were assayed for doxycycline . High levels were observed in bowel tissue, ileum 7.5 +/- 1.2 mug/ml and colon 3.9 +/- 0.3 mug/ml . The effects of dosage, time of administration and bowel pathology on tissue levels are discussed . Aerobic and anaerobic bacterial strains were tested for in vitro susceptibility to doxycycline using a standardized disc-diffusion method according to Eriksson and Sherris . 75% of the strains belonged to sensitivity groups 1 and 2 (sensitive-fairly sensitive) . That is, MIC-values in 75% of the strains were below the average serum and intestinal tissue concentration during the operation . The implications of these results are that the dosage and time of administration of the drug must be adjusted so that serum and tissue levels are adequate during surgery. Chemotherapy, 1976, 22(5), 313 - 8 Relationships between in vitro susceptibility and efficacy in experimental mouse infection-protection assay of cefazolin and cephalothin using Escherichia coli strains; Uri JV et al.; The disc sensitivity and minimal inhibitory concentrations (MIC) of cefazolin and cephalothin were compared against a series of Escherichia coli isolates . These data were correlated with the mouse protective doses of the 2 cephalosporins in animals infected with E . coli strains selected according to their various degrees of in vitro sensitivity to the 2 cephalosporins . The overwhelming majority of E . coli strains showed a significantly higher degree of susceptibility and lower MIC values for cefazolin than for cephalothin . There has been found a good correlation between the inhibition zones and especially the MIC values and the ED50 results for both cephalosporins . Using E . coli clinical isolates, cefazolin was found to be superior to cephalothin not only in vitro experiments but also more potent in protecting the experimentally infected mice. Int J Clin Pharmacol Biopharm, 1975 Dec, 12(4), 395 - 402 The correlation between the clinical effectiveness and ratio of blood concentration to minimum inhibitory concentration of sulfamethoxazole against Escherichia coli isolates . The determination of a parameter in a dosage equation by the pharmacokinetics; Otaya H et al.; The correlation between the clinical effectiveness and ratio of blood concentration to minimum inhibitory concentration of sulfamethoxazole against Escherichia coli isolated from clinical specimens were studied . This value is one of important parameters in a dosage equation by the pharmacokinetics, it showing sigma in an equation, were determined by clinical trial for acute simple cystitis of women . The sigma values were justified as 4 or more. Jpn J Antibiot, 1975 Dec, 28(6), 745 - 52 {Studies on the disc method for the determination of bacterial sensitivity to sulfobenzylpenicillin (author's transl)}; Kanazawa Y et al.; The MIC''s of sulfobenzylpenicillin (SB-PC) were determined by the two-fold serial agar-dilution method for 108 bacterial strains of 21 species . The diameters of inhibition zones of these bacterial strains by the 30 mug and 200 mug SB-PC discs were also measured . The relation between the MIC and the diameter of the inhibition zone was found to be expressed as a primary regression line in all cases of the conventional method (cultured for about 16 hours), delayed assay method (cultured for about 24 hours) and rapid methods (5 to approximately 6 hours and 3 to approximately 4 hours culture m ethods) . Thus, it was confirmed that the single-disc method can be employed for the susceptibility test of SB-PC . Subsequently, variations of MICs obtained by the disc-diffusion method were compared with those obtained by the serial agar-dilution method. Boll Ist Sieroter Milan, 1975 Nov 20, 54(5), 378 - 81 {Anti-mycoplasmatic activity of 2 antracyclinic antibiotics}; Buogo A et al.; The antimycoplasma activity (bacteriostatic and bactericidal) of daunomycin and adriamycin has been tested on 14 strains in liquid and solid medium . The minimal inhibitory concentration (MIC) values of daunomycin and tetracycline have resulted of the same greatness, while those regarding adriamycin are lightly greater. Med J Aust, 1975 Nov 8, 2(19), 740 - 2 Antibiotic sensitivity pattern of pneumococci relatively insensitive to penicillin and cephalosporin antibiotics; Hansman D; Penicillin-insensitive pneumococci, of 10 serotypes, which had been isolated in Australia and New Guinea from healthy carriers and patients with pneumococcal infections, were shown to be relatively resistant to penicillin G, penicillin V, methicillin, cloxacillin, cephaloridine and cephalothin, compared with pneumococci fully sensitive to penicillin G . Most penicillin-insensitive pneumococci either were fully sensitive to ampicillin or showed a slight decrease in sensitivity . The size of inoculum, measured in viable units, had little effect on the minimal inhibitory concentration of penicillin G; this applied to both penicillin-insensitive and penicillin-sensitive pneumococci . In bacterial tests, the minimal bactericidal concentration of penicillin G either equalled or exceeded the minimal inhibitory concentration. Schweiz Med Wochenschr, 1975 Nov 1, 105(44), 1427 - 32 {Proceedings: Microbiology of endocarditis}; Waldvogel FA; The classical paper published by Schottmuller in 1903 has shown beyond doubt that blood cultures are a crucial diagnostic procedure for the diagnosis of endocarditis . Positive blood cultures also make it possible to distinguish between bacteremia and endocarditis: in the latter condition the number of organisms per ml of blood is relatively constant and all blood cultures are usually positive . Gram positive cocci are still the commonest organisms found in classical endocarditis . Gram negative organisms, yeasts and fungi are cultured with increasing frequency in cases of endocarditis secondary to valve replacement . Sensitivity testing by the disc diffusion method determines the minimal inhibitory concentration of the antibiotic towards the isolated organism . However, minimal bactericidal concentrations are of much greater prognostic value in endocarditis and should be performed routinely on the isolated organism. J Gen Microbiol, 1975 Nov, 91(1), 110 - 8 The activity of polymyxins against dense populations of Escherichia coli; Greenwood D; The activities of polymyxin B sulphate, colistin (polymyxin E) sulphate and their sulphomethyl derivatives were compared by continuous turbidimetric monitoring of dense cultures of an Escherichia coli strain exposed to these agents . Judged by the concentration of antibiotic which caused a rapid fall in opacity of the culture, polymyxin B sulphate and colistin sulphate had similar activities, but the sulphomethyl compounds differed considerably: sulphomyxin sodium induced lysis of the culture at a concentration four times that of the parent compound, whereas colistin sulphomethate sodium induced a delayed fall in opacity consistent with recruitment of activity as the inactive sulphomethyl derivative was broken down to the parent compound . Durign overnight incubation, regrowth of cultures which had initially succumbed to polymyxin action occurred, apparently due to the selection of phenotypically resistant variants from within the population . In this way cultures could easily be adapted to growth in concentrations of antibiotic well above the conventionally-determined minimum inhibitory concentration . The comparative ease of adaptation was in the order: colistin sulphomethate greater than sulphomyxin greater than colistin sulphate greater than polymyxin B sulphate. Int J Oral Surg, 1975 Oct, 4(5), 198 - 204 Penicillin treatment in oral surgery in patients with coagulation disorders; Lundberg C et al.; There are clinical observations indicating that the frequency of postoperative bleeding after oral surgery in patients with coagulation disorders is reduced by prophylactic antibiotic treatment . To assess this effect, the concentrations of phenoxymethylpenicillin in plasma and saliva were determined during treatment and compared with the MIC values for penicillin of the oral bacteria of four patients with coagulation disorders . The concentration of penicillin in plasma of the patients considerably exceeded the MIC values of all isolated bacteria . In mixed saliva and saliva of the parotid and submandibular glands no penicillin activity could be detected . The bacteria isolated from the oral cavity of the patients did not in vitro exhibit either fibrinolytic or plasminogen activator activity . Thus, the oral bacteria of patients with coagulopathies probably do not cause an increased bleeding tendency by their intra- or extracellular enzymes. Arzneimittelforschung, 1975 Sep, 25(9), 1442 - 7 Dose size and dosing interval determination; Ritschel WA; Knowing the necessary minimum inhibitory or minimum effective concentration of a drug dose size and/or dosing interval for multiple dose therapy can be calculated under the assumption that the blood level-time curve of a drug can be described by an open one-compartment or an open two-compartment model, that the drug does not show dose dependent pharmacokinetics for the therapeutic dose range and that the distribution coefficient is applicable for a wide body weight range and age group, excluding severe edemas and obesity . The dose size and dosing interval equations are derived from the minimum blood-level concentration c'min equation in multiple dosing . Substituting c'min by MIC or MEC, cop by D - f/Vd and Vd by delta' - BW either the required dose size or dosing interval can be calculated . In the case of renal failure adjustment can be made by inclusion of a correction factor into the equations using either the observed creatinine clearance or the serum creatinine value. Southeast Asian J Trop Med Public Health, 1975 Sep, 6(3), 322 - 7 Serial dilution antibiotic susceptibility testing evaluation of a micromethod for use in a diagnostic laboratory; Thong ML et al.; Simultaneous MIC determinations were performed by the conventional tube dilution method and a microdilution technique . Forty-five clinical isolates and 11 antibiotics were used . Results of the two tests revealed 89.2% aggrement of +/- one dilution . The microdilution method was found to be reliable, reproducible and economical in time, labour and materials . The use of pH indicator in the microtechnique is recommended for certain organisms. Proc Natl Acad Sci U S A, 1975 Sep, 72(9), 3623 - 7 Translocation of a plasmid DNA sequence which mediates ampicillin resistance: molecular nature and specificity of insertion; Heffron F et al.; A series of recombinant plasmids was generated in Escherichia coli in which the TEM beta-lactamase translocon (TnA) was inserted into the small plasmid RSF1010 . RSF1010 is a 5.5 X 10(6) dalton nonconjugative plasmid which confers resistance to streptomycin and sulfonamide . The recombinant plasmids can be classified into three clearly defined phenotypic groups . Group I is ampicillin-, streptomycin- and sulfonamide-resistant . Group II is ampicillin- and sulfonamide-resistant but has lost streptomycin resistance . Group III is ampicillin-resistant but is sensitive to sulfonamide and shows a simultaneous 30-fold reduction in the minimal inhibitory concentration of streptomycin . It was possible to map the site of insertion of TnA within RSF1010 by electron microscope studies of DNA heteroduplexes formed between RSF1010 and recombinant plasmids . Insertions of TnA occur at, at least, 12 distinct sites in a region corresponding to one-third of the RSF1010 DNA molecule . Those insertions giving rise to particular phenotypes are clustered . Insertions of TnA-like insertion sequences (IS) appear to give rise to strongly polar mutations. Br J Vener Dis, 1975 Aug, 51(4), 265 - 6 Minimum inhibitory concentrations of penicillin and minocycline for 300 isolates of N . gonorrhoeae; Shahidullah M et al.; The minimum inhibitory concentrations of penicillin and minocycline were measured on 300 consecutive isolates of N . gonorrhoeae from patients attending the Nottingham treatment centre . 210 (70 per cent.) of these were fully sensitive to penicillin (MIC less than 0-1 mug./ml) and 89 per cent . were fully sensitive to minocycline (MIC less than 0-5 mug./ml.) . Of the nine strains resistant to penicillin (MIC less than or equal to 0-5 mug./ml.), eight were also of reduced sensitivity to minocycline. Br J Vener Dis, 1975 Aug, 51(4), 246 - 50 Distribution of levels of penicillin resistance among freshly isolated strains of N . gonorrhoeae . Application of a novel sensitivity assay; Shannon R et al.; A novel diffusion zone method of quantitative assay of the antibiotic sensitivity of bacterial strains was tested on freshly isolated gonococci . Smoothly variable estimates of the minimum inhibitory concentration of penicillin for these strains was obtained with sufficient accuracy and precision (coefficient of variation c . 10 per cent.) by means of a simple graphical analysis and without replication . Such estimates were free from the chief sources of error associated with the commonly applied 'incorporation' and 'diffusion' methods . The method revealed that 816 isolates of gonococci obtained in the Bristol area during a 6-month period fell into a large 'sensitive' group (MIC c . 0.02 unit per ml.) and three smaller more resistant groups, and that this pattern occurred in three widely spaced centres within the area . It is suggested that the method is capable of revealing details of distribution that may be masked by the usual techniques and that it is of wide applicability. J Infect Dis, 1975 Jul, 132(1), 82 - 6 Synergism of amphotericin B and 5-fluorocytosine for candida species; Montgomerie JZ et al.; The in vitro activity of amphotericin B and 5-fluorocytosine against 40 isolates of different species of Candida was studied . Synergism was seen in 35 of 40 organisms studied (88%) with achievable serum concentrations of the antibiotics . Synergism was striking in many strains that were resistant to 5-fluorocytosine . When the minimal inhibitory concentration of 5-fluorocytosine was greater than 400 mug/ml, synergism was seen in 18 of 20 isolates of Candida (90%). Ann Microbiol (Paris), 1975 Jul-Aug, 126B(1), 51 - 61 {The role of heavy metals and their derivatives in the selection of antibiotics resistant gram-negative rods (author's transl)}; Joly B et al.; The authors have studied 116 Gram-negative strains, 27 of which were sensitive to antibiotics and 89 showed multiple resistance . The MIC of mercury chloride, mercuric nitrate and of an aqueous solution of mercuresceine were much higher in the case of the sensitive strains . The transfer of resistance to mercury, which has been achieved in 56% of cases, was always accompanied by transfer of resistance to the antibiotics . The MIC of phenylmercury borate, mercurothiolic acid and other heavy metals (such as: cobaltous nitrate, silver nitrate, cadmium nitrate, nickel nitrate, zinc nitrate, copper sulphate and sodium arsenate) are approximatively the same for all strains . The normal concentrations of mercury in nature are lower than the rate of microbial selection . But in areas of accumulation, particularly in biological chains or in hospitals, the mercury compounds could play a part in the selection of antibiotic resistant Gram-negative bacteria. Ann Microbiol (Paris), 1975 Jul-Aug, 126B(1), 41 - 9 Sensitivity and resistance of pathogenic yeasts to 5-fluoropyrimidines . II.--Mechanisms of resistance to 5-fluorocytosine (5-FC) and 5-fluorouracil (5-FU) (author's transl)}; Montplaisir S et al.; Incorporation of labelled 14C-pyrimidines and 5-fluoropyrimidines (5-FC and 5-FU) in four different phenotypes of wild strains of Candida isolated from man showed comparable results to those obtained by the minimal inhibition concentration (MIC) test . Kinetics studies demonstrated significant rates of incorporation after 24 hours of culture in each case . It was also possible to infer the biochemical mechanisms of resistance to 5-FC, namely a defect in UMP pyrophosphorylase, cytosine deaminase and 5-FU permease in the ease of the following phenotypes: 5-FCR 5-FUR, 5-FCR 5-FUS and 5-FCS 5-FUR (R = resistant; S = sensitive) . In this study, the permeation process was approached by a consumption assay which determined the rate of labelled substrates into the medium before and after 24 hours of culture . Thus, it was found that the consumption levels of the phenotype 5-FCS 5-FUS were very high, while those of the phenotype 5-FCR 5-FUR were minimal . The 5-FCS 5-FU5 phenotype had no detectable consumption of 5-FU . With regard to the 5-FC5 5-FUS phenotype, it seems that the non-incorporation of 5-FC into the RNAs after the consumption by the yeasts has a feed back effect on the permeation process. J Pharm Sci, 1975 Jun, 64(6), 1057 - 8 Antitubercular activity of substituted 5-oxo-1-thiocarbamoyl-3-pyrazoline-4-alkanoic acid derivatives; Santilli AA et al.; Several novel pyrazolin-5-ones prepared by the cyclization of variously substituted thiosemicarbazone derivatives of ethyl formylsuccinate, ethyl acetylsuccinate, and ethyl acetylglutarate were tested for antitubercular activity against Mycobacterium tuberculosis, human type, strain H37Rv, by a tube dilution technique . Minimum inhibitory concentrations (MIC) for these derivatives ranged from 0.05 to 100 mug/ml . The most active compound was ethyl 3-methyl-1-methylthiocarbamoyl-5-oxo-3-pyrazoline-4-acetate (MIC=0.05-0.1 mug/ml). J Infect Dis, 1975 Jun, 131(6), 673 - 7 Antiviral activity of an adenosine deaminase inhibitor: decreased replication of herpes simplex virus; Williams BB et al.; A unique seven-membered heterocyclic-ring inhibitor of adenosine deaminase was studied . One preparation of the compound inhibited replication of herpes simplex virus in the absence of adenine arabinoside . In this capacity, the minimal inhibitory concentration of deaminase inhibitor for herpes simplex virus type 1 (HSV-1), with 50 percent reduction of plaque-forming units as the end point, was 37.7 mug/ml . This activity compared favorably with the inhibitory activity of ara-hypoxanthine (34.1 mug/ml) . Another preparation of deaminase inhibitor lacked antiviral activity . On the other hand, the adenosine deaminase inhibitor was active at a concentration of 0.009 mug/ml as a potentiator of the inhibition of HSV-1 by adenine arabinoside . The potentiation of adenine arabinoside by deaminase inhibitor is about 4,000 times more potent than the activity of the direct inhibitory effect on HSV-1 . The nature of the possible contaminant of the preparation in question is unknown . Coformycin, another inhibitor of adenosine deaminase, had no antiviral activity in the absence of adenine arabinoside. Acta Otolaryngol, 1975 May-Jun, 79(5-6), 460 - 5 Penetration of azidocillin into the secretion and tissues in chronic maxillary sinusitis and tonsillitis; Jokinen K et al.; The penetration of azidocillin into the sinus mucosa and secretion as well as into tonsils and adenoids was studied . Altogehter 73 patients were included and they were arranged in four groups according to age, diagnosis and drug dose . The average azidocillin concentration was satisfactory and predictable in all tissues and well over the MIC for most upper respiratory tract pathogens studied . In the maxillary antrum secretion the values were much lower and in many cases under the MIC for hemophilus . This is thought to depend upon the drug's being bound to proteins in the secretions . The clinical results were good in all cases and the contribution of the surgical operation, particularly in providing drainage for the secretion, is obvious. Clin Orthop, 1975 May, (108), 138 - 44 Antibiotics in human hematoma and wound fluid; Nelson CL et al.; Using the total hip replacement patient, we measured the level of antibiotic in the wound at the time of surgery, the wound drainage for 36 to 48 hours after surgery and over a 10 day period in incubated surgical debris obtained at the time of total hip replacement . The antibiotics sodium oxacillin, lincomycin hydrochloride and sodium cephalothin were administered in standard doses at 6 hour intervals . In one group of patients the antibiotic was begun at the time of surgery, in a second group the antibiotic was begun 24 hours after the completion of surgery . Sodium oxacillin, lincomycin hydrochloride and sodium cephalothin produce antibiotic levels in the venous serum consistently above the level obtained in the simultaneous would drainage specimens . Sodium oxacillin and lincomycin hydrochloride used as described in this study are capable of bathing the area of the surgical wound with concentrations of antibiotics above the minimal inhibitory concentrations . This is evidenced by the antibiotic levels above minimal inhibitory concentrations found in the wound drainage . Sodium cephalothin levels in the wound drainage were below measurable levels in 3 of 4 patients . Sodium oxacillin and lincomycin hydrochloride antibiotic levels in the surgical wound debris and simultaneous venous clotted specimens diminished progressively in a similiar manner indicating no additional effects of the surgical wound debris on the antibiotic's biologic effectiveness . Sodium cephalothin dropped below measurable levels in three days . Measurable levels of antibiotics appeared in the wound aspirate well above the minimal inhibitory concentration in patients receiving their initial dose of sodium oxacillin 24 hours after surgery. J Antibiot (Tokyo), 1975 Apr, 28(4), 312 - 6 Streptomycylamines: difference in activity and mode of action between short-chain and long-chain derivatives; Heding H et al.; A homologue series of aliphatic streptomycylamines (SM-amines) have been prepared and tested in vitro (binding to 70S ribosomes) and in vivo (MIC) . The short-chain SM-amines act as streptomycin (SM) but are less active than SM . They are inactive towards a SM-resistant Escherichia coli, our strain 042 . The long-chain SM-amines are active both towards our sensitive and resistant E . coli, our strains 079 and 042 . Their activities are not pH-dependent in contrast to that of SM . However, the higher homologues of the aliphatic amines (C10 Congruent TO C10) are considerably active per se although two to four times less than the corresponding SM-amines . Further, the amines do not compete with the SM-amine for the binding to the ribosomal particles . The binding affinities of these long-chain SM-amines to ribosomes are considerably smaller than that of SM . The binding is however specific as a typical isotope dilution curve can be obtained . We conclude that the long-chain SM-amines have a mode of action different from that of SM. J Gen Microbiol, 1975 Apr, 87(2), 351 - 8 Polyene sensitivity during germination of conidia of Aspergillus fumigatus; Russell NJ et al.; A system for the rapid and relatively synchromous germination of conidia from a clinical isolate of Aspergillus fumigatus is described . The polyene-mediated release of K plus from germinating conidia has been determined . Ungerminated conidia were insensitive to amphotericin B methyl ester (AME) at concentrations greater than 50 mug/ml, but rapidly became sensitive to 1 to 2 mug AME/ml during the intitial stages of germination . These findings have been correlated with minimum inhibitory concentration values obtained in studies of conidial germination and hyphal outgrowth using a variety of growth tests. J Pediatr, 1975 Apr, 86(4), 617 - 20 Hemophilus influenzae type B susceptibility to 17 antibiotics; Emerson BB et al.; One hundred and one strains of Hemophilus influenzae type b isolated at the Children's Hospital Medical Center from blood or CSF and 18 strains known to be resistant to ampicillin of which 17 were supplied to us by others were tested for their sensitivity to 17 antibiotics . Two groups were defined according to their sensitivity to ampicillin . When 10-3 bacteria were applied, 18 strains isolated from patients with ampicillin treatment failures had a median minimum inhibitory concentrations of 3.1 mug/ml . At 10-6 bacteria the median MIC for the resistant strains increased 512-fold, whereas the sensitive strains increased two-fold . The most active antibiotics against sensitive and resistant strains were rifampin, chloramphenicol, gentamicin, rosamycin, and erythromycin with MICs ranging from 0.2-0.8 mug/ml at 10-3 bacteria and from 0.2-1.6 mug/ml at 10-6. Cancer Res, 1975 Mar, 35(3), 554 - 9 Subcellular fate of protein antibiotic neocarzinostatin in culture of a lymphoid cell line from Burkitt's lymphoma; Maeda H et al.; 14C-LABELED PROTEIN ANTIBIOTIC NEOCARZINOSTATIN (NCS) was prepared efficiently by chemical modification . With the use of lymphoma-derived cell line P3HR-1, the subcellular behavior of this antitumor antibiotic was studied by the uptake a . nd autoradiography of isolated nuclei of radioactive NCS . The antibiotic was taken up by the cells, reaching the maximum value at 1.5 hr and decreasing in value at 4.0 hr to the level at 0.5 hr . The silver grains in the autoradiograms were also found in the isolated nuclei . The grain count in the nuclei showed a tendency similar to the uptake of NCS by the whole cells, i.e., a gradual increase at 0.5 hr, reaching the maximum value at 1.5 hr, and then decreasing after 4.0 hr to the level at 0.5 hr . These facts indicated that NCS reached not only to cytosol but also into the nucleus, and/or at least to the nuclear membrane of the lymphoid cell . The number of NCS molecules incorporated into the cells at 1.5 hr was calculated to be about 1 x 10-6/cells at a concentration of 3 mug NCS per ml of medium, which can be extrapolated to 1 x 10-4 molecules per cell at the minimum inhibitory concentration . The number of molecules should be even less within the nucleus . In cell-free systems, the interaction of DNA and NCS, which is an inhibitor of DNA synthesis, was investigated with use of a Sephadex G-100 column, with negative results . In the cell culture system, NCS molecules were degraded into smaller polypeptides of certain sizes by proteolysis either by serum component(s) or by cells themselves . An inactive isomer, pre-NCS, which is an antagonist of NCS and a partially denatured homologous molecule, behaved similarly to NCS in all of these experiments . Because the chemically modified NCS used in this study retained biological activity essentially similar to that of parental NCS, the results obtained here could be interpreted as similar to those of parental NCS in vitro. Antibiotiki, 1975 Mar, 20(3), 262 - 6 {Level of "internal" resistance of E . coli cultures to benyzlpenicillin}; Rezvan SP et al.; Interaction of benzylpenicillin inactivation by beta-lactamase and the growth of E . coli in the presence of various antibiotic concentrations was studied . It was found that penicillin inactivation began immediately after addition of the culture to the medium in spite of the fact that the number of the viable cells at that time decreased . The culture began to multiply only when benzylpenicillin concentration in the medium lowered up to a definite level (6-7 gamma/ml) . Such a concentration must determine the level of the "inner" culture resistance to benzylpenicillin, not connected with the beta-lactamase effect . Moreover, the "inner" resistance proved to be the same for the cultures of E . coli, markedly differing by the amounts of beta-lactamase produced and the resistance levels to benzylpenicillin . Therefore, the routine method for determination of the "inner" resistance of the beta-lactamase-producing cultures to penicillins, using low innoculation doses produced higher results as compared to the real "inner" resistance . Significant differences observed between the values of the "inner" resistance (6-7 gamma/ml) and the MIC of benzylpenicillin at high innoculation doses with respect to E . coli 2 (129 gamma/ml) and E . coli 82 (15000 gamma/ml) may probably be explained by destruction of the drug by beta-lactamase. Transplantation, 1975 Feb, 19(2), 166 - 9 A modified rosette inhibition test in renal allotransplantation; Cantaluppi A et al.; The rosette inhibition test, with a modification of the technique which enables highly accurate marking of T lymphocytes, has been employed in the followup of 55 renal transplant patients . The minimal inhibitory concentration of antilymphocyte globulin (that is, that concentration of antilymphocyte globulin causing 25% inhibition of rosette formation) was higher than 1:16,000 in 63 (97%) of 65 separate determinations made during acute rejection episodes, and lower than 1:16,000 in 377 (92%) of 410 determinations after which no clinical evidence of rejection developed . The results presented in this paper indicate that this modified test is a useful tool either to predict the occurrence of or to confirm the diagnosis of rejection. Arzneimittelforschung, 1975 Feb, 25(2), 234 - 7 The parenteral application of a new metacycline preparation, tri-metacycline; Kahan IL et al.; Tri-metacycline, one of the new tetracycline complexes (tritetracyclines), is prepared by mere dissolution of metacycline hydrochloride in an aqueous solution of the complexing agent . In vitro and in vivo studies show a high antibiotic activity . Significantly lower MIC values were found for tri-metacycline than for the parent compound . Parenteral administration resulted in high sera and tissue values, without signs of accumulation; excretion via the kidneys was proved. J Infect Dis, 1975 Feb, 131(2), 158 - 62 Pharmacokinetics of gentamicin sulfate in bronchial secretions; Pennington JE et al.; Dogs were used as a model for the study of the rate of appearance, peak concentrations, and rate of clearance of gentamicin sulfate in bronchial secretions . Gentamicin (dose, 1.7 mg/kg) was given by rapid intravenous infusion, by intramuscular injection, or as two divided intramuscular injections with a 4-hr interval . Intravenous infusion resulted in the highest bronchial concentrations of gentamicin, but the drug was cleared from the respiratory secretions in approximately 3 hr . In contrast, intramuscular injections gave low but more sustained bronchial leves of the drug . The time during which bronchial gentamicin concentrations exceeded a particular minimal inhibitory concentration for a susceptible bacterium such as Pseudomonas was related to the method of drug administration . Thus, to achieve the maximal antibiotic effectiveness, the minimal inhibitory concentraiton of gentamicin for the microorganism should be considered when the dose or frequency of parenteral gentamicin is prescribed. Chemotherapy, 1975, 21(6), 358 - 66 Experimental and clinical studies of 5-fluorocytosine activity in Candida ocular infections . I . In vitro activity of 5-fluorocytosine on Candida species isolated from ocular infections; Segal E et al.; In vitro sensitivity to 5-fluorocytosine (5-FC) of 35 Candida strains (14 C . albicans, 10 C . tropicalis, 5 C . parapsilosis, 2 C . guilliermondii, 2 C . krusei, 2 C . pseudotropicalis), isolated from the eyes of patients suffering from various external ocular inflammations who had not been treated with 5-FC, was tested and compared to that of standard Candida species . The minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of 5-FC for the strains isolated from ocular infections ranged from 0.06 to 1.95 mug/ml and from 0.24 to 7.81 mug/ml, respectively, indicating that no primary resistant strains to 5-FC were found in this series. Antibiotiki, 1975 Jan, 20(1), 62 - 6 {Sensitivity of certain strains of pathogenic Leptospira to streptomycin, the nature of resistant variants and the frequency of their occurrence}; Petrov EM et al.; Streptomycin sensitivity of 112 Leptospira strains isolated from domestic and wild animals was studied . Independent of the isolation period and nature the strains proved to be highly sensitive to the antiobiotic (MIC 0.1 to 0.5 gamma/ml) . On the example of a clone strain of Leptospira it was shown with a fluctuation test that streptomycin resistance occurred spontaneously . Frequency of the streptomycin resistant mutations was determined for 5 clone strains of L . interrogans . It was 10-9 to 10-7 per a Leptospira. Proc Eur Dial Transplant Assoc, 1975, 11, 320 - 5 A modified rosette inhibition test in the early diagnosis of renal allograft rejection; Cantaluppi A et al.; The rosette inhibition test has been employed in the follow-up of 30 renal transplant patients using a technique which enables highly accurate marking of T-lymphocytes . The minimal inhibitory concentration (MIC) of anti-lymphocyte globulin (ALG) - that is, that concentration of ALG causing 25% inhibition of rosette formation-was higher than 1/16,000 in 32 (97%) out of 33 separate determinations made two to six days befor rejection became clinically evident, and lower than 1/16,000 in 323 (92%) out of 351 determinations after which no clinical evidence of rejection developed . The results presented in this paper indicate that this modified test is a useful tool either to predict the occurrence of or to confirm the diagnosis of rejection. Scand J Infect Dis, 1975, 7(4), 259 - 64 Evaluation of the antibiotic effect of treatment of maxillary sinusitis; Carenfelt C et al.; As the effect of antibiotic treatment of maxillary sinusitis has been questioned, the elimination of bacteria from sinus secretions was studied during antibiotic treatment . Penicillin V, azidocillin, tetracycline or doxycycline was administered to 54 patients with maxillary sinusitis . Samples of sinus secretion were aspirated both before treatment and 2-3 days after the onset of treatment . When the antibiotic concentration was below the upper limit of MIC for sensitivity group 1, bacterial growth was present in practically all samples . When the antibiotic concentration equalled or was above this limit, there was no bacterial growth in about half of the samples . A prerequisite for antibiotic effect--elimination of bacteria--is that the antibiotic concentration is well above the MIC of the bacteria at the site of infection . The choice between bactericidal or bacteriostatic antibiotics appeared unimportant . Bacterial survival in the maxillary sinus despite a high antibiotic concentration in the sinus illustrates that MIC values determined in the laboratory do not always mirror the sensitivity of bacteria to antibiotics in vivo. Andrologia, 1974, 6(1), 45 - 52 Mycoplasmas in semen from fertile and infertile men; Friberg J et al.; PIP: Mycoplasma cultures were obtained from ejaculates of 50 men in couples whose infertility remained unexplained after comprehensive testing of both partners, from 32 men with high serum titres (71:32) of sperm-agglutinating antibodies whose wives were apparently normal, and from 32 men without sperm-agglutinating antibodies whose wives were pregnant . 2 sperm samples were obtained from each of the men and cultures were also obtained from 38 of the wives in couples with unexplained infertility . T-mycoplasmas were cultured from 38 of the 50 ejaculates (76%) of men with unexplained infertility . When results of the isolations of T-mycoplasmas from both husbands and wives were compiled, T-mycoplasmas were isolated from 40 of the couples (80%) . T-mycoplasmas were found in 15 of the 32 men with high serum titres (47%) and in 6 of the recent fathers (19%) . The minimal inhibitory concentration (MIC) of doxycycline was determined for a total of 39 T-mycoplasma isolates; the majority were sensitive to concentrations of .03 mcg/ml or less . Doxycycline 200 mg on the 1st day followed by 100 mg daily for another 9 days, cyclically from the 7th to the 16th day of the menstrual cycle, was given to both partners of the infertile couples from whom T-mycoplasmas were isolated . 9 pregnancies were reported among the 40 couples . 14 men with T-mycoplasma infections and high serum titres of sperm agglutinating antibodies were treated with 200 mg doxycycline daily for 3 months to establish whether eradication of the mycoplasmas would affect the serum titre of antibodies . 1 pregnancy was reported in the group but no change in the titre of sperm-agglutinating antibodies in the serum or the degree of agglutination in the ejaculate was observed in any of the men . After 3 months of treatment, ejaculates from 31 of the men were cultured and found to be negative . The findings support recent studies suggesting an association between T-mycoplasma infection and infertility .
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