Showing papers on "Penicillin published in 1977"
TL;DR: It is shown that penicillins bind to all six proteins but that at least some cephalosporins fail to bind, or bind very slowly, to proteins 2, 5 and 6, although they bind to the other proteins.
Abstract: Benzyl[14C]penicillin binds to six proteins with molecular weights between 40000 and 91000 in the inner membrane of Escherichia coli. Two additional binding proteins with molecular weights of 29000 and 32000 were sometimes detected. All proteins were accessible to benzyl[14C]penicillin in whole cells. Proteins 5 and 6 released bound benzyl[14C]penicillin with half times of 5 and 19 min at 30 degrees C but the other binding proteins showed less than 50% release during a 60-min period at 30 degrees C. The rate of release of bound penicillin from some of the proteins was greatly stimulated by 2-mercaptoethanol and neutral hydroxylamine. Release of benzyl[14C]penicillin did not occur if the binding proteins were denatured in anionic detergent and so was probably enzymic. No additional binding proteins were detected with two [14C]cephalosporins. These beta-lactams bound to either all or some of those proteins to which benzyl[14C]penicillin bound. No binding proteins have been detected in the outer membrane of E coli with any beta-[14C]lactam. The binding of a range of unlabelled penicillins and cephalosporins were studied by measuring their competition for the binding of benzyl[14C]penicillin to the six penicillin-binding proteins. These results, together with those obtained by direct binding experiments with beta-[14C]lactams, showed that penicillins bind to all six proteins but that at least some cephalosporins fail to bind, or bind very slowly, to proteins 2, 5 and 6, although they bind to the other proteins. Since these cephalosporins inhibited cell division and caused cell lysis at concentrations where we could detect no binding to proteins 2, 5 and 6, we believe that these latter proteins are not the target at which beta-lactams bind to elicit the above physiological responses. The binding properties of proteins 1, 3, and 4 correlate reasonably well with those expected for the above killing targets.
671 citations
TL;DR: In this article, three cases of meningitis and two cases of septicaemia were caused by pneumococci resistant to the penicillins/cephalosporins and chloramphenicol.
296 citations
TL;DR: Tolerance is a common, clinically important form of penicillin resistance, that differs from previously described forms of pencillin resistance,that due to beta-lactamase, and that due to "intrinsic" (e.g., methicillin resistant) mechanisms.
292 citations
TL;DR: A girl aged 12 developed pseudomembranous colitis after a short course of oral penicillin, and no pathogenic bacteria, mycoplasmas, or viruses were found in her faeces, but they did contain a toxin.
Abstract: A girl aged 12 developed pseudomembranous colitis after a short course of oral penicillin. She had no history of adverse reaction to penicillin before or after the illness. No pathogenic bacteria, mycoplasmas, or viruses were found in her faeces, but they did contain a toxin. Toxin was also found in four of five other patients with pseudomembranous colitis but not in six specimens obtained from patients with diarrhoea caused by other disorders. Further studies may show that pseudomembranous colitis is caused by a bacterial toxin.
219 citations
TL;DR: The persistent effects of penicillin G and erythromycin were directly related to duration of exposure and concentration of drug, up to a point of maximal response.
Abstract: Persistent suppression of bacterial growth by certain antibiotics was tested by periodic counts of viable organisms in a culture of Staphylococcus aureus that had been incubated in media containing drugs for limited periods of time and then removed by centrifugation. During short (2 hr) periods of exposure of test cultures to penicillin G, cephalothin, erythromycin, clindamycin, vancomycin, and tetracyline, effects on the growth of S. aureus were produced that persisted after removal of the drug for periods of 1.7-4.1 hr. A persistent antibiotic effect was not observed with gentamicin. The persistent effects of penicillin G and erythromycin were directly related to duration of exposure and concentration of drug, up to a point of maximal response. The maximal durations of bacterial suppression after exposure to penicillin G and erythromycin were approximately 2 and 5 hr, respectively. These effects were observed over a wide range of inocula.
189 citations
Abstract: A multicenter cooperative study of almost 3,000 patients by members of the Penicillin Study Group of the American Academy of Allergy has confirmed the usefulness of skin tests to penicillin G (Pen G) and penicilloyl-polylysine (PPL) in the evaluation of penicillin hypersensitivity. Nineteen percent of 1,718 patients with a history of penicillin allergy had positive skin tests to either or both agents, vs 7% of 1,229 patients with no such history. Among patients with a history of penicillin allergy where a detailed history was available, positive skin tests were noted in 46% with a history of anaphylaxis, 17% with a history of urticaria or angioneurotic edema, and 7% with a history of a maculopapular reaction. PPL Generally gave somewhat higher reaction rates than Pen G, but both skin tests were needed to elicit the maximum number of reactors. After skin tests were completed, 379 patients were challenged with penicillin. Six percent of patients with a positive history had an allergic reaction vs 2% of patients with a negative history. However, 67% of the 9 challenged patients with a positive skin test had an allergic reaction, and half of these were immediate or early systemic reactions. Only 3% of the 346 challenged patients with a negative skin test had a reaction to challenge and only one fourth of these had early reactions thought to be possibly mediated by IgE.
175 citations
01 Jan 1977
TL;DR: A multicenter cooperative study of almost 3,000 patients by members of the Penicillin Study Group of the American Academy of Allergy has confirmed the usefulness of skin tests to penicillin G (Pen G) and penicilloyl-polylysine (PPL) in the evaluation ofpenicillin hypersensitivity.
Abstract: A multicenter cooperative study of almost 3,000 patients by members of the Penicillin Study Group of the American Academy of Allergy has confirmed the usefulness of skin tests to penicillin G (Pen G) and penicilloyl-polylysine (PPL) in the evaluation of penicillin hypersensitivity. Nineteen percent of I, 718 patients with a history of penicillin allergy had positive skin tests to either or both agents, vs 7% of 1,229 patients with no such history. Among patients with a history of penicillin allergy where a detailed history was available, positive skin tests were noted in 46% with a history of anaphylaris, 17% with a history of urticaria or angioneurotir edema, and 7% with a history of a maculopapular reaction. PPL Generally gave somewhat higher reaction rates than Pen G, but both skin tests were needed to elicit the maximum number of reactors. After skin tests were completed, 379 patients were challenged with penicillin. Six percent of patients with a positive history had an allergic reaction vs 2% of patients with a negative history. However, 67% of the 9 challenged patients with a positive skin test had an allergic reaction, and half of these were immediate or early systemic reactions. Only 3% of the 346 challenged patients with a negative skin test had a reaction to challenge and only one ,fourth of these had early reactions thought to be possibly mediated by IgE.
172 citations
TL;DR: Penicillin G in the dosage studied is adequate therapy for most streptococcal and meningococcal meningitis in children; an increased dosage may be necessary when the minimal inhibitory concentration of penicillin to the etiologic agent is unusually high.
Abstract: We undertook a prospective study of the pharmacokinetics of penicillin G (administered intravenously every four hours for a total of b50,000 U per kilogram per day) in the cerebrospinal fluid of children with purulent meningitis. Both the absolute mean cerebrospinal-fluid penicillin concentration (0.8, 0.7 and 0.3 microgram per milliliter) and the percentage of the simultaneous serum penicillin concentration measurable in the cerebrospinal fluid (18.4, 9.9, 4.9 per cent) declined on the first, fifth and 10th days of therapy, respectively. A mean peak cerebrospinal-fluid penicillin concentration of 0.96 micrograms per milliliter was measured at least transiently on all three study days. This pharmacokinetic pattern correlated with the return of cerebrospinal-fluid protein concentration toward normal (P less than 0.01). Penicillin G in the dosage studied is adequate therapy for most streptococcal and meningococcal meningitis in children; an increased dosage may be necessary when the minimal inhibitory concentration of penicillin to the etiologic agent is unusually high.
129 citations
TL;DR: A retrospective analysis of 50 randomly selected patients, according to the Kunin's categories of use, showed 64% of total antibiotic therapy as not indicated or inappropriately administered in terms of drug or dosage.
Abstract: A study of antibiotic use at Duke University Medical Center in June 1973 showed that 34.2% of all patients received antibiotics (43.6% surgical, 21.4% medical patients). Cephalothins were most frequently ordered for surgical patients, ampicillin sodium and penicillin G or penicillin V with potassium for other patients. A retrospective analysis of 50 randomly selected patients, according to the Kunin's categories of use, showed 64% of total antibiotic therapy as not indicated or inappropriately administered in terms of drug or dosage. These results are similar to previous reports of antibiotic surveillance and further establish the need for continuing education of prescribing physicians. ( JAMA 237:2819-2822, 1977)
119 citations
TL;DR: The antibiotic “tolerance” of S. sanguis is interpreted in terms of the hypothesis that the activity of bacterial murein hydrolases is essential for the irreversible effects of cell wall inhibitors.
Abstract: In contrast to group A streptococci or Streptococcus pneumoniae, cells of Streptococcus sanguis (group H) do not exhibit the irreversible effects of penicillin treatment, such as loss of viability or lysis. On the other hand, the same bacteria show typical effects of penicillin, such as morphological alterations, reduction in the rate of cell wall synthesis, and secretion of murein and lipoteichoic acid polymers into the medium. A novel effect of cell wall inhibitors was also noted: treatment with beta-lactams or with fosfomycin, d-cycloserine, or beta-halogeno-d-alanine caused the release of substantial amounts of glycerol lipids into the growth medium. The antibiotic “tolerance” of S. sanguis is interpreted in terms of the hypothesis that the activity of bacterial murein hydrolases is essential for the irreversible effects of cell wall inhibitors.
110 citations
TL;DR: A clinical review of patients from whom the β-lactamase-producing strains of B. melaninogenicus were isolated did not suggest any increased virulence in these strains or an unexpectedly poor clinical response to appropriate therapy, and the specific amount produced correlated only partially with penicillin MIC values.
Abstract: The minimum inhibitory concentrations (MIC) of penicillin and six other antimicrobials were determined for 50 clinical isolates of Bacteroides melaninogenicus. Agar dilution susceptibilities were performed using supplemented brucella blood agar and the proposed National Committee for Clinical Laboratory Standards standard method for anaerobes; results with the two methods were comparable. A penicillin concentration >/=0.8 mug/ml was needed to inhibit 56% of the isolates, whereas 100% were susceptible to 0.1 mug of clindamycin per ml. All isolates with penicillin MIC values >/=0.8 mug/ml produced beta-lactamase using a slide method. A micro-iodometric assay was used to quantitate beta-lactamase production in six isolates. The beta-lactamase activity of B. melaninogenicus was comparable to that of a Staphylococcus aureus isolate but was not inducible, and the specific amount produced correlated only partially with penicillin MIC values. A clinical review of patients from whom the beta-lactamase-producing strains of B. melaninogenicus were isolated did not suggest any increased virulence in these strains or an unexpectedly poor clinical response to appropriate therapy.
TL;DR: Treatment of abscesses of the central nervous system should be considered according to the site and the likely antecedent cause, and multiple therapy is appropriate while awaiting the bacteriological results.
Abstract: Samples of intracranial pus and serum from 32 patients were assayed to determine the concentrations reached in them of penicillin, ampicillin, cloxacillin, cephaloridine, gentamicin, chloramphenicol, fusidic acid, and lincomycin. Metronidazole had not been given. Penicillin penetrated abscesses reasonably well, but other beta-lactam antibiotics did not. The penetration of chloramphenicol was erratic. Aminoglycosides penetrated poorly, but lincomycin and fusidic acid penetrated well. Assay of sulphonamides and co-trimoxazole in pus was unreliable. These studies indicate that treatment of abscesses of the central nervous system should be considered according to the site and the likely antecedent cause. Abscesses of sinusitic origin, usually in the frontal lobe, yield penicillin-sensitive streptococci. Penicillin is the drug of choice. Abscesses of otitic origin, usually in the temporal lobe, yield a mixed flora, often including anaerobic bacteria. Multiple antibiotic therapy is indicated. Abscesses of metastatic or cryptogenic origin yield streptococci or mixed cultures, and multiple therapy is appropriate while awaiting the bacteriological results. Spinal and post-traumatic abscesses yield Staphylococcus aureus, and fusidic acid is the drug of choice.
TL;DR: A comparison with isolates of enterococci obtained in 1968 revealed that there has been a decrease in prevalence of high-level resistance among organisms isolated from wound cultures in 1976, however, no decrease in resistance to streptomycin or kanamycin was demonstrated among blood or urine isolates.
Abstract: Two hundred and three recent clinical isolates of enterococci were tested for susceptibility to streptomycin, kanamycin, amikacin, gentamicin, sisomicin, and tobramycin. Depending upon the source of the isolate, 36 to 54% of the enterococci demonstrated high-level resistance (minimal inhibitory concentration, >2,000 μg/ml) to streptomycin, 16 to 49% to kanamycin, and 0 to 14% to amikacin. None of the strains was highly resistant to gentamicin, sisomicin, or tobramycin. A comparison with isolates of enterococci obtained in 1968 revealed that there has been a decrease in prevalence of high-level resistance among organisms isolated from wound cultures in 1976. However, no decrease in resistance to streptomycin or kanamycin was demonstrated among blood or urine isolates. Penicillin, combined with gentamicin, sisomicin, or tobramycin, was synergistic against all 10 strains of Streptococcus faecalis subjected to formal testing. For streptomycin and kanamycin, the presence or absence of synergism with penicillin correlated with the absence or presence of high-level aminoglycoside resistance. High-level resistance to amikacin was seen in only 1 of the 10 strains. Nonetheless, combinations of penicillin plus amikacin failed to produce synergistic killing against 6 of the 10 strains. Indeed, the combination was synergistic only against those four strains that were susceptible to high levels of kanamycin.
TL;DR: Some of the earliest animal studies of antimicrobial toxicity of this type were those of penicillin in guinea pigs, and it was noted that oral or ip administration of 20,000-100,000 units of Penicillin produced lethargy, failure to feed, and death in Guinea pigs.
Abstract: Some of the earliest animal studies of antimicrobial toxicity of this type were those of penicillin in guinea pigs. DeSomer et al. [12] noted that oral or ip administration of 20,000-100,000 units of penicillin produced lethargy, failure to feed, and death in guinea pigs. The pathologic find
TL;DR: Mezlocillin is a new semisynthetic penicillin that inhibited 71% of the isolates of Serratia marcescens, 67% of Escherichia coli, 50% of Enterobacter spp.
Abstract: Mezlocillin is a new semisynthetic penicillin that inhibited 71% of the isolates of Serratia marcescens , 67% of Escherichia coli , 50% of Enterobacter spp., and 49% of Klebsiella spp. at a concentration of 12.5 μg/ml. It is also active against both indole-positive and -negative Proteus spp. and gram-positive cocci, except penicillin G-resistant Staphylococcus aureus . At a concentration of 100 μg/ml, it inhibited 94% of the isolates of Pseudomonas aeruginosa . It is more active than ampicillin, carbenicillin, and cephalothin against some gram-negative bacilli.
TL;DR: It is determined that isolates of Neisseria gonorrhoeae from patients with disseminated gonococcal infection (DGI) are different from randomly collected isolates from Patients with uncomplicated (local) disease.
Abstract: We have determined that isolates of Neisseria gonorrhoeae from patients with disseminated gonococcal infection (DGI) are different from randomly collected isolates from patients with uncomplicated (local) disease. Our comparison was based on the six phenotypic properties of: sensitivity to penicillin (PenS), erythromycin, and streptomycin; resistance to the bactericidal effects of pooled human sera; requirements for arginine, hypoxanthine, and uracil (AHU-); and sensitivity to toxic agar. Although the marked association among these traits made analysis difficult, several factors independently related to virulence were defined. The DGI isolates were significnatly more PenS and resistant to serum, even when the other variables were held constant. An apparent correlation between AHU- auxotype and virulence was shown to be due to the PenS property of most AHU- isolates. Thus, certain mutations to antibiotic resistance as well as susceptibility to sera, may result in loss of virulence in the gonococcus, perhaps through alteration of cell envelope structure.
TL;DR: The same concentrations of tetracycline, rosamicin, erythromycin, and chloramphenicol were sufficient to inhibit C. trachomatis inclusion formation, and an increased concentration of sulfisoxazole was often needed to inhibit inclusion formation.
Abstract: Minimum inhibitory concentrations of several antibiotics and a sulfonamide for growth of the 15 known immunotypes of Chlamydia trachomatis were determined in HeLa 229 cell cultures. The concentrations for complete inhibition of infectious-organism production were (per milliliter): tetracycline, 0.02 to 0.5 μg; rosamicin, 0.05 to 0.25 μg; erythromycin, 0.1 to 0.5 μg; chloramphenicol, 10 μg; penicillin, 0.02 to 50 U; ampicillin, 0.1 to 50 μg; and sulfisoxazole, 2 to 200 μg. The same concentrations of tetracycline, rosamicin, erythromycin, and chloramphenicol were sufficient to inhibit C. trachomatis inclusion formation. An increased concentration of sulfisoxazole was often needed to inhibit inclusion formation. Penicillin at 100 U/ml and ampicillin at 100 μg/ml failed to completely inhibit inclusion formation.
TL;DR: Findings have implications for the combined clinical use of N-acetylcysteine and aerosolized antibiotics and are also important for the processing of sputum specimens in the microbiology laboratory.
Abstract: The antibiotic bacerial inactivity of N-acetylcysteine (NAC) and its interaction with penicillin and aminocyclitol antibiotics was evaluated. NAC inhibited growth of both gram-negative and gram-positive bacteria. Strains of Pseudomonas aeruginosa were more susceptible than other microorgainsms tested. P. aeruginosa strains were inhibited synergistically by NAC and carbenicillin or ticarcillin. However, NAC antagonized the activity of gentamicin and tobramycin. These findings have implications for the combined clinical use of NAC and aerosolized antibiotics and are also important for the processing of sputum specimens in the microbiology laboratory.
Journal Article•
TL;DR: The degree of resistance reported here is relative and does not necessarily preclude successful treatment with full therapeutic doses of penicillin G, butpenicillin preparations that give low blood concentrations may not be suitable for treating infections caused by these strains.
Abstract: 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.
TL;DR: Six strains of Staphylococcus aureus resistant to semisynthetic penicillins were recovered from clinical sources during a two-month period and each was resistant to oxacillin at low inocula.
Abstract: Six strains of Staphylococcus aureus resistant to semisynthetic penicillins were recovered from clinical sources during a two-month period. Resistance was detected by standard disk sensitivity tests at 37 C. Two resistant strains were responsible for infections (one of which was fatal), and five strains were susceptible only to phage type 92. All of the strains produced penicillinase, which did not destroy oxacillin, and each was resistant to oxacillin at low inocula. Relative resistance to cephalosporin was demonstrable by the tube dilution assay but not by standard disk tests. The strains susceptible to phage type 92 were susceptible to vancomycin and to the synergistic action of oxacillin or cephalothin plus gentamicin.
TL;DR: These laboratory findings confirmed the clinical observations in these two patients that penicillin-streptomycin therapy should be used in vitamin B6-dependent streptococcal endocarditis and must be considered in patients with suggestive clinical findings but negative blood cultures.
Abstract: Vitamin B6-dependent viridans streptococci were isolated from two patients with microbial endocarditis. Because of their unique requirement for pyridoxal hydrochloride, these organisms did not grow normally in the media usually used in diagnostic laboratories. When tested in supplemented media, both strains were resistant to penicillin G and relatively sensitive to streptomycin. Penicillin-streptomycin synergy was demonstrated in vitro as well as in experimental endocarditis. These laboratory findings confirmed the clinical observations in these two patients that penicillin-streptomycin therapy should be used in vitamin B6-dependent streptococcal endocarditis. Nutritionally varient streptococci may be important pathogens in microbial endocarditis and must be considered in patients with suggestive clinical findings but negative blood cultures.
TL;DR: It is suggested that the effect of inactivating human pus may be an intrinsic property of the host, which should be investigated further as it has important implications for clinical practice.
Abstract: Four of 22 specimens of human pus inactivated up to 90% of added penicillin within one hour in vitro. Ampicillin and cephaloridine were also inactivated, but streptomycin and fusidic acid were not. The effect was not related to the protein content of the pus, nor to its pH value. Microbes that may produce beta-lactamase in small quantities were isolated from three of the four specimens, but the enzyme was not detected in the pus by physical methods nor by microbiological inhibition assay. The inactivating effect was shown to be a property of the solid portion of the pus, and was absent from the filtrate. We suggest that the effect may be an intrinsic property of the host, which should be investigated further as it has important implications for clinical practice.
TL;DR: T-1220 is a new semisynthetic penicillin derivative that possesses a broad spectrum of in vitro antibacterial activity against gram-positive and gram-negative bacteria and is more effective than carbenicillin (CB-PC) against Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus species, and Serratia marcescens.
Abstract: T-1220, sodium 6-[d-(-)-α-(4-ethyl-2,3-dioxo-1-piperazinylcarbonyl-amino)- α-phenylacetamido] penicillanate, is a new semisynthetic penicillin derivative that possesses a broad spectrum of in vitro antibacterial activity against gram-positive and gram-negative bacteria. T-1220 is more effective than carbenicillin (CB-PC) against Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus species, and Serratia marcescens. Addition of human serum to culture media did not significantly alter the antibacterial activity of T-1220. Greater bactericidal activity toward various strains of gram-negative bacteria was demonstrated with T-1220 than with CB-PC. T-1220, like penicillin G, was hydrolyzed by penicillinase, but was sable to a type IV penicillinase produced by P. aeruginosa strains. In vivo antibacterial activities of T-1220, ampicillin (AB-PC), and CB-PC were compared, using systemic infections of mice with P. aeruginosa, K. pneumoniae, and Escherichia coli. The 50% effective doses (milligrams per kilogram) of T-1220 were consistently lower than those of AB-PC and CB-PC.
TL;DR: Therapy for pelvic inflammatory disease must be empirical since it is impossible to distinguish clinically between gonococcal and nongonococcal infection, and data indicate that both regimens recommended by the Center for Disease Control are equally effective in producing clinical cure.
Abstract: To evaluate guidelines for outpatient treatment of acute pelvic inflammatory disease recommended by the Center for Disease Control we studied 197 afflicted women. The women were treated either with tetracycline or with procaine penicillin and ampicillin, and 92 per cent were subsequently seen at least once to assess efficacy of clinical and microbiologic treatment. Neisseria gonorrhoeae was isolated from the lower genital tract in 68 per cent of these women, and although they had a quicker symptomatic response than those with nongonococcal infection (P<0.01), the two regimens were equally effective in producing clinical cure. However, subsequent identification of a pelvic abscess was 10 times more common in women from whom N. gonorrhoeae was not isolated. Therapy for pelvic inflammatory disease must be empirical since it is impossible to distinguish clinically between gonococcal and nongonococcal infection, and our data indicate that both regimens recommended by the Center for Disease Control are...
TL;DR: Since metronidazole is only active against obligate anaerobic bacteria it is concluded that these organisms are the important pathogens in acute dental infections.
TL;DR: For several reasons, including the appearance of β-lactamase-producing gonococci, it is no longer clear that penicillin G is the "drug of choice" for gonorrhea.
Abstract: Spectinomycin and tetracycline are alternative drugs to penicillin in the treatment of gonorrhea. To compare the efficacy of these agents and their propensity to select resistant gonococci, we treated 4043 patients randomly with either 2 or 4 g of spectinomycin once or 9 g of oral tetracycline for four days. Minimum cure rate for anogenital gonorrhea was 94 per cent with either drug. Oropharyngeal infection responded poorly to spectinomycin in men, with failure of therapy in six of 11. Postgonococcal urethritis in men was less common after tetracycline than after spectinomycin (P<0.005). Spectinomycin failure was not related to drug resistance. Tetracycline failure correlated with resistance (P<0.0002); one fifth of the isolates resistant to 1.0 μg per milliliter of tetracycline were not eradicated. For several reasons, including the appearance of β-lactamase-producing gonococci, it is no longer clear that penicillin G is the "drug of choice" for gonorrhea. Spectinomycin and tetracycline are equa...
TL;DR: The activity of azlocillin, a new semisynthetic penicillin, was determined against 582 clinical isolates of gram-negative bacilli and gram-positive cocci and was more active than mezLocillin, ticarcillin, and carbenicillin and as active as BLP-1654 against isolate of P. aeruginosa.
Abstract: The activity of azlocillin, a new semisynthetic penicillin, was determined against 582 clinical isolates of gram-negative bacilli and gram-positive cocci. Over 75% of the isolates of Pseudomonas aeruginosa were inhibited at a concentration of 12.5 μg or less per ml. Azlocillin is also active against indole-negative and -positive Proteus spp., inhibiting 98 and 71%, respectively, at a concentration of 12.5 μg or less per ml. Isolates of Klebsiella spp. and Enterobacter spp. showed less susceptibility than isolates of Escherichia coli and Serratia spp. Gram-positive cocci except penicillin G-resistant Staphylococcus aureus were susceptible to azlocillin. Azlocillin failed to inhibit the growth of gram-negative bacilli when large inocula were used. It was more active in alkaline pH, but the type of medium used had little effect on its activity. Azlocillin was more active than mezlocillin, ticarcillin, and carbenicillin and as active as BLP-1654 against isolates of P. aeruginosa. It was not as active as mezlocillin against the majority of the other gram-negative bacilli.
TL;DR: After 4 h of continuous intravenous infusion, cefamandole reached concentrations in both brain and CSF in excess of the minimal bactericidal concentration for the test organism and compared favorably with ampicillin and penicillin in achieving bacteriological cure.
Abstract: Because cerebrospinal fluid (CSF) antibiotic levels fail to predict either clinical success or relapse in the treatment of bacterial meningitis, we examined simultaneous antibiotic concentrations in the blood, brain, and CSF of control rabbits and of animals with experimental pneumococcal meningitis. Cefamandole pharmacokinetics were analyzed in detail and compared with those of cephalothin, ampicillin, penicillin G, and tobramycin. After 4 h of continuous intravenous infusion, cefamandole reached concentrations in both brain and CSF in excess of the minimal bactericidal concentration for the test organism and compared favorably with ampicillin and penicillin in achieving bacteriological cure. Cephalothin levels in the central nervous system remained undetectable in both control and infected animals during this time. Tobramycin concentrations were measurable in the CSF, but not in brain tissue in association with an inflammatory stimulus.