Intravenous solutions of amphotericin B in 5% dextrose water with or without hydrocortisone or heparin demonstrated no appreciable loss of activity when exposed to fluorescent light for up to 24 h at 25 C (room temperature).

The deterioration of carbenicillin is similar to that of other penicillins. Susceptibility test results, by using disks which have been exposed to humidity, may indicate false resistance. Proper storage and handling methods are suggested.

Transduction of resistance to isoniazid and streptomycin as well as susceptibility to isoniazid in Mycobacterium smegmatis SN2 has been demonstrated. A method has been described for the selection of isoniazid-susceptible variants after transduction of susceptibility.

The minimal inhibitory concentrations of Virazole against 32 mean tissue culture infective doses of three type A influenza strains including type A/England/42/72 (H3N2) and a type B strain in tissue culture were 0.1 and 0.05 μg/ml, respectively. The growth inhibition pattern by various Virazole concentrations of type A virus was similar to that of the type B virus. Virazole appears to be slightly more potent against the A/England/42/72 strain than are other antiinfluenzal agents.

Staphylococcus aureus 462 is one of three bacteriocin-producing strains selected for study from 200 isolates of staphylococci of animal origin. These bacteriocins are specific in their activity, inhibiting the growth of certain strains of S. aureus and other gram-positive species, but not gram-negative organisms. Staphylococcin 462 was not found in significant concentrations in the supernatant fluid of broth cultures, nor was it released into the suspending liquid when the cells were mechanically disrupted. However, extraction of the cells with 7 M urea resulted in the liberation of much of the activity. The material was purified by gel permeation chromatography by using Sephadex G-200 and by preparative electrophoresis on polyacrylamide gels in the presence of sodium dodecyl sulfate. Chemical analysis showed that the material consisted of roughly 90% protein and 3% lipid. The molecular weight of sodium dodecyl sulfate-dissociated staphylococcin 462 was calculated to be about 9,000.

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Double-blind trials were conducted in volunteers to evaluate the efficacy of the prophylactic 3,4-dihydro-1-isoquinolineacetamide hydrochloride (DIQA) treatment against rhinovirus type 24 challenge. Ten men received a 7-day course of DIQA treatment and 11 men received a placebo. The intranasal viral challenge dose was 10 mean tissue culture infective doses. The oral administration of 1 g prechallenge and 2 g a day for 6 consecutive postchallenge days did not prevent the development of colds. Nine drug-treated men and 10 controls developed rhinovirus illness. However, the illnesses of the drug-treated men were mild. Rhinorrhea occurred less frequently and was more mild in the drug-treated group. The challenge virus was recovered from 80% of these subjects in both groups, but almost twice the number of challenge viruses were isolated from the controls than from the drug-treated men. The prophylactic DIQA therapy appears to suppress the cold syndrome and to reduce virus excretion, although its effect is marginal. Additional clinical trials are warranted to confirm the antirhinoviral effect of this drug.

The effect of rifampin on cutaneous hypersensitivity was studied in 11 tuberculous patients. A suppressive effect was noted in eight patients, five of whom developed a negative response to the strength of purified protein derivative to which they had been shown to be previously sensitive. In one instance complete anergy to purified protein derivative was noted. It appears that rifampin has immunosuppressive effects in some patients when used in conventional doses.

Gentamicin, an aminoglycoside antibiotic, occurs both free in the fermentation filtrate and bound to the mycelium of the producing organism, Micromonospora purpurea. The bound gentamicin, which represents the major portion of the total quantity present in the fermentation broth, was released after exposure to acid, alkali, or sonic disruption. Washing the mycelium with distilled water, heat treatment, and the addition of sodium chloride to the fermentation medium were not effective methods for releasing bound gentamicin. Gentamicin and other aminoglycoside antibiotics were effectively adsorbed from neutral aqueous solutions by the acid-extracted mycelium of M. purpurea. In addition, the acid-extracted mycelium of actinomycetes other than M. purpurea were shown to be able to adsorb gentamicin from solution.

During 1972 a large epidemic, in excess of 10,000 cases, of typhoid fever occurred in Mexico City, Pachuca, and other communities of Mexico. The main characteristic of the epidemic, in addition to the large number of persons affected, was the prevalence of a strain of Salmonella typhi which was highly resistant to chloramphenicol both in vivo and in vitro, and which belonged to a single phage type, Vi degraded approaching type A. Of 493 strains of S. typhi studied during the outbreak, 452 (91.7%) were resistant to chloramphenicol (CM), tetracycline (TC), streptomycin (SM), and sulfonamides (SU). The epidemic strain owes its resistance to an R factor which is easily transferable to Escherichia coli K-12 and which appears to be stable. In the third month of the outbreak, a strain of S. typhi resistant to CM, TC, SM, SU, ampicillin (AM), and kanamycin (KM) was isolated from a patient with severe typhoid fever. During the following 9 months, six additional strains of S. typhi resistant to AM, CM, TC, SM, and SU were also isolated. Transfer experiments to E. coli K-12 indicate that these strains are infected with two different R factors, one causing CM, TC, SM, and SU resistance and the other causing AM or AM and KM resistance. The frequency of transfer of the resistance in overnight crosses was in the order of 10−4 for CM, TC, SM, and SU and 10−6 for AM or AM, and KM. The appearance of these strains resistant both to chloramphenicol and ampicillin was a cause for concern for the clinicians; fortunately, they have remained an infrequent cause of disease.

Carbenicillin indanyl sodium, ampicillin, or cephalexin was administered orally to 61 patients with urinary tract infections. Assignment of drug was made by a computer-generated, randomized plan in a double-blind fashion. The rates of cure 4 weeks after therapy were 50, 42, and 50% for patients treated with carbenicillin, ampicillin, and cephalexin, respectively. Failure of therapy was correlated with chronicity of infection and sensitivity of the microorganism to the antibiotic used. Thirty-nine percent of the patients developed side effects, but there were no significant differences in side effects among the three antibiotics. This double-blind study demonstrates that carbenicillin indanyl sodium is as effective as ampicillin and cephalexin in treatment of urinary tract infections.

The in vitro susceptibility to BB-K8, butirosin, gentamicin, sisomicin, and tobramycin of seven groups of clinically significant gram-negative bacilli and Staphylococcus aureus was assessed by using the International Collaborative Study-World Health Organization criteria. The activity of gentamicin, sisomicin, and tobramycin generally paralleled each other. Sisomicin was the most potent compound by weight and usually demonstrated the most rapid rate of killing. BB-K8 and butirosin were less potent, but higher serum levels may be achieved with these agents. BB-K8 generally showed the greatest ratio between achieveable mean peak serum levels and concentrations needed to inhibit [Formula: see text] of each group of organisms tested. Additionally, BB-K8 was active against six of seven highly gentamicin-resistant strains. All of these antibiotics showed diminished activity at pH 6.4 but only gentamicin and sisomicin showed occasionally enhanced activity at pH 8.4.

Five volunteers received intramuscular injections of 7 mg (approximately 500 mg) of cephanone, a new cephalosporin for parenteral use per kg. Peak serum concentrations averaged 36 μg/ml, about four times as high as with the same doses of cephalothin, twice as high as with cephaloridine, and slightly lower than with cefazolin. With a constant intravenous infusion of 100 mg/h, a steady-state serum concentration of 31 μg/ml was attained in four volunteers. The serum half-life was similar for the intramuscular and intravenous studies, 2.4 and 2.6 h, respectively. Over 90% of the dose administered was recovered in the urine. The factor mainly responsible for the higher and more sustained serum concentrations of cephanone was its low renal clearance of 47 ml per min per 1.73 m2. Cephanone has a small apparent volume of distribution, probably related to its high serum protein binding of 88%.

Inhibition of the steady-state generation of Escherichia coli by the bacteriostatic antibiotic novobiocin is linearly related to drug concentration in the range of 0 to 30 μg/ml. Increased cell sizes result because the drug inhibits cell division. The generation rate dependence on drug concentration depends on the nonionized fraction of novobiocin and is invariant with inoculum size or medium composition. However, the antibacterial activity of novobiocin decreases as the concentration of nutrients and Mg2+ increases, although the inhibitory action of novobiocin on generation rate remains unchanged for concentrations of Mg2+ above 8.1 × 10−4 M. Novobiocin is synergistic in combinations with tetracycline in broth, but not when the Mg2+ was maintained at 4.05 × 10−3 M. Combinations of novobiocin with the 50S ribosomal subunit inhibitors chloramphenicol, erythromycin, or lincomycin are antagonistic, and the degree of growth inhibition is determined only by that component of the binary combination that would have the greater potency if it were acting alone.

Isolates (657) representing 22 bacterial species were tested for susceptibility to silver sulfadiazine. All of the strains tested were inhibited by concentration levels of the drug which are easily achieved topically. It is suggested that silver sulfadiazine may be useful as a broad-spectrum antimicrobial substance for the prevention and treatment of infections of burns and wounds.

The generation rate constants for the steady-state growth of antibiotic-inhibited Escherichia coli have the same formal dependency on concentration for deoxylincomycin, lincomycin (phase I), erythromycin, clindamycin, and U24729A. They may be kinetically classified as a group A, in which the first three compounds comprise a subgroup A1 and the latter two a subgroup A2. Generation rate constants initially decrease linearly with concentration but asymptotically approach zero at higher concentrations. With tetracycline or chloramphenicol, the generation rate decreases linearly with all concentrations, and these compounds may be kinetically classified as group B. Combining an antibiotic from group A with one from group B gives a response equal to that obtained with equivalent amounts of each antibiotic alone, and there are no significant effects from the order of antibiotic addition. However, combinations of an A1 with an A2 antibiotic are antagonistic, and there are significant effects from the order of addition. The dependencies of generation rate constants in the presence of these antibiotics can be rationalized by a receptor site model that considers varying degrees of the rate of drug transfer and drug inactivation in the organism.

The activities of trimethoprim (TMP) and sulfamethoxazole (SMZ), alone and in combination (SMZ-TMP), and of the following antibiotics were tested against 115 clinical isolates of nontyphoid Salmonella species: tobramycin, gentamicin, ampicillin, amoxicillin, neomycin, kanamycin, chloramphenicol, and tetracycline. The methods of disk diffusion, microtiter broth dilution, and agar dilution were employed for all single antimicrobial agents as well as for SMZ-TMP studies. Growth curves were performed in broth. SMZ-TMP, TMP, gentamicin, tobramycin, and neomycin were the most active drugs in vitro. All strains were inhibited by ≤1 μg of TMP per ml, but >100 μg of SMZ per ml was required for at least 10% of strains. SMZ and TMP in a ratio of 10:0.5, respectively, inhibited all isolates and were synergistic for 105 strains. All strains inhibited by the combination of 10:0.5 SMZ-TMP had a zone diameter of ≥22 mm by using a combination disk containing 1.25 μg of TMP and 23.75 μg of SMZ. Seven isolates were resistant to >100 μg/ml of ampicillin or amoxicillin; all isolates were sensitive to chloramphenicol at ≤6.3 μg/ml. SMZ-TMP appears to be active against nontyphoid salmonellae in vitro; this is usually due to a synergistic effect.

A patient with a history of alcoholism and drug abuse who developed Pseudomonas cepacia endocarditis is described. The organism was found to be resistant in vitro to all common antimicrobial agents except chloramphenicol and trimethoprim-sulfamethoxazole. Treatment failed with penicillin and streptomycin and later with chloramphenicol. Orally administered trimethoprim-sulfamethoxazole, however, resulted in sterilization of the patient's blood and aortic valve which was resected 27 days after the start of therapy. A 6-week course of therapy was completed and, to date (6 months after treatment), there has been no recurrence.

Streptomyces lipmanii produces two β-lactam antibiotics, penicillin N and 7-(5-amino-5-carboxyvaleramido)-7-methoxycephalosporanic acid. Both antibiotics contain α-aminoadipic acid side chains. In similar antibiotics produced by certain fungi, the α-aminoadipoyl moiety is derived from an intermediate in lysine biosynthesis. Our findings indicate, however, that in S. lipmanii, lysine is synthesized via α, ε-diaminopimelic acid—an entirely different biosynthetic route. This finding suggests not only a unique mechanism for the derivation of α-aminoadipate, but also that the system may be particularly amenable to genetic manipulation.

Serum and biliary tract levels of gentamicin were determined in a large series of patients. In only 17.7% of subjects were therapeutic serum levels achieved, even though recommended doses of gentamicin were administered. Therapeutic bile gentamicin levels were reached in only some of the patients with therapeutic serum levels.

Nalidixic acid (nal) susceptibility of clinical isolates of Serratia marcescens from urinary tract infections, wounds, and blood was determined by the standard disk method, and results were compared with results obtained by a standardized tube dilution procedure using five different broth media. An attempt was made to approximate in vivo conditions by using urine as a test medium and correlating the activity of nal in urine with its activity in nutrient, Trypticase soy, brain-heart infusion, and Mueller-Hinton broths. The isolates were consistently susceptible to lower concentrations of nal in nutrient broth than in the other media. The results showed that Mueller-Hinton broth most closely reflected nal activity in urine. A standardized procedure for nal susceptibility testing of urinary tract isolates of S. marcescens is proposed.