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Coccidioidomycosis (CM) is a fungal infection endemic in the southwestern United States (US). In California, CM incidence increased more than 213% (from 6.0/100,000 (2014) to 18.8/100,000 (2017)) and continues to increase as rates in the first half of 2018 are double that of 2017 during the same period. This cost-of-illness study provides essential information to be used in health planning and funding as CM infections continue to surge. We used a “bottom-up” approach to determine lifetime costs of 2017 reported incident CM cases in California. We defined CM natural history and used a societal approach to determine direct and discounted indirect costs using literature, national datasets, and expert interviews. The total lifetime cost burden of CM cases reported in 2017 in California is just under $700 million US dollars, with $429 million in direct costs and $271 million in indirect costs. Per person direct costs were highest for disseminated disease ($1,023,730), while per person direct costs were lowest for uncomplicated CM pneumonia ($22,039). Cost burden varied by county. This is the first study to estimate total costs of CM, demonstrating its huge cost burden for California.

The pharmacokinetics of metronidazole, a drug effective in vitro against most anaerobic bacteria and promising in treating anaerobic infections, are described. Serum and urine levels after single and multiple doses in 10 adult male volunteers were measured by an agar well diffusion bioassay using clostridial species as the test organisms under anaerobic conditions. Peak serum levels averaged 11.5 ,ug/ml and 6.2 ug/ml after single 500-mg and 250-mg doses, respectively. Renal clearance was only 10.2 ml/min per 1.73 M2, and less than 20% of the administered dose was recovered in the urine as active drug in 24 h. The average serum half-life was 8.7 h, and there was no protein binding as determined by an ultrafiltration method. With multiple doses of metronidazole (500 mg four times a day and 250 mg three times a day), blood levels increased progressively for the first few doses and then leveled off, with no significant accumulation occurring between 3 and 7 days. On 250 mg three times a day, serum levels just before the 8 a.m. dose (12 h after the preceding dose) on the third day averaged 3.9 Mg/ml, and before the 8 p.m. dose, 5.7 Mg/ml. For the higher, 500-mg dose (four times a day) regimen, the corresponding minimum serum levels were 13.1 Mig/ml at 8 a.m. and 21.3 Mg/ml at 8 p.m. Peak levels would have been about 10 ,g/ml higher, and since the minimum inhibitory concentrations of most anaerobes including Bacteroides fragilis are less than 6 Mg/ ml, these concentrations should be highly effective therapeutically, even for severe infections.With the increasing awareness of the pathogenicity of anaerobic bacteria, antimicrobial agents which were effective against these organisms are receiving greater attention. Metronidazole [1-(,-hydroxyethyl)-2-methyl-5-nitroimidazole], which has been used effectively for many years against certain protozoal infec-

During and after a 4-hr intravenous infusion of amikacin and kanamycin in a cross-over study in healthy adult male volunteers, average concentrations of drug in serum were similar, with half-lives of approximately 2 hr. Apparent volumes of distribution at the steady state averaged 30% of body weight, and the rate of renal clearance was less than the rate of creatinine clearance (83 vs. 120 ml/min), a finding that indicates tubular reabsorption. The rate of serum clearance was greater than the rate of renal clearance (100 vs 83 ml/min). Urinary excretion in 24 hr averaged 94% of the dose, and there was no binding of serum proteins. In another cross-over study, volunteers received single intramuscular injections of these antibiotics. Peak concentrations of drug in serum after 45 min to 2 hr averaged 19.9 and 19.0 mug/ml for amikacin and kanamycin, respectively. Serum half-lives between 4 and 8 hr after administration of drug were 2 hr, and an average of 94% of the dose was recovered in the urine in 24 hr. Thus, the pharmacologic properties of amikacin and kanamycin were virtually identical.

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