Faculty Bibliography

Sixteen patients with serious Gram-negative bacillary infections were treated with intravenous ceftazidime, 2 g every 8 h. The majority of patients had bacteraemia or pneumonitis or both. Ten patients were cured and six improved. Seven of ten patients infected with Pseudomonas aeruginosa were cured, and three improved. No adverse reactions occurred. Four strains of Ps. aeruginosa became resistant to ceftazidime in patients who were cured or improved clinically. Ceftazidime is effective as single drug therapy for serious Gram-negative infections, including those due to Ps. aeruginosa

Pneumococcal capsular polysaccharide vaccine was administered to 19 cirrhotic patients and to 25 control subjects. Radioimmunoassay antibody concentration and opsonic titers (OT) were measured in sera and ascites collected before and 3 to 4 weeks after inoculation. The geometric mean antibody concentrations in prevaccination sera from the cirrhotic patients were significantly increased to types 3, 4, 7F, 8, 9N, and 12F antigens, and in postinoculation sera their geometric mean antibody concentration was increased to types 3, 9N, and 12F antigens. OT to Streptococcus pneumoniae type 3 correlated with the radioimmunoassay antibody concentration in postinoculation sera. Of 14 cirrhotic subjects, 3 had OT of greater than or equal to 4 in prevaccination sera, and the highest OT and radioimmunoassay antibody concentration were observed in postinoculation specimens from this group. Antibody and OT against S. pneumoniae type 3 were also observed in ascitic specimens. These data suggest that cirrhotic subjects respond to pneumococcal capsular polysaccharide with antibodies in both serum and ascitic fluid. However, the protective efficacy of this antibody response must be assessed by larger prospective studies

Studies to date have indicated that nutritionally-variant streptococci (NVS) causing bacterial endocarditis are frequently inhibited but not killed by low concentrations of penicillin. We report a patient with endocarditis due to a NVS strain which was killed in vitro by penicillin at a concentration of 0.09 microgram/ml. Despite therapy with intravenous penicillin for four weeks, the infection relapsed and was then cured by combined penicillin-gentamicin in therapy. In vitro studies demonstrated a synergistic effect of these two antibiotics. This experience suggests that combination therapy with penicillin and an aminoglycoside may be required for cure of all cases of nutritionally-variant streptococcal endocarditis regardless of in vitro susceptibility to penicillin

The multiple-dose pharmacokinetics and tolerance of intravenous ceftriaxone were investigated in 44 adults with normal renal function. Doses of 0.5, 1.0, and 2.0 g every 12 h and 2 g every 24 h were administered intravenously at a constant rate over 30 min. Plasma and urine samples were collected after the first (day 1) and last (day 4) dose and assayed for ceftriaxone by high-pressure liquid chromatography. Considering all four doses, mean peak plasma concentrations ranged from 79 to 255 micrograms/ml on day 1 and from 101 to 280 micrograms/ml on day 4. Trough concentrations at 12 h on day 1 were 15 to 45 micrograms/ml and 20 to 59 micrograms/ml on day 4. After a dose regimen of 2 g every 24 h, trough levels were still in the clinically therapeutic range (13 to 15 microgram/ml). The mean beta-phase t1/2 was markedly long (6.3 to 6.9 h) and was independent of dose. The fraction of dose excreted unchanged in the urine (0.33 to 0.44) indicated a substantial nonrenal mechanism of elimination. The plasma clearance ranged between 1,002 and 1,449 ml/h, and renal clearance ranged from 353 to 529 ml/h. The apparent volume of distribution varied from 9.2 to 13.5 liters. The dose-related increases in calculated Vd and Clp could be attributed to concentration-dependent plasma protein binding because of a larger free fraction of drug at higher concentrations. The drug was well tolerated, and no significant clinical or laboratory abnormalities were noted

Five men developed disseminated infection with Mycobacterium avium-intracellulare. These patients all lived in the New York City area and presented with their illnesses between January 1981 and September 1981; four were homosexual and one was an intravenous drug abuser. Four patients died. All five patients had defects in the cell-mediated immune response. The infections were characterized histopathologically by poor or absent granulomatous tissue reaction. Clinical isolates of M. avium-intracellulare from all five patients agglutinated commonly used antimycobacterial drugs. The spectrum of opportunistic infections among populations of homosexuals and drug abusers should be expanded to include disseminated disease due to M. avium-intracellulare.

Eighteen patients with 21 serious infections were treated with ceftriaxone, 1 g intravenously every 12 h, for a mean duration of 8 days. Eighteen gram-negative and two gram-positive organisms were isolated. Sites of infection included blood (three patients), urinary tract (six patients), respiratory tract (seven patients), biliary tract (three patients), ascitic fluid (one patient), and skin (one patient). Serum, bile, and ascitic fluid concentrations of ceftriaxone were in excess of the minimal bactericidal concentration required for the infecting organism in all cases. A bacteriological response was demonstrated in 94% of the infections. A clinical response occurred in four infections from which no pathogens were recovered. In one patient, ceftriaxone failed to eradicate a peritoneal infection due to Bacteroides fragilis. In two patients, superinfection with enterococci developed both during and after therapy. Systemic tolerance to ceftriaxone was excellent

Effective therapy for aerobic gram-negative bacillary meningitis is limited by antibiotic resistance among many pathogens and by poor diffusion of some antibiotics into the subarachnoid space. The host response to suppurative meningitis caused by all encapsulated bacteria is impaired by a deficiency of complement and opsonic activity in infected spinal fluid; consequently, therapy with bactericidal antibiotics is preferred. Chloramphenicol diffuses well into cerebrospinal fluid, but is bacteristatic against enteric gram-negative bacilli. Although aminoglycosides are bactericidal, their use requires daily intralumbar or intraventricular injections. Newer cephalosporin compounds, moxalactam and cefotaxime, are bactericidal at very low concentrations and diffuse well from serum to infected spinal fluid. Clinical trials with moxalactam suggest that it is the most effective regimen for enteric gram-negative bacillary meningitis in adults; Pseudomonas aeruginosa and acinetobacter meningitis are most susceptible to a combination of intravenous ticarcillin and aminoglycoside, plus intrathecal aminoglycoside

Trimethoprim-sulfamethoxazole (240 mg of trimethoprim plus 1,200 mg of sulfamethoxazole) was administered intravenously in a volume of 200 ml to 7 volunteers every 12 hr for 4 days. The mean peak levels of TMP and SMZ in plasma were 3.22 and 100 micrograms/ml, respectively, on day 1 and 5.91 and 178 micrograms/ml, respectively, on day 4, when a steady state was achieved. Tests of in vitro susceptibility indicated that these concentrations are bactericidal for a large proportion of enteric gram-negative bacilli