Biomedical subjects
Publications and source records attributed to W C Anthony.
Primary hepatic actinomycosis is seldom seen, and almost all cases have been diagnosed by laparotomy. Treatment with high-dose parental penicillin for prolonged periods is recommended. In the past concomitant surgical drainage also has been recommended, but the nonoperative success reported here and by others suggests that surgical drainage is not essential to the treatment.
Cefuroxime axetil was compared with cefaclor for the therapy for lower respiratory tract infections. Sixty-one patients were randomized to receive the following drug dosages: (1) cefuroxime axetil, 250 mg orally every 12 hours (21 patients); (2) cefuroxime axetil, 500 mg orally every 12 hours (21 patients); and (3) cefaclor, 500 mg orally every eight hours (19 patients). Of these 61 patients, 80% were male, with a mean age of 59.5 years; 56% had acute pneumonia, and the remainder had an acute bronchitis. Causative pathogens included typical respiratory tract pathogens. Overall, 23 of 27 patients with bronchitis were clinically cured at the end of therapy. Thirty-one of 34 pneumonias were clinically cured or improved at the end of therapy; the three pneumonia treatment failures occurred in the lower dose cefuroxime (n = 2) and cefaclor (n = 1) treatment groups. Overall, bacteriologic cure occurred in 86% of patients treated with 500 mg of cefuroxime axetil compared with 60% of cefaclor-treated patients. Adverse clinical effects were uncommon. From this study, it was concluded that cefuroxime given every 12 hours is at least as clinically efficacious as cefaclor; it is a new oral cephalosporin with pharmacologic and bacterial spectrum advantages over many older agents.
Ceftazidime is a new antimicrobial agent possessing excellent in vitro activity against most members of the family Enterobacteriaceae and against Pseudomonas aeruginosa. We conducted a double-blind, prospective, multicenter trial to compare ceftazidime with moxalactam in the treatment of serious gram-negative infections. The overall favorable response rates for the two regimens were similar (93 of 106 [88%] and 84 of 97 [86%], respectively). Among these, the response rates of the 56 gram-negative bacteremias and the 23 P. aeruginosa infections were comparable. Both groups had similar incidences of subsequent infections with P. aeruginosa, enterococci, and yeasts. A total of 13% of the patients in the moxalactam group developed a prolonged prothrombin time (P less than 0.01), and three patients demonstrated clinical bleeding. These results suggest that although the overall efficacy of both regimens was similar, treatment with moxalactam resulted in a higher incidence of prolongation of prothrombin time with an attendant risk of bleeding. In nonneutropenic patients, ceftazidime as a single agent is safe and effective in gram-negative bacillary infections.
Catheterized patients not only are subject to risks of bacteriuria but the catheter also may act as reservoirs for nosocomial infections. Antibiotics that are concentrated in the urine, even those to which the organisms are nominally resistant, have been advocated as a means of treatment and infection control. During a randomized study of repetitive 10-day courses of cephalexin in chronically catheterized patients we observed the impact of such treatment upon susceptible, moderately resistant and highly resistant strains of bacteria. Cephalexin diminished the persistence of cephalexin-susceptible strains. However, its effect upon moderately resistant (inhibited by 200 micrograms per ml.) was not different than its effect upon highly resistant (not inhibited by 200 micrograms per ml.) strains. Indeed, the persistence of strains of moderately and highly resistant organisms during cephalexin courses was similar to that of such organisms during comparable periods in patients not receiving cephalexin. The administration of cephalexin to chronically catheterized patients with moderately or highly resistant organisms causing bacteriuria does not clear these organisms from the urine.
Patients with long-term indwelling urethral catheters are subject to acute and long-term complications of bacteriuria. To evaluate the common practice of short-course antibiotic therapy in such patients, we performed a randomized controlled trial of ten-day courses of cephalexin monohydrate repeated whenever a susceptible bacteriuria was present. We observed 17 cephalexin group patients for 545 patient-weeks (160 cephalexin courses) and 18 control group patients for 477 patient-weeks. Throughout the study, the groups were comparable in regard to incidence and prevalence of bacteriuria, number of bacterial strains per weekly urine specimen, incidence of febrile days, and incidence of obstructed catheters. In the cephalexin group, the frequency of fever during periods when antibiotics were being used was similar to that during periods when antibiotics were not being used. More cephalexin-resistant bacteria were isolated from cephalexin group patients. Routine treatment with cephalexin of asymptomatic long-term catheterized patients, even for susceptible organisms, does not seem to be warranted.
Bacteriuria is common in chronically catheterized patients and is associated with both acute and chronic complications. Of 605 consecutive weekly urine specimens from 20 chronically catheterized patients, 98% contained bacteria at high concentrations and 77% were polymicrobial. The mean interval between new episodes of bacteriuria was 1.8 weeks. Most species of bacteria caused five to seven new episodes of bacteriuria per 100 weeks of catheterization. Even though access to the catheter lumen was similar, the duration of bacteriuric episodes varied greatly by species. Of the episodes of bacteriuria caused by nonenterococcal gram-positive cocci, greater than 75% lasted less than one week. Mean durations of episodes of bacteriuria due to Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa were four to six weeks, whereas those due to Providencia stuartii averaged 10 weeks and ranged up to 36 weeks. Thus, the very high prevalence of bacteriuria--virtually 100%--was a result of a high incidence caused by many different species combined with the prolonged residence of some gram-negative bacilli in the catheter and urinary tract.
In a previous study, a seronegative child to whom attenuated A/Alaska/77-ts-1A2 virus was administered (37 degrees C shutoff temperature for plaque formation) shed virus with an altered temperature-sensitive (ts) phenotype (40 degrees C shutoff temperature) (Murphy et al., Ann. N.Y. Acad. Sci. 354:172-182, 1980; Tolpin et al., Virology 112:505-517, 1981). This ts+ virus (FV1319) was evaluated for its level of replication in hamsters and for its virulence for humans. In hamsters, FV1319 ts+ virus replicated to the same level in the nasal turbinates as that of which the A/Alaska/77 wild-type virus replicated, but its replication in the lungs was reduced 40-fold. In contrast, the A/Alaska/77-ts-1A2 reassortant achieved a titer in hamster nasal turbinates that was significantly lower (P less than 0.005) than those achieved by the wild-type and the FV1319 viruses; the A/Alaska/77-ts-1A2 reassortant was not recoverable from the lungs. In seronegative adult volunteers, the pattern of replication of the FV1319 virus was similar to that of the A/Alaska/77 wild-type virus. The illness induced by the FV1319 ts+ virus was also similar to that caused by the wild-type virus. In contrast, the A/Alaska/77-ts-1A2 reassortant was satisfactorily attenuated in adult volunteers. These results suggest that attenuation of the A/Alaska/77-ts-1A2 reassortant virus in humans is a function of the ts phenotype: loss of this phenotype restored virulence. The ability of the A/Alaska/77-ts-1A2 reassortant to lose its ts phenotype and regain virulence during growth in a permissive host limits the usefulness of the ts-1A2 reassortants as vaccine viruses for humans.
The influenza A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) virus was evaluated as a donor of attenuating genes to new variants of influenza A virus. This ca donor virus was mated with the A/Alaska/6/77 (H3N2) wild-type virus, and three A/Alaska/6/77 (H3N2) ca recombinant viruses were produced. The parental origin of the genes in the three ca recombinants had been determined previously (2), and their virulence for adult seronegative volunteers was assessed in the present study to identify the genes present in the ca donor virus that confer attenuation. Each of the recombinants received the hemagglutinin and neuraminidase genes from the A/Alaska/6/77 (H3N2) wild-type parent. One ca recombinant (CR-29) received all six transferable genes from the ca parent and was found to be satisfactorily attenuated in the volunteers. The two other ca recombinants received five of the six transferable genes with a wild-type gene at the M or NS locus. The pattern of infection in humans with these latter two ca recombinants was similar to the CR-29 ca recombinant. These findings demonstrate that inheritance of a gene in ca recombinants at the M or NS locus segregates independently of attenuation and suggest that the M and NS genes present in the ca donor virus are not the major determinants of attenuation conferred by this virus.
Two attenuated influenza A donor viruses, the A/Udorn/72 ts-1A2 and the A/Ann Arbor/6/60 cold-adapted (ca) viruses, are being evaluated for their ability to reproducibly attenuate each new variant of influenza A virus to a specific and desired level by the transfer of one or more attenuating genes. Each of these donor viruses has been able to attenuate influenza A viruses belonging to the H3N2 subtype by the transfer of one or more attenuating genes. To determine whether these two donor viruses could attenuate a wild-type virus that belonged to a different influenza A subtype, ts-1A2 and ca recombinants of a wild-type virus representative of the A/USSR/77 (H1N1) Russian influenza strain were prepared and evaluated in adult doubly seronegative volunteers at several doses. The recombinants derived from both donor viruses were attenuated for the doubly seronegative adults. Less than 5% of infected vaccinees developed a febrile or systemic reaction, whereas five of six recipients of wild-type virus developed such a response. The 50% human infectious dose (HID(50)) for each recombinant was approximately 10(5.0) 50% tissue culture infective doses. The virus shed by the ts-1A2 and ca vaccinees retained the ts or ca phenotype, or both. This occurred despite replication of the recombinant viruses for up to 9 days. No evidence for transmission of the ca or ts-1A2 recombinant virus to controls was observed. A serum hemagglutination inhibition response was detected in less than 50% of the infected vaccinees. However, with the more sensitive enzyme-linked immunosorbent assay, a serological response was detected in 100% of the ca vaccinees given 300 HID(50) and approximately 70% of ca or ts vaccinees who received 10 to 32 HID(50) of virus. These results indicate that the recombinants derived from both donor viruses were satisfactorily attenuated and were stable genetically after replication in doubly seronegative adults although they induced a lower serum hemagglutination inhibition response than that found previously for H3N2 ts and ca recombinants.
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Cefoperazone was compared with the combination of cefamandole and tobramycin in a prospective, randomized study of putative, severe, gram-negative bacillary infections. We attempted to exclude patients with granulocytopenia or infections due to Pseudomonas species. A total of 118 isolates (94 gram-negative bacilli and 24 gram-positive cocci) caused infection in 99 of the 120 patients studied. Cefoperazone (16 micrograms/ml) was active against 93% of the organisms tested; cefamandole (16 micrograms/ml) and/or tobramycin (4 micrograms/ml) was active against 95%. Infection was cured or improved in 77% of cefoperazone-treated patients and 81% of cefamandole-tobramycin-treated patients. Bacteremia was cured or improved in 61% of cefoperazone-treated patients and in 63% of cefamandole-tobramycin-treated patients. Adverse reactions included five cases of probable antibiotic-associated nephrotoxicity in the cefamandole-tobramycin group; there were no such cases in the cefoperazone group. One patient given cefoperazone plus eight other drugs became granulocytopenic, but the condition resolved when all medications were stopped. This analysis suggests that cefoperazone alone may be as effective as cefamandole plus tobramycin in the treatment of severe infections with gram-negative bacilli and is less nephrotoxic. The role of cefoperazone in patients with granulocytopenia or infections due to Pseudomonas aeruginosa was not evaluated.