Limited efficacy of antimicrobial metaphylaxis in finishing pigs: A randomized clinical trial.

Pigs that die from pathogens associated with porcine respiratory disease complex (PRDC) in the late finishing period represent a significant economic wastage. While it is common to apply antimicrobial metaphylaxis (AM) to control PRDC, there are few studies exploring the potential cost-saving benefits of AM. In this study we examined the value of using AM in commercially reared, late finishing pigs, from farms with endemic PRDC. A total of 732 pigs from four AIAO wean to market sources, were blocked into 2 matching cohorts, based on enrollment body weight, sex, and rectal temperature. The cohorts received either control (C) or AM (Tulathromycin 2.5mg/kg IM, Zoetis, Florham Park, NJ, USA). Post treatment weight gain over the 21 day period was used as a measure of health and productivity. The AM treated pigs in the lowest weight quartile at enrollment, showed a significantly improved weight gain over controls (18.5 kg vs. 16.4 kg, mean difference=2.1 kg, CI 1.10-3.10, p=0.005) that was not evident in any other starting weight quartiles. These results indicate that the biological advantage and associated improvement in growth efficiency associated with the use of AM against PRDC, is only conferred to a specific sub-set of animals. The economic advantage of this strategy is therefore, only likely if the indicators of potential benefit (e.g., lighter weight cohort) can be reliably established. Further studies are needed to determine whether targeted AM could be effectively applied across the industry.

In vitro antibacterial activity of fluorinated analogs of chloramphenicol and thiamphenicol.

We evaluated the in vitro antimicrobial activity of Sch 24893, Sch 25298, and Sch 25393, three novel analogs of chloramphenicol and thiamphenicol. All of the analogs had minimal inhibitory concentrations of less than or equal to 10 micrograms/ml for 18 chloramphenicol-thiamphenicol-resistant strains of Shigella dysenteriae and 21 strains of resistant Salmonella typhi. The analogs were also more active than were chloramphenicol and thiamphenicol against chloramphenicol-resistant enteric bacteria, including six strains of Escherichia coli, seven strains of Klebsiella pneumoniae, and two strains of Enterobacter cloacae. Fifty-three strains of ampicillin-resistant Haemophilus influenzae were uniformly susceptible to chloramphenicol, thiamphenicol, and the three analogs. Sch 25298 was the most active compound tested (minimal inhibitory concentration, 0.5 microgram/ml for all strains). Four of seven chloramphenicol-thiamphenicol-resistant Haemophilus strains were susceptible to the fluorinated analogs. Of the three Haemophilus strains which were resistant to chloramphenicol, thiamphenicol, and the analogs, two contained less than 10% of the chloramphenicol acetyltransferase activity of the strains which were resistant to only chloramphenicol and thiamphenicol. We conclude that fluorinated analogs of chloramphenicol and thiamphenicol have considerable in vitro activity against a broad spectrum of chloramphenicol-thiamphenicol-resistant, gram-negative bacteria.

Phenotypic and genetic variation in the susceptibility of Haemophilus influenzae type b to antibodies to somatic antigens.

Haemophilus influenzae type b (H.i.b) has been investigated with respect to phenotypic and genetic variations resulting in differential susceptibility to bactericidal antibody. Previous studies had shown that after growth in infected rats or in dialysate of rat serum, H.i.b strain Eag became more resistant to the bactericidal activity of antisomatic antibody. We now report that a similar phenotypic shift occurs when strain Eag is incubated with dialysate of human serum, that the increased resistance is to antibodies against determinants in the lipopolysaccharide not for the somatic antigens generally, and that most strains of H.i.b undergo the shift. To assess genetic differences in exposed antigens, a panel of 13 H.i.b isolates from cerebrospinal fluid were analyzed with cross-adsorbed antisera. Seven different patterns were found that could be accounted for through the variable expression of six antigens. These ranged from infrequent (found on 1:13 strains) to common (10:13 strains). At least four were somatic rather than capsular determinants; the most common (antigen 1) was contained in lipopolysaccharide. The epidemiologic relevance of the genetic variations was explored using pairs of isolates from two children who had had two documented infections with H.i.b. In both cases the isolates varied in somatic antigen expression. The strains from one patient differed in the expression of antigen 1. The isolates from the other were indistinguishable in sub-typing for the six classified antigens, but differed in the expression of an additional antigen identified by use of the patient's serum.

Evaluation of a rapid beta-lactamase test for detecting ampicillin-resistant strains of Hemophilus influenzae type b.

Chloramphenicol is presently the drug of choice in the initial treatment of serious infections due to Hemophilus influenzae type b. Rapid detection of ampicillin resistance in clinical isolates would facilitate early discontinuation of chloramphenicol therapy in patients infected with ampicillin-sensitive bacteria. A total of 160 strains of H. influenzae type b were tested with a one-hour acidimetric microassay for beta-lactamase activity. All ampicillin-resistant strains rapidly hydrolysed the beta-lactam ring of penicillin. When isolates were encoded and tested without knowledge of their MICs, the 40 ampicillin-resistant strains (MIC greater than or equal to 2 mug/ml) were readily distinguished from 120 sensitive strains. Rapid beta-lactamase assay is therefore a reliable detector of ampicillin resistance in H. influenzae type b.

Hemophilus influenzae type B susceptibility to 17 antibiotics.

One hundred and one strains of Hemophilus influenzae type b isolated at the Children's Hospital Medical Center from blood or CSF and 18 strains known to be resistant to ampicillin of which 17 were supplied to us by others were tested for their sensitivity to 17 antibiotics. Two groups were defined according to their sensitivity to ampicillin. When 10-3 bacteria were applied, 18 strains isolated from patients with ampicillin treatment failures had a median minimum inhibitory concentrations of 3.1 mug/ml. At 10-6 bacteria the median MIC for the resistant strains increased 512-fold, whereas the sensitive strains increased two-fold. The most active antibiotics against sensitive and resistant strains were rifampin, chloramphenicol, gentamicin, rosamycin, and erythromycin with MICs ranging from 0.2-0.8 mug/ml at 10-3 bacteria and from 0.2-1.6 mug/ml at 10-6.

R-factor transfer in selenite and tetrathionate broths.

After overnight incubation of R(+)Escherichia coli with R(-)Salmonella typhimurium in selenite and tetrathionate with Brilliant Green (TBG) broths, R-factor transfer was demonstrated in 10 of 12 experiments. R-factor transfer in these enrichment broths occurred at a markedly reduced frequency in comparison to that in Trypticase soy broth, apparently due to an adverse effect either on the viability of the donor E. coli or the conjugation process itself. Transfer of R factors in commonly used enrichment broths may give rise to falsely resistant antibiotic patterns in Salmonella. However, the frequency of R-factor transfer is so low that it is unlikely to affect significantly the interpretation of R-factor studies.