Ampicillin-sensitive Strains Research Articles

Characterization of clinical isolates of Haemophilus influenzae type b for heterogeneous populations of susceptibility to ampicillin.

In this study 80 clinical isolates of Haemophilus influenzae type b from 60 patients were used to analyze if heterogeneous populations of ampicillin resistant and sensitive cells were simultaneously present within each strain and to determine how common this phenomenon was among clinical isolates. A total of 50 ampicillin sensitive clinical isolates were screened for resistance to this antibiotic. It was observed that 32 ampicillin sensitive strains did not contain resistant subpopulations. Furthermore, even with the inducement of resistant subgroups to proliferate under antibiotic-mediated selection using maximum subinhibitory concentrations of ampicillin, no subpopulations of resistant cells were discovered among 18 additional strains. In order to determine whether ampicillin resistance was stable in beta-lactamase-producing H. influenzae clinical isolates, 20 strains from 16 patients were examined. No tendency to segregate into a heterogeneous population of sensitive and resistant clones was found. Furthermore, ampicillin resistance was still uniformly expressed after the treatment of ten strains with the curing agent acridine orange. These results suggest that after extensive evaluation no heterogeneous populations existed with ampicillin resistant and sensitive H. influenzae clinical isolates, indicating that this phenomenon is not a prevalent one.

Ampicillin inactivation in the caecum of axenic, gnotoxenic and conventional lambs: interaction with resistant or sensitive Escherichia coli.

The fate of orally administered ampicillin was studied in axenic lambs, in gnotoxenic lambs given a complex microflora and a mixture of ampicillin resistant and/or sensitive strains of Escherichia coli, and in conventional lambs. In axenic lambs or animals with a sensitive microflora, antibiotic concentrations of 500-1600 micrograms ml-1 were detected in the intestine, and most of the ampicillin passed through the small intestine and entered the large intestine, within 12-15 h of administration. These antibiotic concentrations were sufficient to decrease the numbers of ampicillin-sensitive E. coli from 10(8)-10(9) bacteria ml-1 to about 10(5)-10(6) bacteria ml-1 by 8 h after ampicillin administration. Second and third doses of antibiotic had no further effect on the bacterial count. Administration of ampicillin to animals hosting ampicillin-resistant E. coli resulted in a significant inactivation of the antibiotic in the intestine. As might be expected there was little reduction in the numbers of these organisms. These results are similar to those observed in conventional lambs hosting resistant E. coli as the dominant colibacillary flora.

In vitro activity of temocillin, moxalactam and cefotaxime against gram negative bacteria sensitive or resistant to ureidopenicillins and/or cefacedone

Minimal inhibitory concentrations (MIC's) of temocillin, cefotaxime and moxalactam were determined by agar dilution technique for 225 strains belonging to various species of Enterobacteriaceae and for 58 strains of H. influenzae and H. parainfluenzae. For Enterobacteriaceae, the MIC's of temocillin are distinctly higher than that of cefotaxime and moxalactam. But temocillin activity was not affected by resistance against ureidopenicillins and/or cefacedone. No resistant strains were encountered among E. coli, K. pneumoniae, Proteus spp. except one strain of P. vulgaris. In E. cloacae- strains with resistance against cefotaxime, temocillin was more active than moxalactam. S. marcescens- strains with a high MIC of temocillin were sensitive to cefotaxime and moxalactam. Temocillin is of the same order of activity as ampicillin against ampicillin-sensitive strains of H. influenzae and H. parainfluenzae. Its MIC is not influenced by beta-lactamases of these species.

Potential significance of colonization with beta-lactamase-producing Haemophilus parainfluenzae in children.

Recent surveys in Vancouver showed most healthy children were colonized with beta-lactamase-producing Haemophilus parainfluenzae. Such organisms might alter the effects of penicillins on throat bacteria by local inactivation. To test this hypothesis in vitro, three isolates of beta-lactamase-producing Haemophilus parainfluenzae were each mixed on a membrane with ampicillin-sensitive strains of Haemophilus influenzae type b or group A Streptococcus pyogenes and exposed to ampicillin. When tested alone, susceptible strains were rapidly killed but when tested together with a beta-lactamase producer, they were protected, indicating efficient ampicillin degradation by Haemophilus parainfluenzae strains. If similar interactions occur in vivo, the effects of beta-lactams on throat bacteria could be significantly altered in the presence of beta-lactamase-producing Haemophilus parainfluenzae.

Detection of beta-lactamase in Haemophilus influenzae by immunofluorescence.

Beta-lactamase immunizing antigen was prepared from cells of an ampicillin-resistant strain of Haemophilus influenzae by cold osmotic shock followed by DEAE column fractionation. Nonspecific antibodies were removed by cross-absorption with cells of an ampicillin-sensitive strain of H. influenzae. An residual nonspecific antibodies remaining after cross-absorption were effectively eliminated by dilution of the anti-beta-lactamase serum 1:50. Twenty strains were tested for presence of beta-lactamase by the indirect fluorescent antibody technique. By this technique 91% of the strains in multiple smears were correctly identified as to the presence or absence of beta-lactamase in a blind study. The beta-lactamases of other gram-negative bacteria were not detectable by this technique.

In vitro activity of cefaclor against haemophilus influenzae in comparison to cephalexin, cephradine, cefadroxil, cefatrizine and ampicillin

The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of cefaclor were compared with those of cephalexin, cephradine, cefadroxil, cefatrizine, and ampicillin for 50 strains ofHaemophilus influenzae. The activity of cefaclor and cefatrizine was 8–16 times higher than that of the other cephalosporins and 1/8 that of ampicillin. Cross-resistance between ampicillin and the cephalosporins tested was observed for one strain which did not produce beta-lactamase. No cross-resistance was found for beta-lactamase-producing strains. The killing kinetics of 4 mg/l cefaclor did not differ in two ampicillin-sensitive strains and one beta-lactamase-producing strain which was slightly resistant to ampicillin. The survival rate varied from 10% to 1% after six to seven hours.

In-vitro activity of the novel oxa-beta-lactam antibiotic moxalactam (LY 127935) against dense populations of selected Gram-negative bacilli.

The activity of moxalactam, a new beta-lactam antibiotic with a novel molecular structure, was examined against dense populations of a variety of Gram-negative bacilli. The lytic activity of moxalactam against ampicillin-sensitive strains was similar to ampicillin, but the activity was maintained against ampicillin-resistant strains, including Pseudomonas aeruginosa, irrespective of whether the ampicillin resistance was 'intrinsic' (non-enzymic) or due to beta-lactamase. Of the 18 strains tested only one, a Hafnia sp., failed to respond to moxalactam.

A dose response study with bacampicillin in uncomplicated gonorrhoea

In a systematic study of dose-response relationship 883 patients with uncomplicated gonorrhoea were given single oral doses of 400, 800 or 1600 mg bacampicillin, with 1 g probenecid. A single dose of bacampicillin 800 mg plus probenecid was the minimum effective dose in patients with fully ampicillin-sensitive strains. In patients with gonococci showing reduced sensitivity to ampicillin, 1600 mg bacampicillin was required to reach a cure rate above 95%. Bacampicillin was well tolerated in all treatment groups. Side-effects were reported in 4.6% of the courses of treatment. The most frequent adverse reaction was loose stools (1.9%), which was noted more often after the 1600 mg dose but was considered to be of no or very little clinical importance.

Antibacterial synergism between beta-lactam antibiotics: Results using clavulanic acid (BRL. 14151) with amoxycillin, carbenicillin or cephaloridine

Bacterial resistance to β-lactam antibiotics is becoming increasingly important. This resistance is often mediated by the production of β-lactamase enzymes which destroy the antibiotics. Such resistance might be overcome firstly by developing antibiotics which are resistant to destruction by β-lactamase; secondly, by developing antibiotics of very high potency; thirdly, antibiotics could be developed which release antibacterially active moities on hydrolysis by β-lactamase. The fourth and perhaps one of the most promising approaches is to develop molecules which inactivate β-lactamases. Combinations of broadspectrum penicillins with isoxazole penicillins have been investigated but for various reasons were not successful in therapy. Recently clavulanic acid, a naturally occurring β-lactam molecule, has been investigated by the authors and other workers. Unlike isoxazole penicillins, clavulanic acid inhibits β-lactamase activity at low concentrations. The activity of ampicillin, cephaloridine or carbenicillin in combination with clavulanic acid against 215 bacterial isolates has been investigated. Concentrations as low as 1 mg/l of clavulanic acid regularly rendered ampicillin-resistant strains ofBacteroides fragilis, Haemophilus influenzae andStaphylococcus aureus sensitive to attainable blood concentrations of amoxycillin. 5 mg/l of clavulanic acid brought the majority of strains ofProteus mirabilis, all strains ofProteus vulgaris, most strains ofKlebsiella pneumoniae and a small proportion of ampicillin-resistant strains ofEscherichia coli into the therapeutic range of amoxycillin. Increasing the concentration of clavulanic acid to 10 mg/l rendered the majority of strains ofE. coli sensitive to amoxycillin. The combination did not show enhanced activity againstEnterobacter species,Serratia marcescens, and most strains ofProteus rettgeri andProteus morganii. There was no enhanced activity between carbenicillin and clavulanic acid against either carbenicillin-sensitive or carbenicillin-resistant strains ofPseudomonas aeruginosa. As would be expected the activity of amoxycillin was not enhanced against ampicillin-sensitive strains of various species or against inherently sensitive species. In a single, simple preliminary experimental mouse infection using intra-peritoneal inoculation ofKlebsiella pneumoniae, protection was suggested by a combination of amoxycillin with clavulanic acid given as two doses where as the individual drugs did not protect. It was concluded that the combined use of clavulanic acid with a broad-spectrum β-lactum antibiotic showed therapeutic potential and was deserving of further evaluation.

Occurrence and Transfer of Ampicillin Resistance Associated with Ampicillin-Resistant Haemophilus Influenzae Isolated from a Case at a Day-Care Centre

A 1-year-old boy with recurrent otitis media had been repeatedly treated with antibiotics. A few days after withdrawal of administered ampicillin he again contracted otitis media and ampicillin-resistant Haemophilus influenzae was isolated. The strain was serologically untypable. No ampicillin-resistant H. influenzae was found in his family or at the day-care centre that he attended. The ability to produce the beta-lactamase elaborated from this strain could be transferred to ampicillin-sensitive strains of H. influenzae and Escherichia coli in frequencies of 0.7 X 10(-7) and 4.1 X 10(-4) respectively. The transcipients obtained were ampicillin-resistant and beta-lactamase producing. In the transcipients of E. coli, however, the marker for ampicillin resistance was quite unstable.

CLINICAL, BACTERIOLOGICAL, AND IMMUNOLOGICAL CHARACTERISATION OF AMPICILLIN-RESISTANT HÆMOPHILUS INFLUENZÆ TYPE B

Ampicillin-resistant Hæmophilus influenzæ type b (H.I.T.B.) was isolated from the cerebrospinal fluid of 1 of 3 children with H.I.T.B. meningitis, attending the same day-care centre. 81 children and 13 adults, from the same area as the 3 cases, were examined for nasopharyngeal carriage of H.I.T.B. Six ampicillin-resistant and four ampicillin-sensitive strains were recovered from the children. When 46 of these children were re-examined and had blood drawn one month later, 11 carriers of H.I.T.B. were found. High levels of H.I.T.B. antibody were associated with persistent carriage of either the ampicillin resistant or sensitive strains. All isolates from children at the day-care centre were ampicillin resistant during both surveys.

Activity of FL 1060, a new -lactam antibiotic, against urinary tract pathogens

The effect of the new beta-lactam antibiotic FL 1060 on urinary tract pathogens, of which 71 were sensitive to and 100 resistant to ampicillin, is presented here. When tested by conventional methods FL 1060 was found to be highly active against ampicillin-sensitive strains of E. coli but phenotypically resistant variants readily emerged, particularly when a large inoculum was used. Thirty-one per cent of ampicillin-resistant strains were found to be sensitive to less than 500 mug FL 1060 per ml, and in general this antibiotic was more active than ampicillin against resistant strains. In a system simulating the mechanical features of the urinary bladder the activity of FL 1060 against three sensitive strains of E. coli was found to be greater than ampicillin in conditions of low, but not high, osmolality.

Ampicillin inactivation and sensitivity of coliform bacilli.

SUMMARY: Ampicillin sensitivity tests and tests for ampicillin inactivation were made with 148 strains of coliform bacilli. A correlation was found in strains of Proteus mirabilis and Klebsiella between ampicillin resistance and inactivation. No correlation was obtained with Escherichia coli, whether sensitive or resistant to ampicillin, although small amounts of penicillinase were produced. Ampicillin-sensitive strains of P. mirabilis showed even lower amounts of penicillinase. The strains of Pseudomonas pyocyanea (aeruginosa) were resistant to ampicillin, but also showed low penicillinase levels. No evidence of induction of penicillinase was obtained with E. coli or Klebsiella in the presence of methicillin, ampicillin or cephalosporin C. The ampicillin-inactivating enzyme is a β-lactamase, not an amidase. Resistance of ampicillin-sensitive strains of E. coli was increased rapidly by serial subcultures but was not associated with higher penicillinase values. Ampicillin was inactivated less rapidly than was benzylpenicillin by penicillinase from an E. coli strain.