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Susceptibilities of 540 anaerobic gram-negative bacilli to amoxicillin, amoxicillin-BRL 42715, amoxicillin-clavulanate, temafloxacin, and clindamycin.

Agar dilution MIC testing of amoxicillin, amoxicillin-BRL 42715, amoxicillin-clavulanate, temafloxacin, and clindamycin against 496 beta-lactamase-producing anaerobic gram-negative rods revealed MICs for 90% of the strains tested of 256.0 (amoxicillin), 2.0 (amoxicillin-BRL 42715 and amoxicillin-clavulanate), and 4.0 (temafloxacin and clindamycin) microgram/ml. Amoxicillin, temafloxacin, and clindamycin inhibited all 44 beta-lactamase-negative strains (MICs for 90% of the strains tested, less than or equal to 2.0 micrograms/ml). BRL 42715 will not be developed, but temafloxacin merits clinical evaluation.

Amoxicillin

Amoxicillin in the treatment of asymptomatic bacteriuria in pregnancy: a single dose of 3 g amoxicillin versus a 4-day course of 3 doses 750 mg amoxicillin.

A prospective, randomized, controlled comparative clinical trial was carried out with the aim of investigating the efficacy and tolerance of two different dosage regimens of amoxicillin in the treatment of asymptomatic bacteriuria during pregnancy. Patients in group A received a single dose of 3 g amoxicillin, which was compared to a 4-day course of 3 X 750 mg amoxicillin tablets taken every 8 h (group B). Significant bacteriuria (CFU greater than or equal to 10(5)/ml clean catch midstream urine and CFU greater than or equal to 10(4)/ml urine obtained by bladder catheterization) was diagnosed using the dip-slide method (Uricult). 91 pregnant women with a mean gestational age of 25 weeks (14-38) were randomly allocated to the two treatment groups. 53 patients were assigned to group A and 38 patients to group B. The treatment groups were comparable in terms of age and duration of pregnancy. Urine culture tests were performed 1 and 4 weeks after completion of therapy. The predominant species was Escherichia coli, which was isolated in 60-65% of the cases. Bacteriological cure rates at 1 and 4 weeks, respectively, were 77 and 74% in group A, and 62 and 62% in group B. These differences were statistically not significant. The incidence of side effects was 4% in group A and 13% in group B. The results obtained in the present study suggest that in the treatment of asymptomatic bacteriuria in pregnancy, a single dose of 3 g amoxicillin is as effective and acceptable as a 4-day course. In addition, the single-dose regimen offers the advantage of a reduction in total dose, lower costs and better patient compliance.

Adolescent

Beta-lactamase production and susceptibilities to amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole of 320 non-Bacteroides fragilis Bacteroides isolates and 129 fusobacteria from 28 U.S. centers.

beta-Lactamase production (nitrocefin disk method) and agar dilution susceptibility of amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole were determined for 320 Bacteroides species (not Bacteroides fragilis group) and 129 fusobacteria from 28 U.S. centers. Overall, 64.7% of Bacteroides species and 41.1% of fusobacteria were beta-lactamase positive. Among the Bacteroides species, positivity rates were highest for B. bivius (85.0%), followed by B. splanchnicus (83.3%), B. eggerthii (77.8%), and B. oralis (77.1%); 54.5% of black-pigmented Bacteroides species were beta-lactamase positive. Among the fusobacteria, Fusobacterium mortiferum showed the highest rate of beta-lactamase positivity (76.9%). MICs of amoxicillin (128 micrograms/ml) and ticarcillin (64 micrograms/ml) for 90% of all beta-lactamase-positive strains were reduced to 4 and 2 micrograms/ml, respectively, with the addition of clavulanate. MICs of amoxicillin and ticarcillin for 90% of all beta-lactamase-negative strains were 1 and 4 micrograms/ml, respectively, and greater than or equal to 98.4% of the strains were susceptible to the beta-lactams tested. Of the beta-lactamase-producing strains, 45.9% were susceptible to amoxicillin at less than or equal to 4 micrograms/ml and 93.4% were susceptible to ticarcillin at less than or equal to 64 micrograms/ml; the addition of clavulanate raised the rates to 90.4 and 100%, respectively. All strains were susceptible to cefoxitin, imipenem, and metronidazole. The activity of amoxicillin against 29 beta-lactamase-producing strains (10 Bacteroides species and 19 fusobacteria) was not enhanced by the addition of clavulanate; however, 82.7% of these strains were susceptible to amoxicillin, and all were susceptible to ticarcillin. Although beta-lactamase positivity is on the increase in non-B. fragilis group Bacteroides species and fusobacteria, amoxicillin-clavulanate, ticarcillin, cefoxitin, imipenem, and metronidazole should be suitable for the treatment of infections with these strains. The addition of clavulanate does not appreciably improve the efficacy of ticarcillin against these organisms.

Amoxicillin

Influence of ranitidine, pirenzepine, and aluminum magnesium hydroxide on the bioavailability of various antibiotics, including amoxicillin, cephalexin, doxycycline, and amoxicillin-clavulanic acid.

Two randomized double-blind crossover studies and one randomized crossover study were performed to document possible drug-drug interactions between antacids (aluminum magnesium hydroxide, 10 ml per dose for 10 doses), antimuscarinic drugs (pirenzepine, 50 mg per dose for 4 doses), and H2-blockers (ranitidine, 150 mg per dose for 3 doses) and amoxicillin (1,000 mg), cephalexin (1,000 mg), doxycycline (200 mg), and amoxicillin-clavulanic acid (625 mg). Ten healthy volunteers participated in each study. Concentrations in serum and urine were measured by bioassay, and pharmacokinetic parameters were calculated by the usual open one- or two-compartment models (statistics were determined by the Wilcoxon test). The antacid, pirenzepine, and ranitidine had no influence on the bioavailability of amoxicillin, cephalexin, and amoxicillin-clavulanic acid. Only small differences could be observed in the pharmacokinetic parameters, but they are not of therapeutic importance. However, the antacid caused a significant (P less than 0.01) reduction in the gastrointestinal absorption of doxycycline (area under the concentration-time curve, 38.6 +/- 22.7 mg.h/liter, fasting; 6.0 +/- 3.2 mg.h/liter, with antacid), resulting in subtherapeutic levels of doxycycline.

Adult

Comparative efficacies of ciprofloxacin, amoxicillin, amoxicillin-clavulanic acid, and cefaclor against experimental Streptococcus pneumoniae respiratory infections in mice.

Experimental respiratory infections were established in mice by intranasal inoculation of Streptococcus pneumoniae. Inoculation of 10(7) CFU of either S. pneumoniae 1629 or S. pneumoniae 7 produced a fatal pneumonia in nontreated mice 2 to 3 days after infection. Oral therapy was commenced 1 h after infection and was continued three times a day for 2 days. The doses used in mice produced peak concentrations in serum and lung tissue similar to those measured in humans. Ciprofloxacin failed to eliminate either strain of pneumococcus from mouse lungs at any of the doses tested (40, 80, or 160 mg/kg of body weight) by the end of therapy (33 h). Mice that received ciprofloxacin at 160 mg/kg were clear of S. pneumoniae 7 5 days later, whereas persistence and regrowth of S. pneumoniae 1629 resulted in the death of 20% of animals treated with ciprofloxacin. Therapy with cefaclor (20 mg/kg) produced an effect similar to that of ciprofloxacin. In contrast, amoxicillin (10 and 20 mg/kg) and amoxicillin-clavulanic acid (10/5 and 20/10 mg/kg) were significantly (P less than 0.05) more effective in eliminating both strains of S. pneumoniae from the lungs by the end of therapy and, by 168 h, had prevented mortality in 80 to 100% of treated animals. The efficacy of ciprofloxacin against these experimental pneumococcal respiratory infections was poor, despite good penetration into lung tissue, and is a reflection of the low in vitro activity of the quinolone against S. pneumoniae, one of the most common pathogens in community-acquired pneumonia.

Amoxicillin

[Sensitivity of bacteria inducing urinary infections to 3 drugs (amoxicillin, ampicillin and cephalexin) and clinical efficacy of amoxicillin (author's transl)].

MIC of amoxicillin (AMPC), ampicillin (ABPC) and cephalexin (CEX) against bacteria detected from the patients suffering from urinary infections was determined and the clinical efficacy of AMPC was examined. As the result of determining MIC of AMPC against the detected Escherichia coli, 85.4% showed the value of less than 6.25 mcg/ml. AMPC and ABPC seem to be well correlated with each other regarding MIC, and AMPC showed 1 approximately to 2 stage lower concentration than CEX. In connection to clinical efficacy of AMPC, the oral administration at a daily dose of 750 mg gave the effectiveness rate of 92.5%. Few side effects were caused by administering AMPC and this is an excellent drug for healing acute simple urinary infections.

Acute Disease

[Randomized study of amoxicillin-clavulanic acid versus amoxicillin-metronidazole combinations in pyogenic infections of dental origin].

Thirty patients, without any valve defect, cardiac malformation or previous antibiotic administration and presenting dental infections, have been treated either with amoxycillin-clavulanic acid or amoxycillin and metronidazole. Aerobic and anaerobic bacteria have been isolated. These infections were due to mixed flora. Nearly one half of anaerobes were Peptostreptococcus, S. milleri and S. sanguis being predominant among aerobes. The species identified were those found in the mouth in the absence of infection becoming as opportunistic flora. The percentage of cures was equivalent in the two groups. the association amoxycillin-clavulanic acid seems to be as active as amoxycillin + metronidazole on the microflora isolated from dentogenous pyogenic infections.

Adolescent

[Effect of chemical structure of various penicillins on the stability of beta-lactam group in their molecules. VI. Effects of relative humidity and heat on the stability of amoxicillin trihydrate and amoxicillin sodium in the solid phase].

Dependence of stability of Amoxycillin trihydrate (AMOXY. 3H2O) and Amoxycillin-Natrium (AMOXY-Na) upon relative humidity (RH) and temperature was investigated using the iodometric method for the determination of Amoxycillin. The first order rate constants and activation parameters have been determined at controlled moisture conditions. The straightline relationship lg k = f(RH) at T = const. has been stated, which however is fulfilled by AMOXY-Na only at RH greater than or equal to 50%. The calculated factors of the equation lg k = a + b.1/T + c.RH proved to enable estimation of the stability of the studied antibiotics at any climate conditions. The performed kinetic studies have shown that AMOXY-Na undergoes degradation about 1.5 x 10(3) times faster than AMOXY.3H2O, at RH greater than or equal to 50%.

Amoxicillin

Cefpodoxime proxetil compared with amoxicillin-clavulanate for the treatment of otitis media.

In a multicenter, randomized, investigator-blinded trial, patients were randomly selected to receive either cefpodoxime proxetil or amoxicillin-clavulanate potassium orally for the treatment of acute suppurative otitis media. Patients were seen before, during, and at the end of therapy, and 2 to 3 weeks after completion of therapy. A total of 229 patients, 153 receiving cefpodoxime and 76 receiving amoxicillin-clavulanate were entered into the study; all patients were examined to determine drug safety. A total of 146 patients, 98 in the cefpodoxime group and 48 in the amoxicillin-clavulanate group, completed the study and were examined to determine drug efficacy. End-of-therapy microbiologic eradication rates in assessable patients were 92% for cefpodoxime and 86% for amoxicillin-clavulanate (p = 0.14; 95% confidence interval (CI) on difference: -4.4%, 19.2%). End-of-therapy clinical response rates for assessable patients were as follows: cured, 68% for cefpodoxime and 65% for amoxicillin-clavulanate; improved, 24% for cefpodoxime and 23% for amoxicillin-clavulanate; and failed, 8% for cefpodoxime and 13% for amoxicillin-clavulanate (p = 0.57; 95% CI: -8.4%, 16.5%). Recurrence rates at long-term follow-up were 24% for cefpodoxime-treated patients and 25% for those given amoxicillin-clavulanate. Both drugs were well tolerated; 20.9% of those given cefpodoxime and 31.6% of amoxicillin-clavulanate-treated patients had drug-related adverse medical events (p = 0.102; 95% CI: -23.9%, 2.6%). Gastrointestinal complaints were the most frequently reported drug-related side effect in both groups: 11.8% of cefpodoxime-treated patients and 21.1% of those given amoxicillin-clavulanate (p = 0.076; 95% CI: -20.8%, 2.2%). Drug-related dermatologic side effects (e.g., diaper rash, pruritus, urticaria) were reported in 7.8% of cefpodoxime-treated patients and 14.5% of those who received amoxicillin-clavulanate (p = 0.160; 95% CI: -16.6%, 3.3%). Our findings suggest that clinical efficacy for cefpodoxime administered twice daily is equivalent to that of amoxicillin-clavulanate administered three times a day.

Acute Disease

[Controlled multicentric study comparing cefixime and amoxicillin in the treatment of lower respiratory tract infections in adults].

This multicentre, randomized, double-blind study evaluated the effectiveness and safety of cefixime versus amoxicillin. Patients were admitted if they had lower respiratory tract infection with a bacterial pathogen susceptible to both study drugs. Diagnoses included acute respiratory tract infections with no underlying pulmonary pathology (cefixime 21, amoxicillin 27), acute exacerbation of chronic obstructive lung disease (cefixime 32, amoxicillin 42), superinfection of viral bronchitis or lung cancer, and pleuritis (cefixime 10, amoxicillin 6). Patients were treated for at least 10 days with either cefixime 200 mg b.d. or amoxicillin 1 g b.d. A clinical success rate of 80.7 per cent (50/62) in the cefixime group and 82.2 per cent (60/73) in the amoxicillin group was achieved in infections due to susceptible organisms. In acute infections with no underlying pathology, the clinical success rate was 90.5 per cent with cefixime and 81.5 per cent with amoxicillin. Twenty-three cefixime patients and 20 amoxicillin patients were seen 2 to 6 weeks after treatment: there were 2 and 1 clinical recurrences, respectively. All 3 patients were suffering from chronic obstructive lung disease. The bacteriological eradication rate at the end of treatment in assessable patients was 94.7 per cent (17/18) with cefixime and 80 per cent (16/20) with amoxicillin. Six and 11 new organisms appeared, responsible for 2 superinfections under cefixime and 7 under amoxicillin. Treatment was well tolerated by 96.4 per cent of cefixime patients and 90 per cent of amoxicillin patients. This study confirms the value of cefixime as a new oral antibiotic in the treatment of lower respiratory tract infections in adults.

Adolescent

[Talampicillin hydrochloride: Comparison with amoxicillin and ampicillin in the antibacterial activity and pharmacokinetics (author's transl)].

The antibacterial activities, absorption and excretion of talampicillin hydrochloride were compared with those of amoxicillin and ampicillin. Talampicillin hydrochloride showed a broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria as seen in amoxicillin and ampicillin. The antibacterial activities of talampicillin hydrochloride, amoxicillin and ampicillin were quite similar. In experimental murine infection with Staphylococcus aureus, protective effect of talampicillin hydrochloride was superior to ampicillin. For Escherichia coli infection, protective effect of talampicillin hydrochloride was similar to that of amoxicillin, while ampicillin was less active than both talampicillin hydrochloride and amoxicillin. The absorption and excretion of 250 mg equivalent doses of talampicillin hydrochloride, amoxicillin and ampicillin were compared in nine fasting healthy volunteers after oral administration of these antibiotics in randomized triple crossover study. In order to calculate the pharmacokinetic parameters, plasma levels were analyzed using an one-compartment open model, as well as area under the plasma concentration curve (AUC) and urinary excretion. Maximum plasma levels calculated were 2.8 times higher for talampicillin hydrochloride and 1.45 times higher for amoxicillin than for ampicillin. AUC was greater for talampicillin hydrochloride than for amoxicillin and lowest for ampicillin. Urinary excretion of talampicillin hydrochloride as penicillin determined in biological assay was comparable to that of amoxicillin and 1.55 times higher than that of ampicillin. Penicillins can be metabolized to penicilloic acids in the body. After taking into account the penicilloic acid contents in urine, total excretion in urine was 61% for talampicillin hydrochloride, 67% for amoxicillin and 42% for ampicillin during 6 hours after dosing. The absorption of the drugs was evaluated according to the plasma levels, the area under plasma concentration curve and the percentage of excretion in urine. The results obtained showed that talampicillin hydrochloride was well absorbed from the gastro-intestinal tract.

Adult

Effectiveness of continuous vs. intermittent amoxicillin to prevent episodes of otitis media.

The effectiveness of continuous compared with intermittent amoxicillin prophylaxis administered to subjects with a history of recurrent otitis media enrolled during the winter respiratory infection season was assessed in a prospective single blinded clinical trial. Patients with three or more chart-documented episodes of otitis media (OM) in the preceding 6 months were enrolled and randomly assigned to each treatment group. Patients in the continuous group received amoxicillin twice a day every day for up to 4 months. During the same period patients in the intermittent group received amoxicillin twice a day only when they developed respiratory symptoms of congestion, runny nose or cough. Among the 30 patients receiving continuous amoxicillin who were followed for at least 3 months, 22 (73%) had no OM episodes and 8 (28%) had one OM episode. Among the 25 patients receiving intermittent amoxicillin for at least 3 months, 13 (52%) had no OM episodes, 8 (32%) had 1 episode and 4 (16%) had 2 episodes. Significantly fewer patients had fewer than 2 OM episodes on continuous compared with intermittent amoxicillin (P less than 0.04). The incidence density was 0.46 episode/120 days at risk in the continuous treatment group compared with 1.10 episodes/120 days at risk for intermittent treatment (P less than 0.03). Among patients 12 months or older the incidence density of OM episodes per 120 days was 3.5 times higher in the intermittent amoxicillin group (0.80) compared with the continuous amoxicillin group (0.23) (P = 0.05). The incidence densities of the continuous vs. intermittent therapy groups did not differ significantly for patients younger than 12 months of age. The findings suggest that continuous amoxicillin prophylaxis may be more effective than intermittent treatment in preventing OM episodes in patients 12 months or older with a history of recurrent otitis media.

Amoxicillin

Double-blind randomized study comparing the efficacies and safeties of a short (3-day) course of azithromycin and a 5-day course of amoxicillin in patients with acute exacerbations of chronic bronchitis.

The efficacies and safeties of a three-dose regimen of azithromycin (500 mg once daily for 3 days) and a 15-dose regimen of amoxicillin (500 mg three times daily for 5 days) were compared in a double-blind manner in patients with an acute exacerbation of chronic bronchitis. A total of 92% of patients suffered a type 1 exacerbation. Treatment success, defined as cure or major improvement, was achieved in all patients in the azithromycin group by day 5, compared with 23 (92%) of 25 patients in the amoxicillin group. On day 12, these data were 24 of 25 (96%) in the azithromycin group and 20 of 25 (80%) in the amoxicillin group (results were not significantly different). Several pathogens were isolated (MIC ranges [micrograms per milliliter] in parentheses): Haemophilus influenzae or Haemophilus parainfluenzae was isolated 23 times (azithromycin, less than or equal to 0.06 to 32; amoxicillin, 0.12 to 2); Streptococcus pneumoniae was isolated from 11 patients (azithromcyin, less than or equal to 0.06 greater than 256; amoxicillin, less than or equal to 0.06 to 0.25); Moraxella (Branhamella) catarrhalis was isolated from eight patients (azithromycin, less than or equal to 0.06; amoxicillin, less than or equal to 0.06 to 16); and other members of the family Enterobacteriaceae were isolated from eight patients. One patient treated with azithromycin had Legionella pneumophila pneumonia, and another in that group had a significant rise in titer of antibody against influenza A virus. One patient treated with amoxicillin also had a significant rise in titer of antibody against influenza A virus. Microbiological response rates were comparable. One patient who received azithromycin developed abnormal liver function. Two patients treated with amoxicillin developed abnormal liver functions, one developed exanthema, and one treatment was stopped because of nausea. It is concluded that a three-dose (3-day) regimen of azithromycin is as effective clinically and microbiologically as a 15-dose (5-day) regimen of amoxicillin in the treatment of acute exacerbations of chronic bronchitis.

Aged

Amoxicillin or myringotomy or both for acute otitis media: results of a randomized clinical trial.

A total of 536 infants and children with acute otitis media were randomly assigned to one of six consistent year-long regimens involving the treatment of nonsevere episodes with either amoxicillin or placebo, and severe episodes with either amoxicillin, amoxicillin and myringotomy, or, in children aged 2 years or older, placebo and myringotomy. Nonsevere episodes had more favorable outcomes in subjects assigned to treatment with amoxicillin than with placebo, as measured by the proportions that resulted in initial treatment failure (3.9% vs 7.7%, P = .009) and the proportions in which middle-ear effusion was present at 2 and 6 weeks after onset (46.9% vs 62.5%, P less than .001; and 45.9% vs 51.5%, P = .09, respectively). In subjects whose entry episode was non-severe, those assigned to amoxicillin treatment had less average time with effusion during the succeeding year than those assigned to placebo treatment (36.0% vs 44.4%, P = .004), but recurrence rates of acute otitis media in the two groups were similar. In the 2-year-and-older age group, severe episodes resulted in more initial treatment failures in subjects assigned to receive myringotomy alone than in subjects assigned to receive amoxicillin with, or without, myringotomy (23.5% vs 3.1% vs 4.1%, P = .006). In the study population as a whole, severe episodes in subjects assigned to receive amoxicillin alone, and amoxicillin with myringotomy, had comparable outcomes. It is concluded that children with acute otitis media should routinely be treated with amoxicillin (or an equivalent antimicrobial drug). The data provide no support for the routine use of myringotomy either alone or adjunctively.

Acute Disease

Clinical evaluation of pivmecillinam in intractable urinary-tract infections with complications. A comparative study with amoxicillin by a randomized double-blind technique.

A comparative study was made by the double-blind technique in order to make clear the usefulness of pivmecillinam in the treatment of intractable complicated urinary-tract infections using amoxicillin as a reference drug. Pivmecillinam was given in dosage of 400 mg (potency) per day which was one-fifth the dose of amoxicillin 2,000 mg (potency) per day. In global judgement, pivmecillinam was found superior to amoxicillin. It showed a "significant" superiority over amoxicillin for the treatment of, among others, the urinary-tract infections after prostatectomy, which are intractable diseases. When evaluated by symptoms, pivmecillinam improved bacteriuria "significantly" better than amoxicillin. When seen by causative organisms, the pivmecillinam treatment was "significantly" superior to the amoxicillin treatment against E. coli infections. Pivmecillinam was active against amoxicillin-resistant E. coli. Incidence of adverse reactions was less frequent with pivmecillinam than with amoxicillin. These results indicate that pivmecillinam is a drug of high usefulness for the treatment of intractable complicated urinary-tract infections when evaluated using amoxicillin as a reference drug.

Adult

Cefixime compared with amoxicillin for treatment of acute otitis media.

Cefixime was compared with amoxicillin for treatment of acute otitis media in a randomized trial. Results of tympanocentesis on day 3 to 5 of therapy were used as the major outcome. Total daily doses were 8 mg/kg of cefixime and 40 mg/kg of amoxicillin. One hundred twenty-six patients were randomly assigned to receive treatment; 64 cultures grew pathogens. Pathogens were eradicated from the middle ear after 3 to 5 days of therapy in 27 (79.4%) of 34 children given amoxicillin and 26 (86.7%) of 30 children given cefixime (p = 0.47). When Streptococcus pneumoniae cases were analyzed, bacteriologic cure occurred in 14 (93.3%) of 15 children given amoxicillin and 12 (75%) of 16 given cefixime (p = 0.333). When cases of Haemophilus influenzae infection were analyzed, significantly more cures occurred with cefixime (10/10, 100%) than amoxicillin (8/13, 62%) (p = 0.046). Pathogens associated with failure of amoxicillin therapy were H. influenzae (five cases, two beta-lactamase-positive), S. pneumoniae (one case), and Moraxella catarrhalis (one case, beta-lactamase-positive). The four failures with cefixime therapy were all in patients infected with S. pneumoniae. Rates of rash, diarrhea, and vomiting were the same in both groups and did not necessitate stopping therapy. We conclude the following: (1) Cefixime and amoxicillin were equivalent in overall clinical and bacteriologic efficacy for otitis media. (2) Cefixime was more efficacious than amoxicillin in treating H. influenzae otitis media and should be preferred when H. influenzae is the suspected etiologic agent. (3) Side effects of both drugs were mild and equivalent.

Acute Disease

Detection of opportunistic bacterial pathogens with intrinsic amoxicillin- and cephalosporin-resistance in wild koala faecal microbiomes.

Opportunistic bacterial pathogens frequently associated with human clinical infections, including antimicrobial-resistant strains, are infiltrating the microbiomes of wild animals, where they have the potential to negatively impact wildlife health. Bacterial genes conferring resistance to amoxicillin have previously been reported in koala (Phascolarctos cinereus) faecal DNA. Koalas are facing several key threats, including wildfires, and affected individuals may receive amoxicillin therapy to treat burn wounds. This study aimed to identify the species of amoxicillin-resistant bacteria in koala gut microbiomes and determine if they are opportunistic pathogens. Faecal samples collected from 98 wild-caught koalas were cultured using amoxicillin-supplemented media to isolate amoxicillin-resistant Gram-negative enteric bacteria. Isolates were screened using 16S rRNA PCR and Sanger sequencing to identify opportunistic pathogenic species, which then underwent whole-genome sequencing and antimicrobial susceptibility testing. Intrinsically amoxicillin-resistant opportunistic pathogens were obtained from 9.2% (9/98) of koala faecal samples and comprised Klebsiella oxytoca (6/98, 6.1%), Klebsiella pneumoniae (1/98, 1.0%) and Citrobacter spp. (2/98, 2.0%). Seven of nine amoxicillin-resistant opportunistic pathogens also exhibited cephalosporin resistance. Four K. oxytoca isolates belonged to lineages associated with human clinical infections, which also have the potential to cause disease in koalas, including fatal systemic infections in pouch young. The presence of amoxicillin- and cephalosporin-resistant strains may also increase the risk of gut dysbiosis and opportunistic infections when penicillins or cephalosporins are required to treat bacterial infections in koalas, highlighting the importance of good antimicrobial stewardship. The study findings demonstrate the One Health perspective of microbial pathogens and the intertwined microbial ecology between humans and wildlife.

Animals

Bioavailability of oral penicillins in the horse: a comparison of pivampicillin and amoxicillin.

The pharmacokinetics of ampicillin and amoxicillin following intravenous administration at a dose rate of 15 and 10 mg/kg respectively were studied in four healthy adult horses. Pharmacokinetics of pivampicillin and amoxicillin were studied after oral administration to four healthy adult horses. Pivampicillin, a prodrug of ampicillin, was administered orally to starved and fed horses at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Amoxicillin was administered orally to starved horses only, at a dose rate of 20 mg/kg. Ampicillin and amoxicillin concentrations in plasma, synovial fluid and urine were determined. Mean biological half-life of intravenously administered ampicillin and amoxicillin was 1.72 and 1.43 h respectively, whilst the distribution volume (Vss) appeared to be 0.180 and 0.192 1/kg. Orally administered pivampicillin and amoxicillin were rapidly absorbed. A maximum concentration in plasma of 3.80 micrograms/ml was reached 2 h after administration of pivampicillin to starved horses; in fed horses a maximum concentration of 5.12 micrograms/ml was reached 1 h after administration. After oral administration of amoxicillin a maximum concentration of 2.03 micrograms/ml was reached after 1 h. The (absolute) bioavailability of pivampicillin administered orally was 30.9% in starved horses and 35.9% in fed horses. The bioavailability of amoxicillin administered orally was 5.3% in starved horses.

Administration, Oral