Oral Administration Of Antimicrobials Research Articles

Longitudinal effects of oral administration of antimicrobial drugs on fecal microbiota of horses.

Antimicrobial drug-associated diarrhea (AAD) is the most common adverse effect in horses receiving antimicrobials. Little information on how oral administration of antimicrobials alters intestinal microbiota in horses is available. Investigate changes of the fecal microbiota in response to oral administration of antimicrobials. Twenty healthy horses. Prospective, longitudinal study. Horses were randomly assigned to 4 groups comprising 4 horses each: group 1 (metronidazole); group 2 (erythromycin); group 3 (doxycycline); group 4 (sulfadiazine/trimethoprim, SMZ-TMP); and group 5 (control). Antimicrobials were administered for 5 days. Fecal samples were obtained before (day 0) and at 1, 2, 3, 4, 5, 6, and 30 days of the study period. Fecal microbiota was characterized by high throughput sequencing of the V4 region of the 16S rRNA. Horses remained healthy throughout the study. Richness and diversity in doxycycline, erythromycin, and metronidazole, but not SMZ-TMP groups, was significantly lower (P < .05) at multiple time points after administration of antimicrobials compared with samples from day 0. Main changes in the microbiota were observed during the time of antimicrobial administration (day 2-5; weighted and unweighted UniFrac PERMANOVA P < .05). Administration of erythromycin, doxycycline and, to a lesser extent, metronidazole produced a pronounced alteration in the microbiota compared with day 0 samples by decreasing the abundance of Treponema, Fibrobacter, and Lachnospiraceae and increasing Fusobacterium and Escherichia-Shigella. Oral administration of antimicrobials alters the intestinal microbiota of healthy horses resembling horses with dysbiosis, potentially resulting in intestinal inflammation and predisposition to diarrhea.

Prolonged oral antimicrobial administration prevents doxorubicin-induced loss of active intestinal stem cells

ABSTRACT Acute intestinal mucositis is a common off-target effect of chemotherapy, leading to co-morbidities such as vomiting, diarrhea, sepsis, and death. We previously demonstrated that the presence of enteric bacteria modulates the extent of jejunal epithelial damage induced by doxorubicin (DXR) in mice. Despite conventional thinking of the crypt as a sterile environment, recent evidence suggests that bacterial signaling influences aISC function. In this study, we labeled aISCs using transgenic Lgr5-driven fluorescence or with immunostaining for OLFM4. We examined the effect of DXR in both germ free (GF) mice and mice depleted of microbiota using an established antimicrobial treatment protocol (AMBx). We found differences in DXR-induced loss of aISCs between GF mice and mice treated with AMBx. aISCs were decreased after DXR in GF mice, whereas AMBx mice retained aISC expression after DXR. Neither group of mice exhibited an inflammatory response to DXR, suggesting the difference in aISC retention was not due to differences in local tissue inflammation. Therefore, we suspected that there was a protective microbial signal present in the AMBx mice that was not present in the GF mice. 16S rRNA sequencing of jejunal luminal contents demonstrated that AMBx altered the fecal and jejunal microbiota. In the jejunal contents, AMBx mice had increased abundance of Ureaplasma and Burkholderia. These results suggest pro-survival signaling from microbiota in AMBx-treated mice to the aISCs, and that this signaling maintains aISCs in the face of chemotherapeutic injury. Manipulation of the enteric microbiota presents a therapeutic target for reducing the severity of chemotherapy-associated mucositis.

Current status of antimicrobial stewardship programmes in Korean hospitals: results of a 2018 nationwide survey

Antimicrobial stewardship programmes (ASPs) are suggested as a vital strategy to address antimicrobial resistance. To examine the current status of ASPs in Korean hospitals, to identify problems and challenges for the implementation of proper ASPs, and to provide a reference for developing more effective ASP policies. A questionnaire based on the 'Seven Core Elements of Hospital Antibiotic Stewardship Programs' from the US Centers for Disease Control and Prevention was developed, modified from the previous questionnaire on ASPs in Korea, 2015. ASP-participating physicians such as infectious disease specialists (IDSs), paediatric IDSs, and directors of infection control departments were targeted. Only one ASP-associated physician per hospital participated in the survey. The survey response rate was 88.4% (84/95). The median number of medical personnel participating in ASPs was 3 (interquartile range (IQR): 1-5), most of whom were IDS (median: 2; IQR: 1-2). Only 6.0% (5/84) of hospitals had full-time workers for ASPs. Whereas restrictive measures for designated antimicrobials were widely implemented among Korean hospitals (88.1%, 74/84), the proportion of hospitals with interventions for inappropriate long-term antimicrobial use and a conversion strategy from parenteral to oral antimicrobial administration was only 9.5% (8/84) and 1.2% (1/84), respectively. Lack of time, personnel, and appropriate compensation was perceived as the major barrier to establishing an ASP in Korean hospitals. ASPs in Korean hospitals were primarily carried out by one or two IDSs, and programmes mostly comprised restrictive measures for designated antimicrobials. National-level support to implement appropriate ASPs in Korean hospitals is necessary.

Evaluation of the pharmacokinetic parameters of standard oral antibiotics in a bioequivalence study of generic products.

Pharmacokinetic parameters were summarized in clinical bioequivalence studies in Japan to confirm the validity for the use of parameters obtained from the clinical studies. Pharmacokinetic parameters, including maximum plasma/serum concentrations (Cmax), area under the plasma/serum drug concentration-time curve (AUC), time to achieve Cmax (Tmax), and half life (t1/2), of the standard products (original drugs) after oral administration of antimicrobials, including respiratory quinolones, cephalosporins, macrolides, and penicillin-based antibiotics were investigated by use of interview forms and/or package inserts from the generic products and the relationship among the pharmacokinetic parameters such as Cmax, AUC, Tmax, and t1/2 were estimated. In all the studies, the standard and generic products were administrated orally to healthy fasting subjects. Although there was more than a 1.5-fold difference in the Cmax and AUC0-24 h, but not in the Tmax and t1/2 values for levofloxacin tablets and cefacrol tablets, these parameters for other antibiotics were similar in various studies. The obtained results suggested that the parameters obtained from recent bioequivalence studies would be useful in identifying pharmacokinetic behavior of the original drugs, especially early time release; however, the pharmacokinetic results obtained from the recently conducted bioequivalence studies may be superior to those obtained from studies conducted in the past.

The prevalence and impact of antimicrobial allergies and adverse drug reactions at an Australian tertiary centre.

BackgroundThe prevalence and impact of antimicrobial “allergy” labels and Adverse Drug Reactions (ADRs) on antibiotic usage and antimicrobial stewardship initiatives is ill defined. We sought to examine the rate of antimicrobial “allergy labels” at our tertiary referral centre and impacts on antimicrobial usage and appropriateness.MethodsTwo inpatient antimicrobial prevalence surveys were conducted over a 1-week period in November 2013 and 2014 as part of the prospective National Antimicrobial Prescribing Survey (NAPS). Post survey, patients recorded in the NAPS database were assigned to two groups based upon recorded antimicrobial “allergy label” and ADR: (i) Antimicrobial Allergy/ADR (AA) or (ii) No Antimicrobial Allergy/ADR (NAA). Antimicrobial usage and antimicrobial appropriateness were compared between AA and NAA groups.ResultsFrom 509 identified patients the prevalence of an antimicrobial allergy or ADR was 25 %. The prevalence of “allergy labels”/ADR was 10 % (51/509) for penicillin V/G, 5 % (24/509) cephalosporins, 4 % (22/509) trimethroprim-sulfamethoxazole and 3 % (17/509) aminopenicillins. One thousand and seventy antimicrobials were prescribed during the study periods, the median antimicrobial duration was longer in the AA versus NAA group (6 days vs. 4 days; p = 0.018), and proportion of inappropriate antimicrobial prescribing higher in the AA group compared with NAA (29 %; 35/120 vs. 23 %; 86/367, p = 0.22). Oral antimicrobial administration was higher in the NAA than AA group (60 %; 177/297 vs. 46 %; 356/793, p = 0.0001). The proportion of patients that received a β-lactam was lower in the AA versus NAA group (60 % vs. 79 %, p = 0.0001).ConclusionsIn an Australian tertiary referral centre an antimicrobial “allergy” or ADR label was found to significantly impacted on rate of oral antimicrobial administration, beta-lactam usage, antimicrobial duration and antimicrobial appropriateness.

Perceptions and behaviours of infectious diseases physicians when managing urinary tract infections due to MDR organisms.

The objective of this study was to attain a better understanding of infectious diseases (ID) physicians' experience with MDR organism (MDRO) urinary tract infections (UTIs) by means of a survey on disease perception, diagnostic management and treatment preferences. A nine-question survey was developed and distributed to members of the North American Emerging Infections Network (EIN) in September 2013. Seven hundred and fourteen out of 1461 EIN members responded to the survey (49%). The responses of 603 responders were studied. Most providers perceived an increase in the incidence of MDRO UTIs over the past 3 years (75% of adult ID responders and 63% of paediatric ID responders). One hundred and thirty-four (22%) responders prefer intravenous over oral administration of antimicrobials when both are available, 171 (28%) prefer longer durations of therapy when comparing an MDRO with a susceptible isolate of the same species and 142 (24%) order a repeat urine culture as 'proof of cure' after treating an MDRO UTI. Nevertheless, 530 (88%) responders perceived MDRO UTIs to be of similar severity as non-MDRO UTIs. Fifty-five percent of providers prescribed fosfomycin for MDRO UTI at least once; the most common prescribing pattern (among a wide spectrum of approaches) was a single dose (16%). Future studies on MDRO UTIs should clarify the role of resistance in patient outcomes and the comparative efficacy of different antimicrobials. Of particular interest is fosfomycin, which is unrelated to other antibiotic classes and may take a more prominent role in treating MDRO cystitis.

Effect of Diarrheastat® and Enrosol-S® on rumen ecosystem in rams

The effect of two antimicrobials (Diarrheastat® and Enrosol-S®) on sheep rumen ecosystem (pH, viscosity, microbial activity and protozoal activity) was investigated in adult rams. The rams were randomly divided into two groups; each group included four rams dosaged orally one time daily for three successive days according to the manufacturer recommendations. Ruminal fluid was analyzed before dosage, after 24 hrs of the first, second and third doses, and after 3, 7 and 10 days after the last dose (3rd dose). No significant differences in ruminal fluid pH and viscosity with oral antimicrobial administration were noticed. Microbial activity tests used (methylene blue reduction test and floatation/sedimentation test) showed a significant reduction of microbial activity of rumen (P

Immune-mediated pure red cell aplasia in a domestic ferret

An 8-month-old spayed female domestic ferret (Mustela putorius furo) was referred for examination to determine the cause of lethargy and severe anemia. Initial examination revealed that the ferret was lethargic but with appropriate mentation. The only other abnormal findings were severe pallor of the mucous membranes, nasal planum, and skin and a PCV of 8%. Pure red cell aplasia (PRCA) was diagnosed on the basis of cytologic evaluation of a bone marrow biopsy specimen. Medical treatment included blood transfusions, IM administration of iron dextran, oral administration of antimicrobials and gastrointestinal tract protectants, and SC administration of erythropoietin. Once PRCA was diagnosed, the ferret was orally administered prednisone, cyclosporine, and azathioprine. Nine months after onset of treatment, the PRCA was in remission and the ferret was doing well. Immunosuppressive treatment was discontinued at 14 months after onset of treatment, and 36 months after initial examination, the ferret appeared to be healthy. It is important that PRCA be considered as a differential diagnosis for a ferret with severe anemia. Prolonged immunosuppressive treatment was successful in the ferret described here.

Eradication of the commensal intestinal microflora by oral antimicrobials interferes with the host response to lipopolysaccharide

The host components and commensal microorganisms of the intestinal microenvironment play roles in the development and maintenance of the host defence. Recent observations have suggested that toll-like receptors (TLRs) are involved in the recognition of innate immunity against intestinal microbes. However, little is known regarding the role of TLR in the maintenance of systemic host defence by intestinal microorganisms. We studied the expression and function of TLR4 and TLR2 on alveolar and peritoneal macrophages in mice after 3 weeks of oral administration of streptomycin and cefotaxime. After active treatment, the intestinal microorganisms were nearly completely eradicated, and the surface expression of TLR4 and TLR2 on the peritoneal macrophages was prominently downregulated. When the actively treated mice were challenged with lipopolysaccharide (LPS), a TLR4 ligand, the host response was markedly impaired. Our results suggest that the oral administration of antimicrobials downregulates the expression of surface TLR on the peritoneal macrophages and modulates the host immune responses against LPS by modifying the intestinal environment.

Risk factors for surgical site infection-inflammation in dogs undergoing surgery for rupture of the cranial cruciate ligament: 902 cases (2005–2006)

To evaluate the incidence of and potential risk factors associated with development of postoperative infection-inflammation in a large number of dogs with rupture of the cranial cruciate ligament (CCL) that were treated via elective surgery. Retrospective case series. 808 dogs that underwent surgery (902 procedures) for rupture of the CCL. Medical records of dogs that underwent extracapsular lateral suture (ECLS) stabilization or tibial plateau leveling osteotomy (TPLO) between January 1, 2005, and December 31, 2006, were reviewed. Data regarding development of postoperative infection-inflammation were obtained. Potential risk factors were identified and recorded. 496 ECLS surgeries were performed, and 406 TPLO surgeries were performed. Infection-inflammation developed in 55 of 902 (6.1%) surgeries within 6 months after surgery. There was a significant difference in infection-inflammation rate after the ECLS surgeries (21/496 [4.2%]), compared with rate after the TPLO surgeries (34/406 [8.4%]). Factors associated with a significantly lower rate of infection-inflammation included the use of suture material other than stainless-steel staples for skin closure and postoperative oral administration of antimicrobials. TPLO was associated with a significantly higher rate of infection-inflammation than the infection-inflammation rate after ECLS stabilization. The use of suture material other than staples for skin closure and postoperative oral administration of antimicrobials may be protective in minimizing infection-inflammation in dogs with rupture of the CCL that are treated via ECLS or TPLO.

Efficacy of azithromycin for the treatment of feline chlamydophilosis

The current recommended treatment for feline chlamydophilosis involves daily oral administration of antimicrobials to all cats within an affected group for a prolonged period of time (4–6 weeks). Not surprisingly, owner compliance can be poor resulting in apparent treatment failure. Recent anecdotal evidence, supported by its efficacy in the treatment of Chlamydia trachomatis infection in humans, has suggested that azithromycin may offer an alternative by allowing less frequent dosing for a shorter duration. A clinical trial was designed to evaluate the efficacy of azithromycin for the treatment of chlamydia ( Chlamydophila felis) infection in cats. Whilst azithromycin, given at 10–15 mg/kg daily for 3 days and then twice weekly, provided a similar, rapid resolution of clinical signs and negative isolation scores as doxycycline, C felis was re-isolated in four out of the five cats treated. Furthermore, even daily administration of azithromycin to chronically infected cats was ineffective in clearing infection. The azithromycin protocols used here were therefore found to be unsuccessful in eliminating the carriage of this strain of C felis.

A field study on the effect of the dietary use of a clinoptilolite-rich tuff, alone or in combination with certain antimicrobials, on the health status and performance of weaned, growing and finishing pigs

This study was conducted to assess the effect of dietary use of a clinoptilolite-rich tuff (Cp) on health status and performance of weaned, growing and finishing pigs and its compatibility during simultaneous oral administration of antimicrobials (AM) such as enrofloxacin (E) or salinomycin (S). Weaners (720) were assigned in 2 experimental groups and 4 subgroups based on the inclusion or not of Cp and AM in their feed (subgroups: NC, ES, Cp, Cp + ES) in order to evaluate their health status, under PWDS prevailing herd conditions. A second part of the trial aimed to the evaluation of piglet performance under conditions with minimized PWDS herd risks. For this purpose, a second set of 264 weaners were assigned in 2 groups and 4 subgroups, in a respective manner. All piglets remained on-trial until slaughtering age; Cp was incorporated in their feed at a rate of 2% from the day of weaning until slaughtering. The health status evaluation consisted in monitoring piglets for adverse effects related to Cp consumption, average daily diarrhoea scoring during weaning and mortality rate calculations throughout. Performance evaluation included individual weighing at the end of weaning, growing and fattening periods and feed consumption assessments. Average daily gain (ADG), average daily feed intake (ADFI) and feed conversion ration (FCR) on a pen basis were further calculated. Cp ingestion was well tolerated by the piglets. Simultaneous administration of Cp and AM in feed, resulted in less severe forms of PWDS, which had a shorter clinical course ( P<0.05). Mortality decreased ( P<0.05) during the weaning period due to AM administration. Concerning mean pig body weight at the end of each production phase, both Cp and AM had favorable effects ( P<0.05). ADG estimated for the whole observation period was improved ( P<0.05) by Cp-use along with AM. FCR improvements ( P<0.05) were noticed during the different stages of growth due to AM or Cp administration, while Cp/AM interaction was noticed only at weaning ( P<0.05).

A pharmacist-initiated program of intravenous to oral antibiotic conversion.

A prospective program to convert patients from parenteral to oral antibiotics was evaluated over 12 months to determine its pharmacoeconomic impact on antibiotic acquisition and length of hospital stay. Physicians of patients meeting predetermined clinical criteria for mild and moderate infections were contacted to discuss potential oral alternative therapy. Clinical end points and economic data were followed in 242 patients (200 converted and 42 not converted but meeting criteria). No significant differences were noted between the groups with regard to demographic data, infection diagnosis, clinical outcome, or adverse effects. The average number of days of therapy for patients converted was 1.53 days shorter than that of patients who were not converted to oral therapy (p < 0.003). Cost savings for drug acquisition and length of stay were $15,149.24 and $161,071.88, respectively. The intervention program appeared to provide a cost-effective conversion from parenteral to oral antimicrobial administration without compromising patient care. It is anticipated that expansion of the program to include additional antibiotics will result in even greater cost savings for the institution.

Omental pedicle used to manage a large dorsal wound in a dog

An eight-year-old miniature schnauzer was presented with full thickness skin necrosis over most of the back, probably caused by a chemical burn. Management consisted of debridement, bandaging, hyperbaric oxygen therapy, topical application of tris-EDTA and oral administration of antimicrobials. A pedicle created from the greater omentum was used to fill the wound and provide a vascular bed for a full thickness meshed skin graft. Despite epidermal loss from the majority of the graft, the wound healed with acceptable appearance and function. This is the first clinical case described in the veterinary literature using an omental pedicle in prepare a free skin graft bed.