Hoigné's syndrome, an uncommon mimicker of anaphylaxis: Systematic literature review.

The term Hoigné's syndrome denotes a mimicker of anaphylaxis, which occurs immediately after the parenteral administration of a drug and is likely caused by non-thrombotic pulmonary and systemic drug micro-embolization. It has so far been documented uniquely in case reports and small case series. Because this condition has never been systematically evaluated, we performed a structured literature review (pre-registered as CRD42023392962). The search was carried out in Excerpta Medica, National Library of Medicine, and Google Scholar. Cases with features consistent with anaphylaxis, urticaria, angioedema, asthma, syncope, anxiety, or panic attack triggered by needle phobia, and local anesthetic systemic toxicity were excluded. For the final analysis, we retained reports published between 1951 and 2021, which presented 247 patients with Hoigné's syndrome: 37 children and 211 adults with a male: female ratio of 2.1 : 1.0. The patients presented within 1 min after parenteral administration of a drug (intramuscular penicillin in 90 % of the cases) with chest discomfort, shortness of breath, fear of death, psychomotor agitation, and auditory or visual hallucinations and impairment. Recovery occurred within 30 min. The diagnosis of Hoigné's syndrome was also established in five patients 66-91 years of age with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the aforementioned symptoms. It was therefore speculated that pulmonary drug micro-embolization induced a lethal cardiovascular compromise in these individuals. Histologic investigations supporting this hypothesis were performed in only one case. The diagnosis of Hoigné's pulmonary drug micro-embolization was established also in five patients with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the afore mentioned symptoms. Histologic investigations supporting this hypothesis were performed in only one case. In conclusion, Hoigné's syndrome is an uncommon non-immune-mediated reaction. This report seeks to promote broader awareness and knowledge regarding this alarming mimicker of anaphylaxis. Diagnosis relies solely on clinical evaluation.

Effect of Procaine Penicillin G and Flunixin Meglumine on Serum Amyloid A Response in Healthy Adult Horses.

This study was designed to determine the effect of PPG and/or flunixin meglumine on SAA response when used at clinical dosing regimens in healthy adult horses. Six healthy adult horses were enrolled in a crossover study design including one control and three treatment groups: no treatment (control); PPG alone (intramuscularly q12h for 72h); flunixin meglumine alone (intravenously q24h for 72h); and PPG (intramuscularly q12h for 72h) and flunixin meglumine (intravenously q24h for 72h). Whole blood was collected at 0, 24, 48, 72, 96 and 120 hours post-initial drug administration to measure SAA using a commercial lateral-flow immunoassay. The washout period was 30 days. Individual SAA values were within the reference range (≤ 20 µg/mL) for almost all horses in the control group. One control horse displayed a SAA value of 28 µg/mL at 72 hours. All horses from the PPG group showed normal SAA values throughout the study. Apart from one horse (SAA of 24 µg/mL at 96 hours) from the flunixin meglumine group, all horses showed normal SAA values. For the PPG and flunixin meglumine group, 5 horses had SAA values within reference range. One horse displayed increased SAA values (32-45 µg/mL) between 48 to 96 hours post-drug administration. There was no difference in area under the SAA time curve amongst control and treatment groups (P > 0.05). The administration of intramuscular PPG and/or intravenous flunixin meglumine does not trigger an inflammatory response that induces a SAA value above reference range in most adult healthy horses.

Quantum and experimental investigation of the application of Crassostrea gasar (mangrove oyster) shell-based CaO nanoparticles as adsorbent and photocatalyst for the removal of procaine penicillin from aqueous solution.

The present study was designed to synthesize and characterize calcium oxide nanoparticles (using mangrove oyster shell as a precursor) and apply the synthesized nanoparticles as a photocatalyst to degrade procaine penicillin in an aqueous solution. The photocatalyst exhibited an average band gap of 4.42 eV, showed a maximum wavelength of absorbance in the UV region (i.e., 280 nm), and is a microporous nanoparticle with a particle diameter of 50 nm. The photocatalyzed degradation of the drug was conducted under natural sunlight, and the influence of parameters such as the period of contact, catalyst load, pH, initial drug concentration, and ionic strength was investigated concerning the degradation profile. The results obtained from response surface analysis indicated that an optimum degradation efficiency of about 93% can be obtained at a concentration, pH, and catalyst dosage of 0.125 M, 2, and 0.20 g respectively, at 0.902 desirabilities. The Langmuir-Hinshelwood, modified Freundlich, parabolic diffusion, pseudo-first-/second-order, and zero-, first-, and second-order kinetic parameters were tested to ascertain the best model that best described the experimental data. Consequently, the Langmuir-Hinshelwood, modified Freundlich, and pseudo-second-order models were accepted based on the minimum error and higher R2 values. Based on the Langmuir-Hinshelwood rate constants for adsorption and photodegradation as well as the evaluated valence bond potential, the degradation of the drug first proceeded through the mechanism of adsorption and followed by the oxidation of the drug by superoxide (generated from the interaction of electrons that generated by through the absorption of UV radiation). The quantum chemical calculation gave evidence that pointed towards the establishment of strong agreement with experimental data and also showed that the carboxyl functional group in the drug is the target site for adsorption and subsequent degradation.

Plasma Creatine Kinase and Aspartate Aminotransferase Activities Before, During, and After 5 Days of Intramuscular Penicillin Administration in Sedentary Horses.

Muscle damage can result in leakage of intracellular enzymes such as creatine kinase (CK) and aspartate transaminase (AST) into plasma. There are no controlled documentations of the effects of intramuscular antibiotic drug administration on plasma CK and AST activities in horses. The objective of this experiment was to test the hypothesis that 5 days of intramuscular procaine penicillin G injection in normal horses would result in increased plasma activities of CK and AST. Nine healthy adult horses were sampled for 7 days preceding, 5 days during, and 32 days following procaine penicillin G (22,000 IU/kg) administration intramuscularly twice daily. Heparinized jugular venous blood samples were obtained daily before treatment and were analyzed the same day for plasma activities of CK and AST. Repeated measures ANOVA and post hoc Tukey's Test were used to identify days where CK or AST were elevated compared to control means at a significance level of P < .05. Beginning the day after first injection, plasma CK increased above the reference range, peaking at 2,046 ± 627 U/L after 3 days, and returned to 227 ± 57.3 U/L (within the reference range) 9 days after treatment began. Beginning the day after first injection, plasma AST increased, peaking at 703 ± 135 U/L on the day after the last injection. Plasma AST did not return to the reference range in all individual horses until 29 days after the last injection (mean 247 ± 33 U/L). Compared to the control period, plasma CK and AST elevations lasted for 8 and 28 days, respectively, after the onset of treatment (P < .001 to P = .03) and lasted for 4 and 24 days, respectively, after the last day of treatment (P < .001 to P = .03).

Acute phase protein concentrations following serial procaine penicillin G injections in horses.

BACKGROUND: Acute phase protein (APP) measurement is used to detect inflammation. Intramuscular (IM) injections could cause tissue injury and induce an acute phase response (APR). OBJECTIVES: To evaluate the effects of IM procaine penicillin G (PPG) injections on APP concentrations in horses. STUDY DESIGN: Prospective longitudinal design. METHODS: PPG was administered intramuscularly to six horses, twice daily, for 5 days. Plasma fibrinogen (FIB), serum amyloid A (SAA), haptoglobin (HAP), creatine kinase (CK), and aspartate aminotransferase (AST) were quantified daily for 5 days before the first injection, during the course of administration, and for 4 days after the final dose. Analytes were quantified every other day for the remaining 16 days. Data were compared using a parametric or non-parametric repeated measures ANOVA and a Tukey's or Mann-Whitney rank sum test, respectively. Significance was set at p < 0.05. RESULTS: CK was increased over baseline (mean ± SD: 200 ± 74 IU/L) on Days 1-6 (p < 0.001 to p = 0.02, mean ± SD: 723-1177 ± 355-544 IU/L) and AST was increased above baseline (mean ± SD: 233 ± 58 IU/L) on Days 2-7 and 10 (p < 0.001 to p = 0.05, mean ± SD: 307-437 ± 79-146 IU/L). Increased FIB was noted over baseline (mean ± SD: 177 ± 30 mg/dl) on Days 6-8 and 10 (p = 0.02 to p = 0.03, mean ± SD: 234-252 ± 33-49 mg/dl). SAA was increased above baseline (mean ± SD: 4.7 ± 2.9) on Day 6 (p = 0.02, mean ± SD: 113 ± 186 µg/ml). There was no change in HAP. MAIN LIMITATIONS: Healthy horses were used, small sample size, and a lack of a negative control group. CONCLUSIONS: Serial intramuscular procaine penicillin G (IM PPG) injections may result in increased positive APP concentrations in horses and this must be considered when these test results are interpreted.

Oral amoxicillin plus gentamicin regimens may be superior to the procaine-penicillin plus gentamicin regimens for treatment of young infants with possible serious bacterial infection when referral is not feasible: Pooled analysis from three trials in Africa and Asia.

Background: Hospital referral and admission in many- low and middle-income countries are not feasible for many young infants with sepsis/possible serious bacterial infection (PSBI). The effectiveness of simplified antibiotic regimens when referral to a hospital was not feasible has been shown before. We analysed the pooled data from the previous trials to compare the risk of poor clinical outcome for young infants with PSBI with the two regimens containing injectable procaine penicillin and gentamicin with the oral amoxicillin plus gentamicin regimen currently recommended by the World Health Organization (WHO) when referral is not feasible. Methods: Infant records from three individually randomised trials conducted in Africa and Asia were collated in a standard format. All trials enrolled young infants aged 0-59 days with any sign of PSBI (fever, hypothermia, stopped feeding well, movement only when stimulated, or severe chest indrawing). Eligible young infants whose caretakers refused hospital admission and consented were enrolled and randomised to a trial reference arm (arm A: procaine benzylpenicillin and gentamicin) or two experimental arms (arm B: oral amoxicillin and gentamicin or arm C: procaine benzylpenicillin and gentamicin initially, followed by oral amoxicillin). We compared the rate of poor clinical outcomes by day 15 (deaths till day 15, treatment failure by day 8, and relapse between day 9 and 15) in reference arm A with experimental arms and present risk differences with 95% confidence interval (CI), adjusted for trial. Results: A total of 7617 young infants, randomised to arm A, arm B, or arm C in the three trials, were included in this analysis. Most were 7-59 days old (71%) and predominately males (56%). Slightly over one-fifth of young infants had more than one sign of PSBI at the time of enrolment. Severe chest indrawing (45%), fever (43%), and feeding problems (25%) were the most common signs. Overall, those who received arm B had a lower risk of poor clinical outcome compared to arm A for both per-protocol (risk difference = -2.1%, 95% CI = -3.8%, -0.4%; P = 0.016) and intention-to-treat (risk difference = -1.8%, 95% CI = -3.5%, -0.2%; P = 0.031) analyses. Those who received arm C did not have an increased risk of poor clinical outcome compared to arm A for both per-protocol (risk difference = -1.1%, 95% CI = -2.8%, 0.6%) and intention-to-treat (risk difference = -0.8%, 95% CI = -2.5%, 0.9%) analyses. Overall, those who received arm B had a lower risk of poor clinical outcome compared to the combined arms A and C for both per-protocol (risk difference = -1.6%, 95% CI = -3.5%, -0.1%; P = 0.035) and intention-to-treat (risk difference = -1.4%, 95% CI = -2.8%, -0.1%; P = 0.049) analyses. Conclusions: Analysis of pooled individual patient-level data from three large trials in Africa and Asia showed that the WHO-recommended simplified antibiotic regimen B (oral amoxicillin and injection gentamicin) was superior to regimen A (injection procaine penicillin and injection gentamicin) and combined arms A and C (injection procaine penicillin and injection gentamicin, followed by oral amoxicillin) in terms of poor clinical outcome for the outpatient treatment of young infants with PSBI when inpatient treatment was not feasible. Registration: AFRINEST study [9] is registered with the Australian New Zealand Clinical Trials Registry: ACTRN12610000286044. SATT Bangladesh study [10] is registered with ClinicalTrials.gov: NCT00844337. SATT Pakistan study [11] is registered at ClinicalTrials.gov: NCT01027429.

Clinical Outcome of Transcervical Infusion of a Combination of Procaine Penicillin and Gentamicin in Late-term Pregnant Mares.

Transcervical intrauterine infusion of antibiotics may more effectively treat pathogens associated with fetal and neonatal disease in pregnant mares than standard systemic routes. The objective of this study was to assess the safety of transcervical antibiotic infusion by characterizing the gestational outcome in nine healthy pregnant pony mares following a single transcervical infusion of 2.4 million IU of procaine penicillin and 200 mg of gentamicin in a 10 mL volume during late gestation. Assessment of fetal-placental health was performed through serial measurement of the combined thickness of the uterus and placenta (CTUP) and fetal heart rate and mares and foals were closely monitored in the periparturient period. Fetal heart rate and CTUP remained unchanged after infusion, with no evidence of fluid accumulation or significant increase at the time-points 24, 48, and 72 hours. All mares foaled without complication 12-58 days after antibiotic infusion at a mean gestational age of 322.7 ± 12.7 days. Two out of nine foals displayed signs of mild neonatal maladjustment syndrome that responded to minimal supportive care and all foals survived to weaning without further complications.

Neurosyphilis Treatment Outcomes After Intravenous Penicillin G Versus Intramuscular Procaine Penicillin Plus Oral Probenecid.

BACKGROUND: Data comparing neurosyphilis treatment regimens are limited. METHODS: Participants were enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis that was conducted at the University of Washington between April 2003 to May 2014. They were diagnosed with syphilis and referred by their providers due to concerns for neurosyphilis. We evaluated 150 people with CSF abnormalities who were treated with either intravenous aqueous penicillin G (PenG) or intramuscular aqueous procaine penicillin G plus oral probenecid (APPG-P). An abnormal CSF diagnosis was defined as a white blood cell (WBC) count >20/µL, a CSF protein reading >50 mg/dL, or a reactive CSF-Venereal Disease Research Laboratory test (VDRL). Hazard ratios for normalization of CSF or serum measures were determined using Cox regression. RESULTS: In individuals treated with either PenG or APPG-P, CSF WBCs and CSF-VDRL reactivity normalized within 12 months after treatment, while protein normalized more slowly and less completely. There was no relationship between treatment regimen or human immunodeficiency virus (HIV) status and likelihood of normalization of any measure. Among those living with HIV, CSF WBC counts and CSF-VDRL reactivity were more likely to normalize in those treated with antiretrovirals. Unexpectedly, CSF WBCs were more likely to normalize in those with low CD4+ T cell counts. When neurosyphilis was more stringently defined as a reactive CSF-VDRL, the relationship with the CD4+ T cell count remained unchanged. CONCLUSIONS: In the current antiretroviral treatment era, neurosyphilis treatment outcomes are not different for PenG and APPG-P, regardless of HIV status. The relationship between the normalization of CSF WBC counts and CD4+ T cell counts may indicate continued imprecision in neurosyphilis diagnostic criteria, due to HIV-related CSF pleocytosis.

An atypical Bacillus anthracis infection in a bull-A potential occupational health hazard.

Bacillus anthracis infecting cattle is usually identified based on the typical symptom: sudden death. Bacillus anthracis causing atypical symptoms may remain undiagnosed and represent a potential occupational health hazard for, that is veterinarians and producers, butchers and tanners. In the year 2004, one case of sudden death in a dairy farm in southern Finland was diagnosed as bovine anthrax. Four years later 2008, an atypical case of anthrax was diagnosed in the same holding. The bull was taken to the Production Animal Hospital of the Faculty of Veterinary Medicine, University of Helsinki because of fever, loss of appetite and a symmetrically swollen scrotal sac. Penicillin treatment cured the fever but not the swollen scrotum. Before the intended therapeutic castration, a punctuate consisting of 10 ml fluid collected into a syringe from the scrotal sac was cultivated on blood agar at 37°C. After 24 hr, an almost pure culture of a completely non-hemolytic Bacillus cereus-like bacteria was obtained. The strain was identified as B. anthracis using Ba-specific primers by the Finnish Food Safety Authority (RUOKAVIRASTO). After the diagnosis, the bull was euthanized and destroyed, the personnel were treated with prophylactic antibiotics and the clinic was disinfected. In this particular case, treatment with water, Virkon S and lime seemed to be effective to eliminate endospores and vegetative cells since no relapses of anthrax have occurred in 10 years. This case is the last reported anthrax case in Finland.

Procaine penicillin alters swimming behaviour and physiological parameters of Daphnia magna.

Procaine penicillin (PP) is a ß-lactam antibiotic widely used in human and veterinary medicine. Although PP is detected in surface water, little is known on its effects on aquatic invertebrates. Our aim was to determine the influence of PP on swimming behaviour (track density, swimming speed, turning angle, hopping frequency) and physiological activity (oxygen consumption, heart rate, thoracic limb movement) of a freshwater invertebrate Daphnia magna exposed to PP at concentrations of 11.79 mg/L, 117.9 mg/L and 1179 mg/L for 2 h and 24 h. The results showed no mortality; however, reduction of swimming activity manifested by the decreased track density, swimming speed and turning angle noted in Daphnia exposed to all the concentrations of PP. Increase of oxygen consumption was observed after 2-h exposure; however, decrease of this parameter was found after 24 h. PP also reduced heart rate and thoracic limb movement in a concentration-dependent manner. The results suggest that the antibiotic should not induce mortality; however, it may affect swimming behaviour and physiological parameters of Daphnia magna particularly inhabiting aquaculture facilities with intensive antibiotic treatment. On the basis of the present results, we also suggest higher sensitivity of behavioural and physiological parameters of cladocerans than the commonly used endpoints: mortality or immobilisation and their possible application as a part of early warning systems in monitoring of surface water toxicity.

[New drugs for small animals in 2018]. / Neue Arzneimittel für Kleintiere 2018.

In 2018, two active pharmaceutical ingredients were released on the German market for small animals: the ectoparasiticide of the isoxazoline group Lotilaner (Credelio®) and the opioid analgesic Tramadol (Tralieve®). Two established veterinary active pharmaceutical ingredients became available for additional species: the nonsteroidal anti-inflammatory drug Meloxicam (Metacam®) from the oxicam group for guinea pigs and the inhalant anesthetic Sevoflurane (Sevoflo®) from the group of halogenated hydrocarbon compounds, which has additionally been authorized for cats. With the combination of Benzylpenicillin-Benzathine and Benzylpenicillin-Procaine, one temporarily non-available combination of active ingredients was reapproved in new drugs. Additionally, one drug with a new pharmaceutical form and one drug with a higher content of the active ingredient have been launched on the market for small animals.

Antibiotic treatment for newborns with congenital syphilis.

BACKGROUND: Congenital syphilis continues to be a substantial public health problem in many parts of the world. Since the first use of penicillin for the treatment of syphilis in 1943, which was a notable early success, it has remained the preferred and standard treatment including for congenital syphilis. However, the treatment of congenital syphilis is largely based on clinical experience and there is extremely limited evidence on the optimal dose or duration of administration of penicillin or the use of other antibiotics. OBJECTIVES: To assess the effectiveness and safety of antibiotic treatment for newborns with confirmed, highly probable and possible congenital syphilis. SEARCH METHODS: We searched the Cochrane STI Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, WHO ICTRP, ClinicalTrials.gov and Web of Science to 23 May 2018. We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing antibiotic treatment (any concentration, frequency, duration and route) with no intervention or any other antibiotic treatment for neonates with confirmed, highly probable or possible congenital syphilis. DATA COLLECTION AND ANALYSIS: All review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: Two RCTs (191 participants) met our inclusion criteria and none of these trials was funded by the industry. One trial (22 participants) compared benzathine penicillin with no intervention for infants with possible congenital syphilis. Low-quality evidence suggested that benzathine penicillin administration may not have decreased the rate of neonatal death due to any cause (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.06 to 11.70), and showed a possible reduction into the proportion of neonates with clinical manifestations of congenital syphilis (RR 0.12, 95% CI 0.01 to 2.09). Penicillin administration increased the serological cure at the third month (RR 2.13, 95% CI 1.06 to 4.27). These results should be taken with caution, because the trial was stopped early because there were four cases with clinical congenital syphilis in the no treatment group and none in the treatment group. Interim analysis suggested this difference was significant. This study did not report neonatal death due to congenital syphilis or the frequency of serious or minor adverse events after therapy. We downgraded the quality of evidence because of imprecision and risk of bias.One trial (169 participants) compared benzathine penicillin versus procaine benzylpenicillin. High- and moderate-quality evidence suggested that there were probably no differences between benzathine penicillin and procaine benzylpenicillin for the outcomes: absence of clinical manifestations of congenital syphilis (RR 1.00, 95% CI 0.97 to 1.03) and serological cure (RR 1.00, 95% CI 0.97 to 1.03). There were no cases of neonatal death due congenital syphilis; all 152 babies who followed up survived. This study did not report on the frequency of serious or minor adverse events after therapy. We downgraded the quality of evidence because of serious risk of bias. AUTHORS' CONCLUSIONS: At present, the evidence on the effectiveness and safety of antibiotic treatment for newborns with confirmed, highly probable or possible congenital syphilis is sparse, implying that we are uncertain about the estimated effect. One trial compared benzathine penicillin with no intervention for infants with possible congenital syphilis. Low-quality evidence suggested penicillin administration possibly reduce the proportion of neonates with clinical manifestations of congenital syphilis, penicillin administration increased the serological cure at the third month. These findings support the clinical use of penicillin in neonates with confirmed, highly probable or possible congenital syphilis. High- and moderate-quality evidence suggests that there are probably no differences between benzathine penicillin and procaine benzylpenicillin administration for the outcomes of absence of clinical manifestations of syphilis or serological cure.

Evaluation of plasma concentration after intravenous and intramuscular penicillin administration over 24 hr in healthy adult horses.

Penicillin is administered intravenously (IV) or intramuscularly (IM) to horses for the prevention and treatment of infections, and both routes have disadvantages. To minimize these shortcomings, a 24-hr hybrid administration protocol (HPP) was developed. Our objective was to determine penicillin plasma concentrations in horses administered via HPP. Venous blood was collected from seven healthy horses administered IV potassium penicillin G at 0 and 6 hr and IM procaine penicillin G at 12 hr. Blood was collected at 2-hr intervals from 0 to 20 hr and at 24 hr. Plasma penicillin concentrations were measured using liquid chromatography and mass spectrometry. Penicillin susceptibility from equine isolates was examined to determine pharmacodynamic targets. The MIC90 of penicillin for 264 isolates of Streptococcus sp. was ≤0.06 µg/ml. For the 24-hr dosing interval, the mean plasma penicillin concentration was >0.07 µg/ml. Five horses (72%) exceeded 0.06 µg/ml for 98% of the dosing interval, and two horses exceeded this value for 52%-65% of the dosing interval. The HPP achieved mean plasma penicillin concentrations in healthy adult horses above 0.07 µg/ml for a 24-hr dosing interval. However, individual variations in plasma concentrations were apparent and deserve future clinical study.

Microbial shifts in the swine nasal microbiota in response to parenteral antimicrobial administration.

The continuous administration of antimicrobials in swine production has been widely criticized with the increase of antimicrobial-resistant bacteria and dysbiosis of the beneficial microbial communities. While an increasing number of studies investigate the effects of antimicrobial administration on swine gastrointestinal microbiota biodiversity, the impact of their use on the composition and diversity of nasal microbial communities has not been widely explored. The objective of this study was to characterize the short-term impact of different parenteral antibiotics administration on the composition and diversity of nasal microbial communities in growing pigs. Five antimicrobial treatment groups, each consisting of four, eight-week old piglets, were administered one of the antimicrobials; Ceftiofur Crystalline free acid (CCFA), Ceftiofur hydrochloride (CHC), Tulathromycin (TUL), Oxytetracycline (OTC), and Procaine Penicillin G (PPG) at label dose and route. Individual deep nasal swabs were collected immediately before antimicrobial administration (control = day 0), and again on days 1, 3, 7, and 14 after dosing. The nasal microbiota across all the samples were dominated by Firmicutes, proteobacteria and Bacteroidetes. While, the predominant bacterial genera were Moraxella, Clostridium and Streptococcus. Linear discriminant analysis, showed a pronounced, antimicrobial-dependent microbial shift in the composition of nasal microbiota and over time from day 0. By day 14, the nasal microbial compositions of the groups receiving CCFA and OTC had returned to a distribution that closely resembled that observed on day 0. In contrast, pigs that received CHC, TUL and PPG appeared to deviate away from the day 0 composition by day 14. Based on our results, it appears that the impact of parenteral antibiotics on the swine nasal microbiota is variable and has a considerable impact in modulating the nasal microbiota structure. Our results will aid in developing alternative strategies for antibiotics to improve swine health and consequently production.

Impact of parenteral antimicrobial administration on the structure and diversity of the fecal microbiota of growing pigs.

While antimicrobials are cost-effective tools for prevention and treatment of infectious disease, the impact of their use on potentially beneficent mucosal microbial communities of growing pigs has not been widely explored. The objective of this study was to characterize the impact of parenteral antibiotics administration on the composition and diversity of the resident fecal microbiota in growing pigs. Five antimicrobial treatment groups, each consisting of four, eight-week old piglets, were administered one of the antimicrobials; Ceftiofur Crystalline free acid (CCFA), Ceftiofur hydrochloride (CHC), Oxytetracycline (OTC), Procaine Penicillin G (PPG) and Tulathromycin (TUL) at label dose and route. Individual fecal swabs were collected immediately before antimicrobial administration (control = day 0), and again on days 1, 3, 7, and 14 after dosing. Genomic DNA was extracted, and the V1-V3 hypervariable region of 16S rRNA gene was amplified and sequenced using Illumina Miseq-based sequencing. Across all groups, the most abundant phyla were Firmicutes, Bacteroidetes, and Proteobacteria. Linear discriminant analysis and stacked area graphs, showed a pronounced, antimicrobial-dependent shift in the composition of fecal microbiota over time from day 0. By day 14, the fecal microbial compositions of the groups receiving CHC and TUL had returned to a distribution that closely resembled that observed on day 0, but differences were still evident. In contrast, animals that received PPG, OTC and CCFA, showed a tendency towards a balanced homeostatic microbiota structure on day 7, but appeared to deviate away from the day 0 composition by day 14. Based on our results, the observed changes in fecal microbiota showed antimicrobial-specific variation in both duration and extent. Understanding the impact of these important antimicrobial-induced changes will be a critical step in optimizing the use of antimicrobials in health management programs in the swine industry.

Comparative therapeutic efficacy of Phyllanthus emblica (Amla) fruit extract and procaine penicillin in the treatment of subclinical mastitis in dairy buffaloes.

To investigate the comparative therapeutic efficacy of Phyllanthus emblica (Amla) fruit extract and procaine penicillin in the treatment of subclinical mastitis, a total of 30 subclinical mastitis positive buffaloes out of 194 lactating buffaloes were divided into 3 equal groups viz. A, B and C. Group A was treated with procaine penicillin, group B was treated with Phyllanthus emblica fruit extract and group C was served as control for 5 days respectively. The collected milk samples were subjected to the treatment trials before and after the treatment at day 0, 7th and 14th day aseptically. The evaluation parameters were bacteriological cure rate, milk pH, milk yield. The percentage cure rate of sub-clinically mastitic quarters in group A, B and C were 80.95%, 64.7% and 22.22% at day 14 respectively. The quarter based bacteriological cure rate was highest in group A (80.95%) followed by group B (64.7%) and group C (22.22%). The pH was significant (P > .05) in group A, B and C at day 0, 7 and 14. It is concluded that Phyllanthus emblica fruit extract is an inexpensive source in the treatment of subclinical mastitis in dairy buffaloes and can be used as an alternative to antibiotic therapy as for procaine penicillin.

Acute myocardial infarction in a patient suffering from penicillin-induced laryngeal edema : Kounis syndrome aggravated by adrenaline.

Kounis syndrome or allergic angina is defined as the coincidental occurrence of chest pain and allergic reactions accompanied by clinical and laboratory findings of classical angina pectoris. It is triggered by the action of potent vasoactive and inflammatory mediators, which are released from the mast cells during the allergic reaction. Epinephrine is a life-saving medication in anaphylaxis; however, it can aggravate ischemia and induce coronary vasospasm and arrhythmias. Here, we present a patient with Kounis syndrome that was caused by intramuscular injection of procaine penicillin G, and in whom epinephrine administration for treatment of laryngeal edema had provoked severe myocardial ischemia.

Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial.

BACKGROUND: Parenteral antibiotic therapy for young infants (aged 0-59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection. METHODS: We undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0-59 days) who either presented at a primary health-care clinic or were identified by a community health worker with signs of clinical severe infection. We included infants who were not critically ill and whose family refused admission. We randomly assigned infants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oral amoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome was treatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimental treatments as efficacious as the reference if the upper bound of the 95% CI for the difference in treatment failure was less than 5·0. This trial is registered at ClinicalTrials.gov, number NCT01027429. FINDINGS: Between Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%) were enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in the per-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillin and gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and 817 (753 per protocol) were assigned procaine benzylpenicillin, gentamicin, and amoxicillin. Treatment failure within 7 days of enrolment was reported in 90 (12%) infants who received procaine benzylpenicillin and gentamicin (reference), 76 (10%) of those given amoxicillin and gentamicin (risk difference with reference -1·9, 95% CI -5·1 to 1·3), and 99 (13%) of those treated with procaine benzylpenicillin, gentamicin, and amoxicillin (risk difference with reference 1·1, -2·3 to 4·5). INTERPRETATION: Two simplified antibiotic regimens requiring fewer injections are equivalent to a reference treatment for young infants with signs of clinical severe infection but without signs of critical illness. The use of these simplified regimens has the potential to increase access to treatment for sick young infants who cannot be referred to hospital. FUNDING: The Saving Newborn Lives initiative of Save the Children, through support from the Bill & Melinda Gates, and by WHO and USAID.

Residual volume in vials of antibiotics used in pediatrics / Volumen residual de antibióticos en frascos-ampolla utilizados en pediatría / Volume residual de antibióticos em frascos-ampola utilizados na pediatria

Abstract OBJECTIVE Quantifying residual volume contained in vials of antibiotics used in pediatrics. METHOD This is an experiment involving samples from vials of antibiotics used in a pediatric hospital. Residual volume was identified by calculating the difference in weight measurement before and after the vials were washed. Evaluation of the residual volume difference in the vials was determined by the Wilcoxon non-parametric test for a sample and established at a significance level of 5%. RESULTS 105 samples of antibiotics were selected. The correct use of the antibiotics oxacillin (88.57%) and ceftriaxone (94.28%) predominated with low residual values. The same did not occur for procaine benzylpenicillin + potassium benzylpenicillin, since a greater residual volume was discarded in 74.28% of the vials. CONCLUSION We highlight the need for improvements in managing antibiotics in the institution under study, so that the excess volume of the antibiotics in the vials is used within the acceptable stable time. It is also necessary that the disposal of the residual volume be adequately disposed, since it presents a risk to public health and the environment.

Resumen OBJETIVO Cuantificar el volumen residual contenido en frascos-ampolla de antibióticos utilizados en pediatría. MÉTODO Se trata de un experimento con muestras de frascos-ampolla de antibióticos utilizados en hospital pediátrico. El volumen residual fue identificado calculándose la diferencia de la verificación del peso antes y después del lavado del frasco-ampolla. La evaluación de la diferencia de los volúmenes residuales en los frascos-ampolla fue determinada por la prueba no paramétrica de Wilcoxon para una muestra y establecido el nivel de significación del 5%. RESULTADOS Fueron seleccionadas 105 muestras de antibióticos. Predominó el correcto aprovechamiento de los antibióticos oxacilina (88,57%) y ceftriaxona (94,28%), con bajos valores residuales. Lo mismo no ocurrió con la bencilpenicilina procaína + potásica, pues en el 74,28% de los frascos hubo descarte de volumen residual superior. CONCLUSIÓN Se destaca la necesidad de mejorías en la gestión de los antibióticos en la institución en estudio, a fin de que el volumen excedente del antibiótico en frasco-ampolla se aproveche hasta el tiempo de estabilidad permitido, así como es necesario que haya la adecuación de la manera de descarte del volumen residual, que presenta riesgo a la salud pública y al medio ambiente.

Resumo OBJETIVO Quantificar o volume residual contido em frascos-ampola de antibióticos utilizados na pediatria. MÉTODO Trata-se de um experimento com amostras de frascos-ampola de antibióticos utilizados em hospital pediátrico. O volume residual foi identificado calculando-se a diferença da aferição do peso antes e após a lavagem do frasco-ampola. A avaliação da diferença dos volumes residuais nos frascos-ampola foi determinada pelo teste não paramétrico de Wilcoxon para uma amostra e estabelecido o nível de significância de 5%. RESULTADOS Foram selecionadas 105 amostras de antibióticos. Predominou o correto aproveitamento dos antibióticos oxacilina (88,57%) e ceftriaxona (94,28%), com baixos valores residuais. O mesmo não ocorreu com a benzilpenicilina procaína + potássica, pois em 74,28% dos frascos houve descarte de volume residual superior. CONCLUSÃO Destaca-se a necessidade de melhorias na gestão dos antibióticos na instituição em estudo, para que o volume excedente do antibiótico em frasco-ampola seja aproveitado até o tempo de estabilidade permitido, assim como é necessário que haja a adequação da forma de descarte do volume residual, que apresenta risco à saúde pública e ao meio ambiente.