Combination Of Penicillin Research Articles

Synergistic oral beta-lactam combinations for treating tuberculosis.

The enormous burden of tuberculosis (TB) worldwide is a major challenge to human health, but the costs and risks associated with novel drug discovery have limited treatment options for patients. Repurposing existing antimicrobial drugs offers a promising avenue to expand TB treatment possibilities. This study aimed to explore the activity and synergy of beta-lactams in combination with a beta-lactamase inhibitor, which have been underutilized in TB treatment to date. Based on inhibitory concentration, oral bioavailability, and commercial availability, seven beta-lactams (cefadroxil, tebipenem, cephradine, cephalexin, cefdinir, penicillin V, and flucloxacillin), two beta-lactamase inhibitors (avibactam and clavulanate), and three second-line TB drugs (moxifloxacin, levofloxacin, and linezolid) were selected for combination in vitro testing against Mycobacterium tuberculosis H37Rv. Resazurin assays and colony forming unit enumeration were used to quantify drug efficacy, Chou-Talalay calculations were performed to identify drug synergy and Chou-Martin calculations were performed to quantify drug dose reduction index. The order of activity of beta-lactams was cefadroxil>tebipenem>cephradine>cephalexin>cefdinir>penicillin V>flucloxacillin. The addition of clavulanate improved beta-lactam activity to a greater degree than the addition of avibactam. As a result, avibactam was excluded from further investigations, which focused on clavulanate. Synergy was demonstrated for cefdinir/cephradine, cefadroxil/tebipenem, cefadroxil/penicillin V, cefadroxil/cefdinir, cephalexin/tebipenem, cephalexin/penicillin V, cephalexin/cefdinir, cephalexin/cephradine, and cefadroxil/cephalexin, all with clavulanate. However, combining beta-lactams with moxifloxacin, levofloxacin, or linezolid resulted in antagonistic effects, except for the combinations of penicillin V/levofloxacin, penicillin V/moxifloxacin, and cefdinir/moxifloxacin. Beta-lactam synergy may provide viable combination therapies for the treatment of TB.

Trends in Hospital Antibacterial Consumption in Belgium (2017-2021): Evaluating the Impact of the COVID-19 Pandemic

This study aimed to evaluate the impact of the COVID-19 pandemic on antimicrobial consumption (AMC) in Belgian hospitals from 2017 to 2021, using data from the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) and the Belgian Hospitals Surveillance of Antimicrobial Consumption (BeH-SAC). Antimicrobial volume was quantified in Defined Daily Doses (DDDs), and AMC was expressed in DDDs/1000 inhabitants/day (DIDs), DDDs/1000 patient days and DDDs/1000 admissions. Linear regressions were employed to analyze 5-year trends for the ATC J01 group, at the ATC-3 level and for broad-spectrum antimicrobials. Broad-spectrum antibiotics included combinations of penicillins, incl. beta-lactamase inhibitors (J01CR), second-generation cephalosporins (J01DC), third-generation cephalosporins (J01DD), macrolides, lincosamides and streptogramins (J01F, excluding erythromycin J01FA01), and fluoroquinolones (J01MA). The compound annual growth rate (CAGR) calculated for the years preceding the pandemic was used to forecast 2020 and 2021 AMC, enabling a comparison with the actual use. Hospital AMC measured as DIDs decreased by 12% from 2019 to 2020. In contrast, when expressed as DDDs/1000 patient days and DDDs/1000 admissions, a 5% and 7% increase was observed, respectively. Antibacterials for systemic use (J01) showed a significant decrease over the 5 years only when expressed in DIDs. Notable trends included a negative trend for quinolone antibacterials (J01M) when expressed in the three incidence units, as for amphenicols (J01B) when using hospital denominators only. Positive trends were observed for sulfonamides and trimethoprim (J01E) using hospital denominators and for other beta-lactam antibacterials (J01D) with the ‘patient days’ denominator. While the consumption of all J01 antimicrobial subclasses deviated negatively from predicted use both in 2020 and 2021 when expressed in DIDs, positive deviations were recorded using hospital denominators, except for macrolides (J01F). The use of broad-spectrum antimicrobials showed a notable decrease between 2017 and 2021 when expressed in DIDs. However, when using hospital denominators, the observed use of broad-spectrum antimicrobials exceeded the forecasted values in 2020, to regress below the forecasted levels in 2021 (Figure 1). Contrary to results obtained using the widely applied country’s population as the denominator, a notable surge in AMC, particularly for broad-spectrum antimicrobials, was observed in 2020 when using hospital-specific denominators. This increase coincided with the onset of the COVID-19 crisis. These findings emphasize the need for a national hospital surveillance system that uses denominators that accurately represent the specific population being monitored. Implementing robust hospital-specific surveillance mechanisms would improve the precision of evaluations and facilitate targeted interventions aimed at optimizing antimicrobial utilization.

Myiasis in a Backyard Pig: A Case Report

Background: Myiasis is a parasitic infestation of livestock animals caused by dipteran larvae. The presence of wounds, lack of hygiene on the farm, and temperate climatic conditions contribute to myiasis. Swine can be infested by myiasis if injured pigs are not treated properly and failure to treat myiasis in time may cause the culling or death of the pigs, resulting in huge economic loss to the farmers. But like humans and other farm animals, pigs also deserve to be treated and cured of any suffering or disease. Therefore, this study is documented on pig myiasis and its management because to date a few cases have been reported on it. Case presentation: This case report documented the successful management of neck myiasis in a male, 9-month-old, 12-kg-weighing backyard pig. The wound site was cleaned using antiseptics and maggots were removed. The site was treated with turpentine oil, and ivermectin at 0.2 mg/kg B.W. and S/C. A combination of streptomycin (12.5 mg/kg B.W.) and penicillin (20000 IU/kg B.W.) was used IM daily for 5 days to prevent secondary bacterial infection. The wound was dressed regularly on every alternate day until the complete removal of maggots and the formation of granulation tissue. Conclusion: Through proper therapeutic management, the backyard pig’s neck myiasis wound was successfully healed in 10 days without any complications.

Actinomycosis presenting as a nasopharyngeal mass: A case report

Actinomycetes are predominantly pathogenic bacteria that lack aerial hyphae and do not form spores. They are generally anaerobic or facultative anaerobic Gram-positive bacteria, belonging to the prokaryotic group. Actinomycetes are widely distributed in nature, similar to other bacteria, and are mostly saprophytic, with a few being parasitic. They are named as such due to their colony's radial form. The symptoms and signs of actinomycosis are atypical and rarely manifest in the nasopharynx. Consequently, it can be challenging to distinguish actinomycosis from nasopharyngeal carcinoma, making diagnosis difficult. Histopathology is usually relied upon for diagnosis, although culture may pose challenges. Fortunately, actinomycetes are highly sensitive to penicillin. Therefore, timely treatment with high doses of penicillin is crucial for successful recovery. In this case study, we present the details of a 53-year-old female patient with no history of mucosal damage or tooth decay but with a previous partial thyroidectomy. The patient experienced recurring neck pain accompanied by progressive limitation of neck movement. Nasopharyngoscopy revealed the presence of a smooth-surfaced mass. Subsequent biopsy, clinical imaging, microbiological analysis, and histological findings confirmed the diagnosis of actinomycosis.Following a comprehensive treatment plan involving a combination of penicillin and doxycycline for a duration of two months, the disease was successfully eradicated.

Impact of an antimicrobial stewardship program indicator on the appropriateness of the empiric antibiotic treatment of urinary source Escherichia coli bacteraemia

A prospective multicentre study was carried out between 2017 and 2021 to assess (1) the appropriateness of the empirical treatment to the local guidelines of urinary source Escherichia coli bacteraemia, (2) the appropriateness of empirical treatment to antibiotic sensitivity results and (3) the degree of error in the local guidelines regarding the antibiotic sensitivity reported in acute care hospitals enrolled in the vigilància de les infeccions relacionades amb l'atenció sanitària de Catalunya program. During the study period, 79.0% of the empirical treatments analysed complied with the guidelines and 88.1% were appropriate in view of the in vitro activity of the isolated strain. The rate of appropriateness rose from 73.8% in 2017 to 81.0% in 2021 (P < 0.001). The degree of error in the recommendations regarding the in vitro activity of the isolated strains was 5.9% and remained stable during the study period. Antibiotic families correctly prescribed according to the guidelines were third-generation cephalosporins (54.9%), carbapenems (16.8%) and combinations of penicillins and beta-lactamase inhibitors (16.4%). Of the 8009 E. coli strains, 19.0% were extended-spectrum beta-lactamases producers, 36.8% were resistant to quinolones and 0.5% were resistant to carbapenems. The broad implementation of an antimicrobial stewardship program with quality indicators of antibiotic use improved compliance to local guidelines in the empiric treatment of urinary tract E. coli bacteraemia. The degree of error in local guidelines was low but higher in more complex hospitals and in healthcare-associated infections. Guidelines need to be constantly updated with the use of epidemiological data, rapid diagnostic tests and the analysis of patient risk factors specific to each geographical area.

Rare case of septic shock combined with meningitis caused by Pasteurella multocida without a history of cat and dog bites

BackgroundPasteurella multocida is a zoonotic pathogen that mainly causes local skin and soft tissue infections in the human body through cat and dog bites. It rarely causes bacteraemia (or sepsis) and meningitis. We reported a case of septic shock and meningitis caused by P. multocida in a patient without a history of cat and dog bites.Case presentationAn 84-year-old male patient was urgently sent to the emergency department after he was found with unclear consciousness for 8 h, accompanied by limb tremors and urinary incontinence. In the subsequent examination, P. multocida was detected in the blood culture and wound secretion samples of the patient. However, it was not detected in the cerebrospinal fluid culture, but its DNA sequence was detected. Therefore, the patient was clearly diagnosed with septic shock and meningitis caused by P. multocida. The patient had no history of cat or dog contact or bite. The patient was subsequently treated with a combination of penicillin G, doxycycline, and ceftriaxone, and he was discharged after 35 days of hospitalisation.ConclusionThis report presented a rare case of septic shock and meningitis caused by P. multocida, which was not related to a cat or dog bite. Clinical doctors should consider P. multocida as a possible cause of sepsis or meningitis and should be aware of its potential seriousness even in the absence of animal bites.

Antibiotic therapy in pediatric outpatient ENT infections

Inflammatory diseases of the ENT organs are currently the most common pathology in children. Diseases of the nasal cavity and paranasal sinuses occupy the leading place in the structure of primary morbidity, averaging 55.5%. In the paediatric population, ENT pathology develops more often as a secondary bacterial complication of a previous viral infection of the upper respiratory tract. Bacterial otorhinolaryngological complications often require the prescription of antibacterial drugs. In outpatient practice, the choice of rational and safe therapy is of utmost importance. The article presents clinical cases of ENT diseases in children and algorithms for the choice of initial antibacterial therapy. Recommended drugs for the treatment of ENT diseases and the main indications for their administration are presented. Most national and international guidelines recommend amoxicillin as a first-line drug for the treatment of major respiratory pathogens (S. pneumoniae, H. influenzae, S. pyogenes) and bacterial complications of ENT diseases in children, taking into account its low toxicity, cost and convenient form of administration. In case of ineffective therapy or in the presence of risk factors for drug resistance of pathogens, semi-synthetic penicillins in combination with β-lactamase inhibitors are recommended.

Hospital Antibiotic Consumption before and during the COVID-19 Pandemic in Hungary.

The aim of this study was to assess antibiotic use in the Hungarian hospital care sector during and before the pandemic. Aggregated systemic antibiotic (ATC: J01) utilisation data were obtained for the 2010-2021 period. Classifications and calculations were performed according to the WHO ATC/DDD index and expressed as DDD per 1000 inhabitants and per day (DID), DDD per 100 patient-days (DHPD) and DDD/discharge. A linear regression (trend analysis) was performed for the pre-COVID years (2010-2019) and a prediction interval was set up to assess whether the pandemic years' observed utilisation fit in. Antibiotic utilisation was constant in DID before and during the pandemic (2019: 1.16; 2020: 1.21), while we observed a substantial increase in antibiotic use when expressed in DDD per 100 patient-days (2019: 23.3, 2020: 32.2) or DDD/discharge (2019: 1.83, 2020: 2.45). The observed utilisation level of penicillin combinations; first-, third- and fourth-generation cephalosporins; carbapenems; glycopeptides; nitroimidazoles and macrolides exceeded the predicted utilisation values in both pandemic years. Before the pandemic, co-amoxiclav headed the top list of antibiotic use, while during the pandemic, ceftriaxone became the most widely used antibiotic. Azithromycin moved up substantially on the top list of antibiotic use, with a 397% increase (2019: 0.45; 2020: 2.24 DHPD) in use. In summary, the pandemic had a major impact on the scale and pattern of hospital antibiotic use in Hungary.

Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform

Antimicrobial resistance (AMR) has become a global health crisis in need of novel solutions. To this end, antibiotic combination therapies, which combine multiple antibiotics for treatment, have attracted significant attention as a potential approach for combating AMR. To facilitate advances in antibiotic combination therapies, most notably in investigating antibiotic interactions and identifying synergistic antibiotic combinations however, there remains a need for automated high-throughput platforms that can create and examine antibiotic combinations on-demand, at scale, and with minimal reagent consumption. To address these challenges, we have developed a Robotic-Printed Combinatorial Droplet (RoboDrop) platform by integrating a programmable droplet microfluidic device that generates antibiotic combinations in nanoliter droplets in automation, a robotic arm that arranges the droplets in an array, and a camera that images the array of thousands of droplets in parallel. We further implement a resazurin-based bacterial viability assay to accelerate our antibiotic combination testing. As a demonstration, we use RoboDrop to corroborate two pairs of antibiotics with known interactions and subsequently identify a new synergistic combination of cefsulodin, penicillin, and oxacillin against a model E. coli strain. We therefore envision RoboDrop becoming a useful tool to efficiently identify new synergistic antibiotic combinations toward combating AMR.

Antibiotic prophylaxis and hospitalization of horses subjected to median laparotomy: gut microbiota trajectories and abundance increase of Escherichia.

Horse clinics are hotspots for the accumulation and spread of clinically relevant and zoonotic multidrug-resistant bacteria, including extended-spectrum β-lactamase producing (ESBL) Enterobacterales. Although median laparotomy in cases of acute equine colic is a frequently performed surgical intervention, knowledge about the effects of peri-operative antibiotic prophylaxis (PAP) based on a combination of penicillin and gentamicin on the gut microbiota is limited. We collected fecal samples of horses from a non-hospitalized control group (CG) and from horses receiving either a pre-surgical single-shot (SSG) or a peri-operative 5-day (5DG) course of PAP. To assess differences between the two PAP regimens and the CG, all samples obtained at hospital admission (t0), on days three (t1) and 10 (t2) after surgery, were screened for ESBL-producing Enterobacterales and subjected to 16S rRNA V1-V2 gene sequencing. We included 48 samples in the SSG (n = 16 horses), 45 in the 5DG (n = 15), and 20 in the CG (for t0 and t1, n = 10). Two samples of equine patients receiving antibiotic prophylaxis (6.5%) were positive for ESBL-producing Enterobacterales at t0, while this rate increased to 67% at t1 and decreased only slightly at t2 (61%). Shannon diversity index (SDI) was used to evaluate alpha-diversity changes, revealing there was no significant difference between horses suffering from acute colic (5DG, SDImean of 5.90, SSG, SDImean of 6.17) when compared to the CG (SDImean of 6.53) at t0. Alpha-diversity decreased significantly in both PAP groups at t1, while at t2 the onset of microbiome recovery was noticed. Although we did not identify a significant SDImean difference with respect to PAP duration, the community structure (beta-diversity) was considerably restricted in samples of the 5DG at t1, most likely due to the ongoing administration of antibiotics. An increased abundance of Enterobacteriaceae, especially Escherichia, was noted for both study groups at t1. Colic surgery and PAP drive the equine gut microbiome towards dysbiosis and reduced biodiversity that is accompanied by an increase of samples positive for ESBL-producing Enterobacterales. Further studies are needed to reveal important factors promoting the increase and residency of ESBL-producing Enterobacterales among hospitalized horses.

Preplacing tarsorrhaphy sutures for bulbus oculi proptosis in Pomeranian dogs

Proptosis of the bulbus oculi is a disorder of the eyeball protruding from the orbit, which generally occurs due to trauma. This paper reports the treatment of bulbus oculi proptosis in Pomeranian dogs using tarsorrhaphy. Tarsorrhaphy is a surgical procedure used to unite part or all of the upper and lower eyelids to close part or all of the eyes. After tarsorrhaphy, the dog was administered an antibiotic combination of penicillin and streptomycin, anti-inflammatory and analgesic meloxicam, and fluid therapy using Ringer's lactate. The antibiotic amoxicillin/clavulanic acid and the blood-boosting drug Fufang E'jiao Jiang were administered orally for 14 days after tarsorrhaphy as prophylactic treatment. Methylprednisolone was also administered orally as an anti-inflammatory agent for 3 days after tarsorrhaphy. Hospitalization was performed for 24 h, and during observation, discharge was observed in the tarsorrhaphy area. Weekly monitoring at the clinic is recommended for owners to observe the condition of the dog’s eyes and tarsorrhaphy sutures

Antibiotic prescribing to inpatients in Limpopo, South Africa: a multicentre point-prevalence survey

BackgroundElectronic continuous surveillance databases are ideal for monitoring antibiotic use (ABU) in hospitalised patients for antibiotic stewardship programmes (ASP). However, such databases are scarce in low-resource settings. Point prevalence surveys (PPS) are viable alternatives. This report describes ABU and identifies ASP implementation improvement areas in Limpopo Province, South Africa.MethodsThis cross-sectional descriptive study extracted patient-level ABU data from patients’ files using a modified global PPS tool. Data were collected between September and November 2021 at five regional hospitals in Limpopo Province, South Africa. All patients in the wards before 8 a.m. on study days with an antibiotic prescription were included. Antibiotic use was stratified by Anatomic Therapeutic Chemical and Access, Watch, Reserve classifications and presented as frequencies and proportions with 95% confidence intervals (CI). Associations between categorical variables were assessed using the chi-square test. Cramér’s V was used to assess the strength of these associations.ResultsOf 804 inpatients surveyed, 261 (32.5%) (95% CI 29.2–35.7) were prescribed 416 antibiotics, 137 were female (52.5%) and 198 adults (75.9%). One hundred and twenty-two (46.7%) patients received one antibiotic, 47.5% (124/261) received two, and 5.7% (15/261) received three or more antibiotics. The intensive care units had a higher ABU (68.6%, 35/51) compared to medical (31.3%, 120/384) and surgical (28.5%, 105/369) wards (p = 0.005, Cramér’s V = 0.2). Lower respiratory tract infection (27.4%, 104/379), skin and soft tissue infections (SST) (23.5%, 89/379), and obstetrics and gynaecology prophylaxis (14.0%, 53/379) were the common diagnoses for antibiotic prescriptions. The three most prescribed antibiotic classes were imidazoles (21.9%, 91/416), third-generation cephalosporins (20.7%, 86/416) and combination penicillin (18.5%, 79/416). Access antibiotics accounted for 70.2% (292/416) of prescriptions and Watch antibiotics for 29.6% (123/416) (p = 0.110, Cramér’s V = 0.1). Reasons for prescribing and treatment plans were documented in 64.9% (270/416) (95% CI 60.3–69.5) and 21.4% (89/416) (95% CI 17.3–25.3) of prescriptions, respectively.ConclusionsThe study serves as a baseline for ABU surveillance at the five regional hospitals in Limpopo Province. Lack of documentation indicates poor prescribing practices; ASP should address gaps by deploying evidence-based, multifaceted and stepwise interventions.

Effect of a national antibiotic stewardship intervention in China targeting carbapenem overuse: An interrupted time-series analysis

To assess trends and patterns of carbapenem use and to evaluate the effects of a nationwide antibiotic stewardship policy to reduce carbapenem overuse. In this quasi-experimental study, using longitudinal data from the national drug procurement database and interrupted time-series analyses with carbapenems as the intervention group and possible carbapenem substitutes as the comparison group, we evaluated the effects of a national stewardship policy on carbapenem consumption and expenditures, by region and types of healthcare institutions. The carbapenem procurement volume declined by -28.8% (95% CI -35.0 to -22.6) (-334.4 thousand defined daily doses [DDDs] per month), and carbapenem expenditures showed a relative reduction of -38.1% (-43.9 to -32.2). The gap between the use of carbapenems and each drug in the comparison group narrowed after the policy intervention, with an increase in tigecycline use (14.9 thousand DDDs [10.8-18.9]) and a slower decrease in use of certain third-generation cephalosporin combinations (-85.7 [-143.0 to -28.4]), penicillin combinations (-200.9 [-421.4-19.6]), and fourth-generation cephalosporins (-116.9 [-219.8 to -14.0]). Consumption was highest during the pre-policy period, and declines were largest following the intervention in the eastern region (-32.1%, -39.8 to -24.4) and among tertiary hospitals (-266.2 [-339.5 to -192.9] thousand DDDs per month). This population-level drug utilization research represents the first comprehensive evaluation of the effectiveness of China's nationwide carbapenem stewardship. The national policy targeting carbapenem prescribing has led to a sustained reduction in carbapenem use with limited substitution. Effects varied geographically and were concentrated in tertiary and secondary hospitals.

Prescribing Pattern of Antibiotics among Hospitalized Patients with Urinary Tract Infection.

Urinary tract infection is one of the most common bacterial infections worldwide. It has become one of the most common cause for the hospitalization and sepsis. It is generally treated with antimicrobial agents and fluids. This study was conducted to study the prescribing pattern of antibiotic among hospitalized patients with urinary tract infection. A descriptive cross-sectional study was conducted in Nepal Medical College Teaching Hospital, Attarkhel, Kathmandu from January 2022 to April 2022. Patients aged 18 years or above of both sex, admitted to various departments with the provisional diagnosis of urinary tract infection prescribed with antibiotics were included in the study. Out of 146 patients admitted with a diagnosis of urinary tract infection, the most commonly prescribed antibiotics during hospital stay were cephalosporin in 102 (69.9%) patients followed by combination of penicillin and beta-lactamase inhibitors (31, 21.2%) and fluoroquinolones (15, 10.3%). Ceftriaxone (78, 53.4%) alone was the most commonly prescribed antibiotic as empirical therapy followed by combination of piperacillin and tazobactam (22, 15.1%). One hundred and forty four (78.6%) patients were prescribed antibiotics from the watch group followed by the access group (21, 11.5 %). E. coli was the most common organism isolated in 29 (76.3%) patients. Cephalosporin was the commonest antibiotic group prescribed in hospitalized patients among which ceftriaxone was commonly prescribed as an empirical therapy. Among AWaRe classification, antibiotics from the watch group were commonly prescribed.

Analysis of Antibiotic Exposure and Development of Acute Graft-vs-Host Disease Following Allogeneic Hematopoietic Cell Transplantation

Certain antibiotic exposures have been associated with increased rates of acute graft-vs-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT). Since antibiotic exposure can both affect and be affected by infections, analyzing time-dependent exposure in the presence of multiple potential confounders, including prior antibiotic exposures, poses specific analytical challenges, necessitating both a large sample size and unique approaches. To identify antibiotics and antibiotic exposure timeframes associated with subsequent aGVHD. This cohort study assessed allo-HCT at a single center from 2010 to 2021. Participants included all patients aged at least 18 years who underwent their first T-replete allo-HCT, with at least 6 months of follow-up. Data were analyzed from August 1 to December 15, 2022. Antibiotics between 7 days before and 30 days after transplant. The primary outcome was grade II to IV aGVHD. The secondary outcome was grade III to IV aGVHD. Data were analyzed using 3 orthogonal methods: conventional Cox proportional hazard regression, marginal structural models, and machine learning. A total of 2023 patients (median [range] age, 55 [18-78] years; 1153 [57%] male) were eligible. Weeks 1 and 2 after HCT were the highest-risk intervals, with multiple antibiotic exposures associated with higher rates of subsequent aGVHD. In particular, exposure to carbapenems during weeks 1 and 2 after allo-HCT was consistently associated with increased risk of aGVHD (minimum hazard ratio [HR] among models, 2.75; 95% CI, 1.77-4.28), as was week 1 after allo-HCT exposure to combinations of penicillins with a β-lactamase inhibitor (minimum HR among models, 6.55; 95% CI, 2.35-18.20). In this cohort study of allo-HCT recipients, antibiotic choices and schedules in the early course of transplantation were associated with aGVHD rates. These findings should be considered in antibiotic stewardship programs.

In vitro reduction of Escherichia coli biofilm mass by platelet-rich plasma lysate (PRP-L)

Placentitis-induced, pre-term fetal loss has caused hardships and financial losses to the equine breeding industry for decades. While traditional multi-modal treatments including a combination of gentamicin, penicillin, altrenogest, firocoxib, and pentoxifylline can sometimes prolong gestation and neonatal survival, treatment failures still occur and antibiotic therapy can be quite lengthy. Understanding potential biofilms in these reproductive infections uncovers a pitfall to the success of traditional treatment options: antimicrobials are ineffective at penetrating and killing biofilms in vitro and in vivo. Platelet-rich plasma lysate (PRP-L) is increasingly accepted as an adjunctive treatment option for biofilm associated infections across species. The aim of this study was to evaluate the reduction in biofilm formation of 10 isolates of Escherichia coli collected from the equine uterus. Isolates were stored in glycerol at -80°C; each isolate including a positive (ATCC 25922) and negative (ATCC BAA 2469) strain, was cultured for 18-24 h at 33-37°Cin ambient air until bacterial colonies were visible. A suspension of each isolate, adjusted to a 0.5 McFarland value, was used to inoculate a tissue culture treated, round-bottom 96-well microtiter plate incubated under microaerophilic orbital shaking conditions for 18-24 h at 33-37°C. Following incubation, with or without PRP-L, the supernatant was removed, wells were stained with 0.03% crystal violet for 15 minutes at room temperature with orbital shaking, rinsed to remove excess stain, solubilized with ethanol, and absorbance optical density (OD570) read with a plate reader. The range in reduction of biofilm mass with PRP-L treatment was 48 – 84%, with an average of 60%. In conclusion, the results suggest that comparison of a traditional multi-modal therapy for placentitis with a multi-modal therapy augmented with PRP-L has the potential to finally improve placentitis outcomes and reduce the length of antibiotic treatment, but further in vivo evaluation of this approach is required.

Effect of treatment with benzathine penicillin combined with ceftriaxone in elderly patients with latent syphilis

Purpose: To investigate the effect of the combination of benzathine penicillin and ceftriaxone in the treatment of latent syphilis in the elderly. &#x0D; Methods: A total of 70 elderly patients with latent syphilis treated in the First People’s Hospital of Yichang from March 2020 to March 2021 were enrolled in this study. Control group (CG) comprised thirty-two patients treated with benzathine penicillin, while 38 patients received the combination of benzathine penicillin and ceftriaxone were placed in the study group (SG). Therapeutic efficacy and adverse reactions in both groups were assessed. The difference in toludine red unheated serum test (TRUST) negative conversion rate at different periods of treatment (3, 6, and 12 months) after treatment was observed. Dermatological quality of life index (DLQI), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores were also determined before and after treatment. &#x0D; Results: Total efficacy in the study group was significantly higher than that in the control group after treatment (p &lt; 0.05), but there was no significant difference in the total incidence of adverse reactions between both groups (p &gt; 0.05). The TRUST negative conversion rate at 6 and 12 months in SG was higher than that in CG (p &lt; 0.05), while DLQI, SAS and SDS scores in SG were significantly lower after treatment (p &lt; 0.05). &#x0D; Conclusion: Treatment of elderly patients with latent syphilis with the combination of benzathine penicillin and ceftriaxone effectively controls the disease and improves patients’ negative emotions and quality of life with few adverse drug reactions. Further clinical trials are required prior to application in clinical practice.

COVID-19 pandemic and the quality of antibiotic use in primary care: an interrupted time-series study.

The coronavirus disease-19 pandemic and the related public health mitigation measures have impacted the transmission of infectious diseases; however, their impact on the use of antibacterials has not yet been extensively evaluated. This study evaluated the impact of the pandemic on the consumption patterns of antibacterials for systemic use in primary care in Portugal. An interrupted time-series analysis was performed using the autoregressive integrated moving average model of the antibacterials dispensed in the community pharmacies in Portugal from 1 January 2016 to 30 June 2022. Monthly rates of absolute consumption (all antibacterials for systemic use, and specifically penicillins; cephalosporins; macrolides, lincosamides, and streptogramins; and quinolones) and the relative consumption of antibacterials (penicillins sensitive to β-lactamase, penicillin combinations including β-lactamase inhibitors, third- and fourth-generation cephalosporins, fluoroquinolones, and the ratio of broad- to narrow-spectrum antibacterials) were estimated. Antibiotic consumption was expressed in defined daily doses per 1000 inhabitants per day (DID). In Portugal, the consumption of antibacterials (J01) declined sharply immediately after the beginning of the pandemic, having a significant reduction of >5 DID (P < .0001). A similar, short-term impact was found for penicillins (-2.920 DID; P < .0001); cephalosporins (-0.428 DID; P < .0001); macrolides, lincosamides, and streptogramins (-0.681 DID; P = .0021); and quinolones (-0.320 DID; P < .0001). A long-term increase was found for cephalosporins (+0.019 DID per month; P < .0001). Relative consumption changes were only found for third- and fourth-generation cephalosporins (0.0734%). Our study suggests that the coronavirus disease-19 pandemic may have resulted in a decrease in antibiotic use, with no significant changes in the relative dispense. Uncertainties regarding the long-term effects of the pandemic and its impact on the rates of resistance remain.

Treatment of Enterococcus faecalis Infective Endocarditis: A Continuing Challenge.

Today, Enterococcus faecalis is one of the main causes of infective endocarditis in the world, generally affecting an elderly and fragile population, with a high mortality rate. Enterococci are partially resistant to many commonly used antimicrobial agents such as penicillin and ampicillin, as well as high-level resistance to most cephalosporins and sometimes carbapenems, because of low-affinity penicillin-binding proteins, that lead to an unacceptable number of therapeutic failures with monotherapy. For many years, the synergistic combination of penicillins and aminoglycosides has been the cornerstone of treatment, but the emergence of strains with high resistance to aminoglycosides led to the search for new alternatives, like dual beta-lactam therapy. The development of multi-drug resistant strains of Enterococcus faecium is a matter of considerable concern due to its probable spread to E. faecalis and have necessitated the search of new guidelines with the combination of daptomycin, fosfomycin or tigecycline. Some of them have scarce clinical experience and others are still under investigation and will be analyzed in this review. In addition, the need for prolonged treatment (6-8 weeks) to avoid relapses has forced to the consideration of other viable options as outpatient parenteral strategies, long-acting administrations with the new lipoglycopeptides (dalbavancin or oritavancin), and sequential oral treatments, which will also be discussed.

Within State Variability of Antimicrobial Susceptibility: Missouri as an Archetype to Assess Guidelines for Antimicrobial Prophylaxis for Transurethral Procedures

To evaluate variability among hospitals in susceptibility of common uropathogens to antimicrobial agents frequently used in transurethral procedures in order to examine whether state-based guidelines might be more appropriate than national prophylactic guidelines. Hospital-level antibiograms were requested from all hospitals throughout the state of Missouri. We studied Escherichia coli, Klebsiella, and Proteus sensitivities to evaluate common guideline recommended antimicrobials including trimethoprim sulfamethoxazole (TMP-SMX), third-generation cephalosporins, cefazolin, penicillin combinations, gentamicin, and fluoroquinolones. We evaluated variability and association between hospital characteristics and antimicrobial sensitivities. Data was requested from 81 hospitals across the state and 38 provided the requested data (47% response rate). Susceptibility was highest for third-generation cephalosporins for E. coli (mean of 94%), Proteus (96%), and Klebsiella (96%). Gentamicin also had high susceptibility for the bacteria studied; 94% for E. coli and 96% for Klebsiella. Current first line recommended agents showed more modest coverage for E. coli (cefazolin 84%, TMP-SMX 78%), Proteus (cefazolin 82%, TMP-SMX 71%), and Klebsiella (cefazolin 90%, TMP-SMX 89%). Post transurethral procedure infections are common. Rates can be limited with appropriate prophylaxis. Deciding on empirical coverage must take into account local resistance patterns. There is substantial variability among and within states in antimicrobial susceptibility for common uropathogens. When selecting antimicrobial prophylaxis, urologists should consider local- rather than state- or nation-level antibiograms, given the considerable variability. Future studies should consider the merits of very-broad spectrum prophylaxis and the potential role of molecular urinary pathogen (and pathogen-resistance) testing when selecting an optimal regimen.