Doses Of Ampicillin Research Articles

A retrospective cohort analysis of factors influencing continuous antibiotic therapy with ampicillin

AimsThere are limited data on ampicillin/sulbactam, both for continuous infusion and for use in critically ill patients. We aimed to identify factors that help predict ampicillin plasma levels during continuous antibiotic therapy in intensive care patients. Main methodsWe retrospectively reviewed and retrieved a large dataset of patients who received continuous ampicillin infusion with therapeutic drug monitoring between 2015 and 2022. Patients initially received standard dosing (single shot of 2/1 g followed by continuous infusion of 6/3 g ampicillin/sulbactam per day), which was then adjusted based on the results of regular therapeutic drug monitoring and according to a target range of 30–60 mg/l (equivalent to four to eight times the minimum inhibitory concentration of ampicillin for Enterobacterales). Main results466 measurements from 225 patients (152 male, mean age 61 years) were analyzed. Initial measurements of ampicillin plasma levels were below the predefined optimal therapeutic range in 50 %, within the range in 30 % and above the range in 20 %. Target attainment increased to 70 % by the 4th measurement. There was a significant negative correlation between ampicillin plasma levels and estimated glomerular filtration rate (eGFR) (r = −0.74; p < 0.001) and, to a lesser extent, with height (r = −0.31; p < 0.001). Based on multiple linear regression, eGFR and body weight or height were the factors accounting for 63 % of the variability in the data. SignificanceTo optimise target achievement, ampicillin dosing in critically ill patients requires a personalized approach based on renal function. Importantly, patients with normal or augmented eGFR require higher standard doses of ampicillin/sulbactam.

Escherichia coli persisters in biofilm can perform horizontal gene transfer by transformation

Persisters represent a subset of cells that exhibit transient tolerance to antimicrobials. These persisters can withstand sudden exposure to antimicrobials, even as the majority of normal cells perish. In this study, we have demonstrated the capacity of ampicillin-tolerant and alkali-tolerant persisters to execute horizontal gene transfer via in situ transformation within biofilms. Air–solid biofilms, comprising two Escherichia coli populations each with a distinct plasmid, were formed on agar media. They were treated with lethal doses of ampicillin or NaOH for 24 h, followed by a 1-min glass-ball roll. This process led to a high frequency of horizontal plasmid transfer (10−7–10−6 per cell) from dead cells to surviving persisters within the biofilms. Plasmid transfer was DNase-sensitive and also occurred by adding purified plasmid DNA to plasmid-free biofilms, demonstrating a transformation mechanism. This marks the first evidence of persisters’ novel ability for horizontal gene transfer, via transformation.

A 48-year-old man with fever, nauseous, vomiting, and dizzy: A CARE case report.

Listeria monocytogenes (LM) is an important foodborne bacterium, and LM meningoencephalitis is rare in clinical practice, with poor prognosis in severe patients. It is prone to misdiagnosis in clinical practice. We first reported a case of severe LM meningoencephalitis with muscle lesions and evaluated the comprehensive condition. A 48-year-old man had a fever and was admitted to the neurology department due to dizziness, nausea, and vomiting for 20 days. LM meningoencephalitis complicated with muscle lesions. We used moxifloxacin 0.4 g, qd, meropenem 2 g, q8h, and dexamethasone 10 mg, qd to reduce exudation and adhesion. Then due to consideration of side effects, we increased the dose of ampicillin by 2 g, q4h, stopped using meropenem and moxifloxacin, and turned to maintenance treatment with dexamethasone and ampicillin. We comprehensively managed his vital signs and physical organ functions, we also controlled some comorbidities. During the hospitalization period thereafter, we used intravenous anti-infection treatment with moxifloxacin 0.4 g, qd, ampicillin 0.5 g, q4h. Half a year later, the reexamination showed only protein elevation in cerebrospinal fluid and hydrocephalus in MRI. Afterward, the symptoms did not recur again. The patient recovered well after discharge. LM meningoencephalitis complicated with lower limb muscle lesions is clinically rare. This report focuses on relevant treatment plans, which provide value for the examination and comprehensive management of patients with LM infection in the future.

Synthesis and Characterization of Gold Nanoparticles (AuNPs) from Chrozophora rottleri (Geiseler) Spreng. An Evaluation of Antioxidant and Antimicrobial Activities

This is the first report of its kind on the study. Applications for nanobiotechnology include coatings, cosmetics, packaging, biomedicine, and boosting biological activity. Given the importance of Chrozophora rottleri (Euphorbiaceae) we developed gold nanoparticles (AuNPs) economically and ecologically responsibly. In less than a minute, the color of the gold nanoparticles (AuNPs) synthesized in this work changed from yellow to wine red. Advanced methods such as UV-visible spectroscopy, Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and zeta potential (ZP) were used to study these nanoparticles. The synthesized gold nanoparticles’ anti-microbial (bacterial and fungal) and in vitro antioxidant (DPPH and H2O2) characteristics were evaluated. Standard ascorbic acid concentrations of 10, 25, 50, 75, and 100 µg/ml were used to investigate the DPPH free radical scavenging activity. The findings showed that 18.53±0.162 was the lowest percentage of inhibition and 83.62±0.785 was the greatest. Analogously, the ascorbic acid hydrogen peroxide radical scavenging (H2O2) assay revealed that the maximum % inhibition was 87.27±0.467 and the lowest was 19.52±0.225. The Agar well-diffusion method was used to examine the antibacterial effectiveness of ampicillin and synthesized gold nanoparticles (AuNPs). Four distinct concentrations (25, 50, 75, and 100 µl) were assessed in relation to several bacterial pathogens, such as Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. Elevated doses of traditional Ampicillin demonstrated a progressive degree of inhibitory impact on E. coli and S. aureus, signifying heightened antimicrobial efficacy. Zones measuring 16 mm, 20 mm, 22 mm, and 25 mm were seen in ampicillin, while zones measuring 11 mm, 13 mm, 14 mm, and 16 mm were seen in E. coli The synthesized gold nanoparticles (CR-AuNPs) demonstrated increased zones of inhibition measuring 1.2 mm, 12 mm, 14 mm, and 17 mm, indicating greater antibacterial activity against S. pneumoniae. Similar to this, P. aeruginosa was inhibited by AuNPs, and the zones of inhibition measured 0.6 mm, 12 mm, 16 mm, and 18 mm. The CR-AuNPs show activity against S. aureus, E. coli, S. pneumoniae, and P. aeruginosa at a concentration of 200 µg/ml, which is the minimum inhibitory concentration (5, 10, 25, 50, 100, and 200 µg/ml). The well diffusion method was utilized to evaluate the antifungal efficacy of AuNPs and Fluconazole against Aspergillus niger. The findings showed that the zones of inhibition, which measured 12 mm, 16 mm, 21 mm, and 25 mm, gradually increased. Moreover, the zones of inhibition against Candida albicans were observed to be 13 mm, 16 mm, 18 mm, and 22 mm. At 12 mm, 15 mm, 19 mm, and 23 mm, the CR-AuNPs showed increasingly wider zones of inhibition against Aspergillus niger. Furthermore, 11 mm, 14 mm, 17 mm, and 19 mm zones of inhibition were seen in Candida albicans. The findings point to the potential for producing gold nanoparticles (AuNPs) using green synthesis methods that are both economical and ecologically benign. Moreover, this work is the first to suggest that C. rottleri may have antioxidant and antibacterial properties. As a result, this creates new chances in various fields in addition to medicines

Impact of Environmental Sub-Inhibitory Concentrations of Antibiotics, Heavy Metals, and Biocides on the Emergence of Tolerance and Effects on the Mutant Selection Window in E. coli.

Bacteria's ability to withstand the detrimental effects of antimicrobials could occur as resistance or tolerance with the minimum inhibitory concentration, the mutant prevention concentration, and the mutant selection window as salient concepts. Thus, this study assessed the impact of exposure to extremely high doses of ampicillin on the level of persistence and tolerance development in isolates previously exposed to different concentrations of selected antibiotics, biocides, and heavy metals. These isolates were previously exposed to oxytetracycline (OXYTET), amoxicillin (AMX), copper (Cu), zinc (Zn), benzalkonium chloride (BAC) 10, dimethylammonium chloride (DADMAC) 12 and a combination of all the individual pollutants (ALL). The isolates were exposed to very high concentrations (25 × MIC) of ampicillin, and their tolerance was calculated as the time required to kill 99.9% of the bacterial population (MDK99.9). The MDK99.9 increased by 30 to 50% in test isolates (DADMAC, OXYTET, Zinc = 28 h; BAC, Copper = 30 h; amoxycillin, ALL = 26 h) compared to the untreated control. BAC-exposed isolates decreased from 2.5 × 108 CFU/mL to 2.5 × 104 CFU/mL on the second day, displaying the highest tolerance increase. The tolerance appeared to originate from two sources, i.e., stochastic persistence and genetic-induced persistence, involving multiple genes with diverse mechanisms. The mutant selection window of the isolates to ampicillin, amoxicillin, and oxytetracycline also slightly increased compared to the control, indicating the selective survival of persister cells during the 30-day exposure. These findings indicate that bacterial exposure to sub-inhibitory concentrations of environmental chemical stressors may not always result in the development of antimicrobial resistance but could initiate this process by selecting persisters that could evolve into resistant isolates.

565. Pilot Study of Prolonged Post-Discontinuation Antibiotic Exposure (PDAE) to Ampicillin Among Low Birthweight Preterm Infants

Abstract Background In the United States, 75% of preterm infants receive ampicillin after birth for evaluation of early onset sepsis. Excess antibiotic exposure in preterm infants is associated with morbidity and mortality. Pharmacokinetic (PK) simulations suggest that very low birthweight (&amp;lt; 1500g) infants receiving ampicillin may experience excess and prolonged therapeutic exposures to ampicillin after drug discontinuation, called post-discontinuation antibiotic exposures (PDAE). It is unknown if low birthweight ( &amp;gt; 1500g to &amp;lt; 2500g) infants that receive ampicillin experience prolonged PDAE. Methods We conducted a pilot prospective PK clinical trial at a single tertiary care center. We enrolled infants with gestational age (GA) &amp;lt; 36 weeks and birthweight (BW) &amp;gt; 1500g and &amp;lt; 2500g who received ampicillin 200 mg/kg/day per standard of care. All infants received 6 ampicillin 66mg/kg doses administered Q8H within 24 hours following birth. Post-discontinuation PK samples were collected between 8-120 hours after the last dose of ampicillin. We performed descriptive statistics on patient characteristics, and graphically displayed ampicillin plasma concentrations following discontinuation. We defined therapeutic exposures as concentrations above the minimum inhibitory concentration (MIC) for Group B Streptococcus (0.25mcg/mL). Results We analyzed 20 PK samples from 12 infants with median (IQR) GA of 32 weeks (31, 34) and BW of 1838g (1730, 2060). See Table 1 for clinical characteristics. All infants (N=8) with post-discontinuation samples collected within 48 hours of last dose had continued therapeutic ampicillin exposures, only 25% of infants had continued therapeutic exposures between 48 and 72 hours post last dose (N=4), and none had therapeutic ampicillin exposures beyond 72 hours post-dose (Figure 1). Samples (n=5) within 24 hours of last dose had median (IQR) ampicillin concentration of 13.2mcg/mL (9.2, 18.7); those within 25-48 hours (n=3) had median concentration of 0.9 mcg/mL (0.6, 2.2). TABLE 1.Enrolled Patient Characteristics and Plasma Ampicillin ConcentrationsFigure 1.Ampicillin Post-Discontinuation Antibiotic Exposures in Low Birthweight Infants (1500g-2500g)MIC = minimum inhibitory concentration. GBS = Group B Streptococcus. Each individual symbol represents one sample collected. MICs based on European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (8 for E. coli, 0.25mcg/mL for Group B Streptococcus). Conclusion In this small cohort of premature infants, exposures of ampicillin remained therapeutic for at least 24 hours post drug discontinuation and suggests that shorter duration of empirical ampicillin treatments may be warranted in this population. Disclosures Daniel Benjamin, Jr., MD PhD MPH, Allergan: Advisor/Consultant|Melinta Therapuetics: Advisor/Consultant|Syneos Health: Advisor/Consultant Rachel Greenberg, MD, MB, MHS, Provepharm Inc: Advisor/Consultant|Tellus Therapeutics: Advisor/Consultant.

Foetal and neonatal exposure prediction and dosing evaluation for ampicillin using a physiologically-based pharmacokinetic modelling approach.

Ampicillin is frequently used in neonates for the treatment of sepsis and as an intrapartum prophylaxis option for Group B Streptococcus. Pharmacokinetic data to guide ampicillin dosing in neonates and during the intrapartum period are limited. The objective of this study was to build a physiologically-based pharmacokinetic (PBPK) model to characterize the disposition of ampicillin in neonates and foetuses and to inform corresponding optimal dosing regimens. An adult ampicillin PBPK model was first developed using the Simcyp® simulator. The adult model was then scaled to neonates by accounting for maturational changes in physiological parameters and age-dependent drug disposition or extended to a pregnancy model for mothers and foetuses. Models were verified using collected mean or individual-level concentration data from the literature. The developed adult PBPK model included elimination via glomerular filtration, OAT3-mediated tubular secretion and biliary excretion as well as hepatic metabolism, and 89.8% of the observed mean concentrations in adults were within a 2-fold range of model mean predictions. Most of the observed individual-level observations in neonates (78.4%) and foetuses (about 65% in two studies) were within the 90% prediction intervals. The recommended 50 mg/kg every 8 h (q8h) ampicillin regimen achieved the 75% fraction time of total drug concentration above minimum inhibitory concentration (T > MIC) target for an MIC ≤8mg/L in >90% virtual neonates, and 1g ampicillin for pregnant women provided adequate foetal exposure (>0.25 mg/L) for 4h prior to delivery. A PBPK model was developed to characterize ampicillin's disposition in neonates, pregnant women, and foetuses, and the model supported optimal dosing evaluation in these vulnerable populations.

Evaluation of the combined effect of antibiotics and essential oils against Campylobacter multidrug resistant strains and their biofilm formation

Introduction Campylobacter species are the first zoonotic pathogenic agents that are transmitted essentially to human via the consumption of contaminated food from animal origin. Aims The aim of the current work was to evaluate the Origanum compactum Benth, Rosmarinus officinalis L., Mentha pulegium L., and Lavandula stoechas L., essential oils antibacterial activity against 11 multidrug resistant strains of Campylobacter spp., study the synergistic effect of two essential oils in combination with two antibiotics and examine the capability of Campylobacter strains to produce biofilm. Material and methods The antibacterial activity of the four tested essential oils was evaluated using agar well diffusion and micro-dilution broth methods. These strains were also subjected to detection of biofilm and combinatory assay of essential oils and antibiotics using crystal violet and broth micro-dilution techniques respectively. Results The results showed that Campylobacter multidrug resistant strains were highly sensitive to O. compactum, M. pulegium and L. stoechas essential oils, in which the smallest MIC value noticed was 0.063% (v/v). The examined microorganisms formed moderate to strong biofilm biomass at 42 °C under aerobic conditions in nutriment broth and the pellicles formation was also observed in microaerobic environment. Our findings allow us to suggest that the main pure bioactive chemotypes of O..compactum, M. pulegium and L. stoechas essential oils may have an impressive inhibitory impact on Campylobacter strains that produce biofilm. To the best of our knowledge, this is the first in vitro report about combinatory effect of essential oils and antibiotics against Campylobacter spp. A high synergism was achieved with L. stoechas and O. compactum in combination with tetracycline or ampicillin, in which effective doses of EOs, ampicillin and tetracycline were reduced. No antagonistic effect was noticed in the strains tested. Nonetheless, the isolation of the main bioactive compounds of L. stoechas and M. pulegium need to be assessed, ex-vivo and in vivo, in order to fully elucidate the mechanism of action of these antimicrobial particles. Conclusion O. compactum and L. stoechas essential oils can be used alone or in mixtures to control Campylobacter spp. in food industries, farms, human and veterinary medicine.

Current Epidemiologic Status and Public Health Importance of Listeriosis: A Review

Listeriosis is a bacterial disease caused by different listeria species, among which Listeria monocytogenes are the most pathogenic species of ruminant animals and humans. This paper aimed to review current updates on the epidemiology and public health significance of listeriosis. The disease is an acute central nervous system infection, with associated abortions occurring in pregnant cattle. Reservoirs of infection are the soil and the intestinal tracts of asymptomatic animals, including wild and feral mammals, birds, and fish. Listeria, like other infections, occurs through ingestion as well as inhalation or direct contact and venereal transmission. In animals, listeriosis typically occurs after the consumption of contaminated silage or other feed sources. Consequently, contaminated food sources, such as raw meat and fish, unpasteurized dairy products, and uncooked vegetables, are good sources of infection in humans. The major clinical forms of listeriosis in cattle are encephalitis, abortion, Mastitis, iritis, The major clinical forms of listeriosis in cattle are encephalitis, abortion, mastitis, ophthalmitis, and keratoconjunctivitis ophthalmitis, iritis and keratoconjunctivitis. The disease can be tentatively diagnosed based on clinical symptoms, and its confirmation is achieved through serological tests and blood culture. Listeriosis shares similar clinical signs with other diseases, such as rabies, Coenurosis, and Scrapie. Response to antibiotic therapy may be poor in neural listeriosis. Prolonged high doses of ampicillin or amoxicillin combined with aminoglycosides may effectively prevent listeriosis in animals. Generally, disease prevention heavily depends on the protection of animal feed and vaccination. Moreover, humans are recommended to avoid eating and drinking uncooked meat and unpasteurized milk products.

A Proof of Concept of the Usefulness of a TDM-Guided Strategy for Optimizing Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Ampicillin-Based Regimens in a Case Series of Patients with Enterococcal Bloodstream Infections and/or Endocarditis.

(1) Objective: To describe the usefulness of a real-time therapeutic drug monitoring (TDM)-based strategy for optimizing pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion (CI) ampicillin-based regimens in a case series of patients affected by suspected or documented enterococcal bloodstream infections (BSIs) and/or infective endocarditis (IE). (2) Methods: Patients treated with CI ampicillin-based regimens for documented or suspected enterococcal BSI/IE who underwent real-time therapeutic drug monitoring (TDM)-based expert clinical pharmacological advice (ECPA) between June 2021 and May 2022 were retrospectively assessed. Ampicillin concentrations were determined at steady state, and the free fraction (fCss) was calculated according to a plasma protein binding of 20%. The fCss/MIC ratio was selected as the PD parameter for ampicillin efficacy and was defined as optimal for values between 4 and 8. The requirement for TDM-guided ampicillin dosing adjustments was assessed. (3) Results: Data for 12 patients with documented (n = 10) or suspected (n = 2) enterococcal infections (7 with BSIs and 5 with IE) were retrieved. The ampicillin PK/PD target was optimal over time in all of the 10 documented infections. None of the enterococcal BSIs persisted. Following the first real-time TDM-based ECPA, ampicillin dosage was decreased by >50% in 11 out of 12 patients (91.7%). (4) Conclusions: CI may be helpful in attaining aggressive ampicillin PK/PD targets in patients affected by enterococcal BSIs and/or IE. Administration of CI ampicillin after loading coupled with real-time TDM-based ECPA could be a valuable strategy for managing enterococcal infections.

An Uncommon Cause for Respiratory Failure in a Preterm Neonate.

An Uncommon Cause for Respiratory Failure in a Preterm Neonate.

Ampicillin dosing in premature infants for early-onset sepsis: exposure-driven efficacy, safety, and stewardship.

Objective:Define optimal ampicillin dosing for empiric early-onset sepsis (EOS) therapy in preterm neonates.Study design:We simulated ampicillin concentrations in newborns (birthweight<1500g; gestational age 22–27 weeks), summarizing three 48-hour regimens: high 100mg/kg Q8hr, medium 100mg/kg Q12hr, and standard 50mg/kg Q12hr. Concentration data were analyzed for concentration above minimum inhibitory concentration (MIC), below neurotoxicity threshold (Cmax≤140mcg/mL), and duration limited to 48 hours.Results:Among 34,689 newborns, all dosing regimens provided concentrations above MIC through 48 hours, but Cmax exceeded the neurotoxicity threshold. With the 4-dose standard regimen, >90% maintained concentrations >MIC beyond 48 hours. With the 2-dose regimen, newborns maintained the mean concentration >MIC within the 48-hour culture window and below neurotoxicity level. Infants 22–24 weeks’ gestation had higher drug concentrations and more prolonged exposure duration than 25–27 weeks’ gestation.Conclusions:For EOS in preterm infants, two ampicillin doses (50mg/kg) provided optimal bactericidal exposures, while minimizing potential toxicity.

Variation in ampicillin dosing for lower respiratory tract infections and neonatal bacterial infections in US children's hospitals.

We examined ampicillin dosing in pediatric patients across 3 conditions: (1) bacterial lower respiratory tract infections (LRTIs) in infants and children >3 months, (2) neonates with suspected or proven sepsis, and (3) neonates with suspected central nervous system (CNS) infections. We compared our findings to dosing guidance for these specific indications. Retrospective cohort study. The study included data from 32 children's hospitals in the United States. We reviewed prescriptions from the SHARPS study of antimicrobials, a survey of antibiotic prescribing from July 2016 to December 2017. Prescriptions were analyzed for indication, total daily dose per kilogram, and presence of antimicrobial stewardship program (ASP) review. LRTI prescriptions were compared to IDSA recommendations for community-acquired pneumonia. Neonatal prescriptions were compared to recommendations from the American Academy of Pediatrics (AAP). Prescriptions were categorized as "optimal" (80%-120% of recommended dosing), "suboptimal" (<80% of recommended dosing), or "excessive" (>120% of recommended dosing). Among 1,038 ampicillin prescriptions, we analyzed 88 prescriptions for LRTI, 499 prescriptions for neonatal sepsis, and 27 prescriptions for neonatal CNS infection. Of the LRTI prescriptions, 77.3%were optimal. Of prescriptions for neonatal sepsis, 81.6% were excessive compared to AAP bacteremia recommendations but 78.8% were suboptimal compared to AAP meningitis guidelines. Also, 48.1% of prescriptions for neonatal CNS infection were suboptimal, and 50.6% of prescriptions were not reviewed by the ASP. LRTI dosing is generally within the IDSA-recommended range. However, dosing for neonatal sepsis often exceeds the recommendation for bacteremia but is below the recommendation for meningitis. This variability points to an important opportunity for future antimicrobial stewardship efforts.

Ampicillin Pharmacokinetics in Peripartum and Laboring Women.

Ampicillin is used for multiple peripartum indications including prevention of neonatal group B streptococcus (GBS) and treatment of chorioamnionitis. Despite its widespread use in obstetrics, existing pharmacokinetic data for ampicillin do not address contemporary indications or dosing paradigms for this population. We sought to characterize the pharmacokinetic profile of ampicillin administered to laboring women. Using whole blood dried blood spot sampling technique, maternal blood samples were collected at specified times from 31 women receiving intravenous (IV) ampicillin for peripartum indications. Women received either a 2-g loading dose with 1-g administered every 4 hours (GBS) or 2-g every 6 hours (chorioamnionitis). Pharmacokinetics were analyzed via a population approach with nonlinear mixed-effect modeling. The data were best described by a two-compartment model with first-order elimination, with the following whole blood parameters: central volume of distribution (V1), 75.2 L (95% confidence interval [CI]: 56.3-93.6); clearance (CL), 82.4 L/h (95% CI: 59.7-95.7); intercompartmental clearance (Q), 20.9 L/h (95% CI: 16.2-38.2); and peripheral volume of distribution (V2), 61.1 L (95% CI: 26.1-310.5). Interpatient variation in CL and V1 was large (42.0 and 56.7%, respectively). Simulations of standard dosing strategies demonstrated over 98% of women are predicted to achieve an estimated free plasma concentration above mean inhibitory concentration (MIC) of 0.5 μg/mL for more than 50% of the dosing interval. Although large variation in the pharmacokinetics of ampicillin in pregnant women exists, as predicted by our model, current standard dosing strategies achieve adequate exposure for GBS in nearly all patients. · IV ampicillin is widely used in obstetrics.. · Pharmacokinetic studies are lacking.. · Ampicillin pharmacokinetics were established.. · Ampicillin clearance and volume of distribution are high.. · Current ampicillin dosing strategies are sufficient..

Antibiofilm Effects of Epigallocatechin Gallate Against Proteus mirabilis Wild-Type and Ampicillin-Induced Strains.

Proteus mirabilis is an opportunistic pathogen associated with nosocomial infections and foodborne diseases. The resistance and biofilm formation of P. mirabilis have been a great concern. In this study a multidrug-resistant P. mirabilis strain 012 was exposed to a lethal dose of ampicillin (10 mg/mL, 2.5-fold minimal bactericidal concentration) for 24 h at 37°C. After resuscitation and isolation, five variant isolates were selected and subjected to ampicillin induction by repeatedly streaking on ampicillin-containing plates (10 mg/mL) for at least three times. In biofilm formation assays by using crystal violet staining, we found that the variant strains had enhanced biofilm-forming abilities. (-)-epigallocatechin-3-gallate (EGCG) at a minimum inhibitory concentration (MIC) (256 μg/mL) significantly reduced the biofilm formation of all variant strains and the wild-type strain (p < 0.01). Sub-MIC of EGCG (128 μg/mL) suppressed the biofilms of wild-type and two variants. However, it stimulated the biofilms of the other three variants. The antibiofilm effects of EGCG against the wild-type strain were further confirmed by confocal laser scanning microscopy. Scanning electron microscopy revealed that EGCG induced variants to form more fibrous structures. Our results revealed that a lethal dose of antibiotic exposure increased antibiotic resistance and biofilm formation of P. mirabilis. EGCG may be used as a promising antibiofilm agent to prevent the P. mirabilis biofilm formation in the food industry. However, the sub-MIC of EGCG is not effective and will not be applied.

Hyponatremia, Metabolic Acidosis, and Abnormal Newborn Screen in a Preterm Neonate.

A 2,250-g male neonate is born at 34 weeks of gestation via spontaneous vaginal delivery to a 30-year-old gravida 1, para 0 woman after presentation to a community hospital with uterine contractions and spontaneous rupture of membranes. The mother receives 1 dose of ampicillin, 1 dose of betamethasone, and magnesium before delivery. At delivery, the neonate is vigorous and crying. His Apgar scores are 8 and 9 at 1 and 5 minutes after birth, respectively, with no abnormalities noted on physical examination. In the first couple of hours after birth, he develops persistent oxygen desaturations and is started on continuous positive airway pressure.He is admitted to the NICU for prematurity and low birthweight. Admission examination demonstrates nondysmorphic features, no respiratory distress with good air exchange, regular heart rate and rhythm without murmur, soft and flat abdomen, patent anus, normal external male genitalia, unremarkable neurologic findings, and pink skin color.Chest radiography shows mild diffuse ground-glass reticular densities. He is placed on a stock solution of parenteral nutrition via a peripheral intravenous catheter. Antibiotics are started because of the mother’s unknown group B Streptococcus status and preterm labor. Initial surveillance of electrolytes demonstrates sodium, potassium, calcium, phosphorus, and glucose levels within normal limits. On day 4 after birth, the neonate continues on nasal canula for tachypnea, receiving parenteral nutrition, and advancing gavage feeds of maternal breast milk or formula. A capillary blood gas measurement shows mild metabolic acidosis, with a pH of 7.28, Pco2 32 mm Hg (4.26 kPa), and bicarbonate 19 mEq/L (19 mmol/L).On day 6 after birth, repeat surveillance of electrolytes shows a sodium concentration of 126 mEq/L (126 mmol/L) and potassium of 6.7 mEq/L (6.7 mmol/L). Glucose concentration is 53 mg/dL (2.94 mmol/L). Blood gas continues to show mild metabolic acidosis with a pH of 7.27, Pco2 31 mm Hg (4.12 kPa), and bicarbonate 19 mEq/L (19 mmol/L). Results of the state newborn screening demonstrate an elevated 17-hydroxyprogesterone (17-OHP) of 221 nmol/L (normal <80 nmol/L) on dried blood spot testing, or 14,586 ng/dL (normal <5,280 ng/dL) as serum equivalent. A confirmatory serum 17-OHP level is sent that same day. The pediatric endocrinology service is consulted for the concerning laboratory results.The neonate is transferred to a tertiary care pediatric hospital for further management. He is started on hydrocortisone and fludrocortisone replacements along with sodium chloride supplementation. Repeat serum 17-OHP before treatment is greater than 50,000 ng/dL, and the actual diagnosis of classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is made.The neonate continues to appear well with normal vital signs, including blood pressure. He is breathing room air, receiving full enteral feeds, and working on oral feeds with the occupational therapist. Parenteral nutrition has been discontinued.The differential diagnosis for hyponatremia and hyperkalemia in a neonate includes CAH, pseudohypoaldosteronism, inappropriate parenteral nutrition composition, and exogenous diuretic use.CAH is a group of autosomal recessive disorders encompassing enzyme deficiencies in the adrenal steroidogenesis pathway and is the most common cause of primary adrenal insufficiency in children. The classic form of CAH affects 1 in 15,000 neonates and is commonly identified through newborn screening, (1) with screening mandated across the United States since 2008. (2) Most cases of CAH are caused by 21-OHD, which is marked by an elevated serum 17-OHP. In the steroidogenic pathway, 17-OHP is the precursor in the enzymatic reaction that is catalyzed by 21-OHD, and is the primary analyte tested in newborn screening for CAH. If treatment is not initiated early, neonates may present in acute salt-wasting adrenal crisis with vomiting, hypotension, and severe dehydration, electrolyte abnormalities, and hypoglycemia. (1)(3)(4)(5) Female neonates with classic CAH also present with virilization of external genitalia at birth.False-positive newborn screening results for CAH are common in preterm neonates, related to the fact that healthy preterm neonates have higher overall levels of 17-OHP compared with term neonates. (6) Thus, many screening programs have established reference ranges that are based on weight and gestational age.For neonates with classic CAH, therapy should be initiated soon after birth to reduce the potentially life-threatening sequelae of CAH. Classic CAH is treated with steroid hormone replacements including hydrocortisone (to replace cortisol) and fludrocortisone (to replace aldosterone). Supplemental sodium chloride (salt) is also recommended for neonates with classic CAH who could have salt-wasting.

Antimicrobially Active Semen Extenders Allow the Reduction of Antibiotic Use in Pig Insemination

Antibiotic use in semen extenders for livestock may contribute to the development and spreading of multi-drug resistance. Antimicrobial control in semen doses for artificial insemination of pigs is indispensable due to the relatively high storage temperature (17 °C). The objectives of this study were first, to examine whether the antimicrobial capacity differs between antibiotic-free extenders and second, to determine whether an antimicrobial active extender provides the possibility to reduce antibiotics. Antibiotic-free semen extenders Beltsville Thawing Solution (BTS) and Androstar Premium were inoculated at 103 to 104 CFU/mL with four pure bacterial strains isolated from boar ejaculates or a mixture thereof, and then stored for 144 h at 17 °C. Bacterial counts after aerobic culture decreased in BTS up to one log level and decreased in Androstar Premium by 2 to 3.5 log levels (p < 0.05). In semen samples from nine boars stored in the inoculated Androstar Premium extender containing half of the standard concentration of gentamicin, bacteria counts were below 101 CFU/mL. Likewise, half of the standard dose of apramycin and ampicillin was fully antimicrobially active and sperm quality was maintained. In conclusion, semen extenders with intrinsic antimicrobial activity allow a reduction in antibiotic use in pig insemination.

Insights into nitrogen removal from seawater-based wastewater through marine anammox bacteria under ampicillin stress: Microbial community evolution and genetic response

Global spread of ampicillin (AMP) in the aquatic environment have attracted much attention recently. Marine anammox bacteria (MAB) have potentials in saline wastewater treatment due to their good salt tolerance. However, to date, the effect resulting from AMP on MAB is still unknown. Herein, the effect of AMP on MAB, involving microbial community evolution and genetic response, was investigated for the first time. A lab-scale reactor inoculated by MAB sludge was operated under saline condition (35 g/L) and AMP stress of different gradients. Within 200 cycles, nitrogen removal performance was monitored and sludge samples were withdrawn for high-throughput sequencing analyses and qPCR. The results confirmed that the nitrogen removal capacity of MAB declined with increasing AMP dosage, and almost collapsed at 300 mg/L AMP. The total nitrogen removal rate and specific anammox activity finally dropped to 0.17 kg N m−3 d−1 and 101.86 mg N g−1VSS d−1, respectively. Pseudoalteromonas (38.13%) dominated the reactor on Cycle 190, which formed a new symbiosis with MAB. And the emergence of oleophilic bacteria such as Colwellia (2.53%) was also observed. Moreover, antibiotic resistance genes were detected with increased abundance and diversity, indicating the AMP dosing significantly promoted microbial community evolution and genetic response.

Endothelial Dysfunction and Impaired Neurovascular Coupling Responses Precede Cognitive Impairment in a Mouse Model of Geriatric Sepsis.

Sepsis is a life-threatening condition, the incidence of which is significantly increased in elderly patients. One of the long-lasting effects of sepsis is cognitive impairment defined as a new deficit or exacerbation of preexisting deficits in global cognition or executive function. Normal brain function is dependent on moment-to-moment adjustment of cerebral blood flow to match the increased demands of active brain regions. This homeostatic mechanism, termed neurovascular coupling (NVC, also known as functional hyperemia), is critically dependent on the production of vasodilator NO by microvascular endothelial cells in response to mediators released from activated astrocytes. The goal of this study was to test the hypothesis that sepsis in aging leads to impairment of NVC responses early after treatment and that this neurovascular dysfunction associates with impairments in cognitive performance and vascular endothelial dysfunction. To test this hypothesis, we used a commonly studied bacterial pathogen, Listeria monocytogenes, to induce sepsis in experimental animals (males, 24 months of age) and subjected experimental animals to a standard clinical protocol of 3 doses of ampicillin i.p. and 14 days of amoxicillin added to the drinking water. NVC responses, endothelial function and cognitive performance were measured in septic and age-matched control groups within 14 days after the final antibiotic treatment. Our data demonstrate that sepsis in aging significantly impairs NVC responses measured in somatosensory cortex during whisker stimulation, significantly impairs endothelial function in isolated and pressure cannulated aorta rings in response to acetylcholine stimulation. No significant impairment of cognitive function in post-sepsis aged animals has been observed when measured using the PhenoTyper homecage based system. Our findings suggest that sepsis-associated endothelial dysfunction and impairment of NVC responses may contribute to long-term cognitive deficits in older sepsis survivors.

Ampicillin Pharmacokinetics During First Week of Life in Preterm and Term Neonates

Ampicillin is 1 of the most commonly used antibiotics for treatment of early onset sepsis, but its pharmacokinetics (PK) is poorly characterized. We aimed to define the dose of ampicillin for late preterm and term neonates by evaluating its PK in serum, cerebrospinal (CSF), and epithelial lining fluid. A prospective study included neonates receiving ampicillin for suspected or proven early onset sepsis and pneumonia. PK samples were collected at steady state, at predose and 5 minutes, 1 hour, 3 hours, 8 hours, and 12 hours after ampicillin 3-minute infusion. Ampicillin concentrations were measured by ultra-high-performance liquid chromatography. Noncompartmental anaysis (NCA) and population pharmacokinetic (pop-PK) modeling were performed and probability of therapeutic target attainment was simulated. In 14 neonates (GA of 32-42 wks; mean BW 2873 g), PK parameters (mean ± SD) in NCA were the following: half-life 7.21 ± 7.97 hours; volume of distribution (Vd) 1.07 ± 0.51 L; clearance (CL) 0.20 ± 0.13 L/h; 24-hour area under the concentration-time curve 348.92 ± 114.86 mg*h/L. In pop-PK analysis, a 2-compartmental model described the data most adequately with the final parameter estimates of CL 15.15 (CV 40.47%) L/h/70kg; central Vd 24.87 (CV 37.91%) L/70kg; intercompartmental CL 0.39 (CV 868.56) L/h and peripheral Vd 1.039 (CV 69.32%) L. Peutic target attainment simulations demonstrated that a dosage of 50 mg/kg q 12 hours attained 100% fT > MIC 0.25 mg/L, group B streptococcal breakpoint. We recommend ampicillin dosage 50 mg/kg q 12 hours for neonates with gestational age ≥32 weeks during the first week of life.