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Microbiology Spectrum Aug 2022Penicillin plus ceftriaxone is a promising alternative to ampicillin plus ceftriaxone for the treatment of Enterococcus faecalis infective endocarditis. Limited data is...
Penicillin plus ceftriaxone is a promising alternative to ampicillin plus ceftriaxone for the treatment of Enterococcus faecalis infective endocarditis. Limited data is available supporting the utilization of penicillin plus ceftriaxone. A total of 20 E. faecalis isolates; one wild-type strain (JH2-2) and 19 clinical blood strains were assessed for penicillin plus ceftriaxone and ampicillin plus ceftriaxone synergy using a 24-h time-kill experiment. Susceptibility was determined by broth microdilution. Differences in bactericidal, bacteriostatic, or inactivity, as well as synergy between treatments were assessed by chi-square or Fisher exact test. All E. faecalis isolates were considered susceptible to ampicillin and penicillin. Ampicillin plus ceftriaxone versus penicillin plus ceftriaxone similarly demonstrated synergy. Bactericidal activity was more commonly observed for ampicillin plus ceftriaxone versus penicillin plus ceftriaxone. Among isolates with a penicillin MIC of 4 μg/mL ( = 7), synergistic activity for both combinations was less common compared to isolates with a penicillin MIC ≤ 2 μg/mL ( = 13). Ampicillin plus ceftriaxone and penicillin plus ceftriaxone demonstrate similar synergistic potential against E. faecalis clinical blood isolates, but strains with higher penicillin and ceftriaxone MICs less frequently demonstrated synergy. Further research is warranted to determine the role of the penicillin plus ceftriaxone therapy and the penicillin MIC in clinical practice. Penicillin plus ceftriaxone demonstrates similar synergistic activity against to ampicillin plus ceftriaxone. Isolates with a penicillin MIC of 4 mg/L and a ceftriaxone MIC of 512 or higher, lack penicillin plus ceftriaxone synergy despite the penicillin susceptibility MIC breakpoint of 8 mg/L.
Topics: Ampicillin; Anti-Bacterial Agents; Ceftriaxone; Drug Synergism; Drug Therapy, Combination; Enterococcus faecalis; Microbial Sensitivity Tests; Penicillins
PubMed: 35703558
DOI: 10.1128/spectrum.00621-22 -
Scientific Reports Aug 2020Immediate hypersensitivity reaction (IHR) can be divided into allergic- and non-allergic-mediated, while "anaphylaxis" is reserved for severe IHR. Clinically, true...
Immediate hypersensitivity reaction (IHR) can be divided into allergic- and non-allergic-mediated, while "anaphylaxis" is reserved for severe IHR. Clinically, true penicillin allergy is rare and most reported penicillin allergy is "spurious". Penicillin-initiated anaphylaxis is possible to occur in skin test- and specific IgE-negative patients. The contact system is a plasma protease cascade initiated by activation of factor XII (FXII). Many agents with negative ion surface can activate FXII to drive contact system. Our data showed that penicillin significantly induced hypothermia in propranolol- or pertussis toxin-pretreated mice. It also caused a rapid and reversible drop in rat blood pressure, which did not overlap with IgE-mediated hypotension. These effects could be countered by a bradykinin-B2 receptor antagonist icatibant, and consistently, penicillin indeed increased rat plasma bradykinin. Moreover, penicillin not only directly activated contact system FXII-dependently, but also promoted bradykinin release in plasma incubated-human umbilical vein endothelial cells. In fact, besides penicillin, other beta-lactams also activated the contact system in vitro. Since the autoactivation of FXII can be affected by multiple-factors, plasma from different healthy individuals showed vastly different amidolytic activity in response to penicillin, suggesting the necessity of determining the potency of penicillin to induce individual plasma FXII activation. These results clarify that penicillin-initiated non-allergic anaphylaxis is attributed to contact system activation, which might bring more effective diagnosis options for predicting penicillin-induced fatal risk and avoiding costly and inappropriate treatment clinically.
Topics: Anaphylaxis; Animals; Blood Coagulation; Bradykinin; Bradykinin Receptor Antagonists; Capillary Permeability; Enzyme Activation; Factor XIIa; Human Umbilical Vein Endothelial Cells; Humans; Hypothermia; Kallikrein-Kinin System; Male; Mice; Mice, Inbred BALB C; Penicillin G; Pertussis Toxin; Propranolol; Rats; Rats, Sprague-Dawley; Receptor, Bradykinin B2; beta-Lactams
PubMed: 32843685
DOI: 10.1038/s41598-020-71083-x -
Journal of Microbiology and... Apr 2024is a commonly used probiotic, and many researchers have focused on its stress response to improve its functionality and survival. However, studies on persister cells,...
is a commonly used probiotic, and many researchers have focused on its stress response to improve its functionality and survival. However, studies on persister cells, dormant cells that aid bacteria in surviving general stress, have focused on pathogenic bacteria that cause infection, not . Thus, understanding persister cells will provide essential clues for understanding how survives and maintains its function under various environmental conditions. We treated strains with various antibiotics to determine the conditions required for persister formation using kill curves and transmission electron microscopy. In addition, we observed the resuscitation patterns of persister cells using single-cell analysis. Our results show that creates a small population of persister cells (0.0001-1% of the bacterial population) in response to beta-lactam antibiotics such as ampicillin and amoxicillin. Moreover, only around 0.5-1% of persister cells are heterogeneously resuscitated by adding fresh media; the characteristics are typical of persister cells. This study provides a method for forming and verifying the persistence of and demonstrates that antibiotic-induced persister cells show characteristics of dormancy, sensitivity of antibiotics, same as exponential cells, multi-drug tolerance, and resuscitation, which are characteristics of general persister cells. This study suggests that the mechanisms of formation and resuscitation may vary depending on the characteristics, such as the membrane structure of the bacterial species.
Topics: Anti-Bacterial Agents; Lactobacillus; Ampicillin; Microbial Viability; Microbial Sensitivity Tests; Microscopy, Electron, Transmission; Probiotics; Amoxicillin
PubMed: 38326923
DOI: 10.4014/jmb.2312.12035 -
International Journal of Environmental... Aug 2022Antibiotic residues lead to the risk of resistance gene enrichment, which is the main reason why penicillin mycelial dreg (PMD) is defined as hazardous waste....
Antibiotic residues lead to the risk of resistance gene enrichment, which is the main reason why penicillin mycelial dreg (PMD) is defined as hazardous waste. Hydrothermal treatment (HT) is an effective method to treat penicillin mycelial dreg, but the degradation mechanism of penicillin is unclear. In the study, we researched the effects of pH (4-10) at 80-100 °C and metal ions (Mn, Fe, Cu, and Zn) at several concentrations on the HT of penicillin, identified the degradation products (DPs) under different conditions, and evaluated the antibacterial activity of hydrothermally treated samples. The results show that penicillin degradation kinetics highly consistent with pseudo-first-order model (R = 0.9447-0.9999). The degradation rates () at pH = 4, 7, and 10 were 0.1603, 0.0039, and 0.0485 min, indicating acidic conditions were more conducive to penicillin degradation. Among the four tested metal ions, Zn had the most significant catalytic effect. Adding 5 mg·L Zn caused 100% degradation rate at pH = 7 after HT for 60 min. Six degradation products (DPs) with low mass-to-charge (/ ≤ 335) were detected under acidic condition. However, only two and three DPs were observed in the samples catalyzed by Zn and alkali, respectively, and penilloic acid (/ = 309) was the main DPs under these conditions. Furthermore, no antibacterial activity to was detected in the medium with up to 50% addition of the treated samples under acidic condition. Even though acid, alkali, and some metal ions can improve the degradation ability of penicillin, it was found that the most effective way for removing its anti-bacterial activity was under the acidic condition. Therefore, resistance residue indicates the amount of additive in the process of resource utilization, and avoids the enrichment of resistance genes.
Topics: Alkalies; Anti-Bacterial Agents; Hydrogen-Ion Concentration; Ions; Kinetics; Metals; Penicillins
PubMed: 36078417
DOI: 10.3390/ijerph191710701 -
Clinical Infectious Diseases : An... Nov 2023There is a lack of evidence on oral amoxicillin pharmacokinetics and exposure in neonates with possible serious bacterial infection (pSBI). We aimed to describe...
BACKGROUND
There is a lack of evidence on oral amoxicillin pharmacokinetics and exposure in neonates with possible serious bacterial infection (pSBI). We aimed to describe amoxicillin disposition following oral and intravenous administration and to provide dosing recommendations for preterm and term neonates treated for pSBI.
METHODS
In this pooled-population pharmacokinetic study, 3 datasets were combined for nonlinear mixed-effects modeling. In order to evaluate amoxicillin exposure following oral and intravenous administration, pharmacokinetic profiles for different dosing regimens were simulated with the developed population pharmacokinetic model. A target of 50% time of the free fraction above the minimal inhibitory concentration (MIC) with an MICECOFF of 8 mg/L (to cover gram-negative bacteria such as Escherichia coli) was used.
RESULTS
The cohort consisted of 261 (79 oral, 182 intravenous) neonates with a median (range) gestational age of 35.8 weeks (range, 24.9-42.4) and bodyweight of 2.6 kg (range, 0.5-5). A 1-compartment model with first-order absorption best described amoxicillin pharmacokinetics. Clearance (L/h/kg) in neonates born after 30 weeks' gestation increased with increasing postnatal age (PNA day 10, 1.25-fold; PNA day 20, 1.43-fold vs PNA day 3). Oral bioavailability was 87%. We found that a twice-daily regimen of 50 mg/kg/day is superior to a 3- or 4-times daily schedule in the first week of life for both oral and intravenous administration.
CONCLUSIONS
This pooled population pharmacokinetic description of intravenous and oral amoxicillin in neonates provides age-specific dosing recommendations. We conclude that neonates treated with oral amoxicillin in the first weeks of life reach adequate amoxicillin levels following a twice-daily dosing regimen. Oral amoxicillin therapy could therefore be an adequate, cost-effective, and more patient-friendly alternative for neonates worldwide.
Topics: Infant, Newborn; Humans; Infant; Amoxicillin; Gestational Age; Bacterial Infections; Infusions, Intravenous; Gram-Negative Bacteria; Anti-Bacterial Agents
PubMed: 37757471
DOI: 10.1093/cid/ciad432 -
JAMA Network Open May 2022There is a lack of studies comparing the intended and unintended consequences of prospective review and feedback (PRF) with computerized decision support systems (CDSS),...
IMPORTANCE
There is a lack of studies comparing the intended and unintended consequences of prospective review and feedback (PRF) with computerized decision support systems (CDSS), especially in the longer term in antimicrobial stewardship.
OBJECTIVE
To examine the outcomes associated with the sequential implementation of PRF and CDSS and changes to these interventions with long-term use of antibiotics for and incidence of multidrug resistant organisms (MDROs) and other unintended outcomes.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used an interrupted time series with segmented regression analysis of data from January 2007 to December 2018. Data were extracted from the electronic medical records of patients admitted at a large university teaching hospital with high rates of antibiotic resistance in Singapore. Data were analyzed from June 2019 to June 2020.
EXPOSURES
PRF of piperacillin-tazobactam and carbapenems (intervention 1, April 2009), with the addition of hospital-wide CDSS (intervention 2, April 2011), and lifting of CDSS for half of the hospital wards for 6 months (intervention 3, March 2017).
MAIN OUTCOMES AND MEASURES
Monthly antimicrobial use was measured in defined daily doses (DDDs) per 1000 patient-days. The monthly incidence of MDROs was calculated as number of clinical isolates detected per 1000 inpatient-days over a 6-month period. Unintended outcomes examined included in-hospital mortality and age-adjusted length of stay (LOS).
RESULTS
The number of inpatients increased from 56 263 in 2007 to 63 572 in 2018. During the same period, the mean monthly patient days increased from 33 929 in 2007 to 45 603 in 2018, and the proportion of patients older than 65 years increased from 45.5% in 2007 to 56.6% in 2018. After intervention 1, there were 0.33 (95% CI, 0.18 to 0.48) more DDDs per 1000 patient-days per month of piperacillin-tazobactam and carbapenems and -11.05 (95% CI, -15.55 to -6.55) fewer DDDs per 1000 patient-days per month for other broad-spectrum antibiotics. After intervention 2, there were -0.22 (95% CI, -0.33 to -0.10) fewer DDDs per 1000 patient-days per month of piperacillin-tazobactam and carbapenems and -2.10 (95% CI, -3.13 to -1.07) fewer DDDs per 1000 patient-days per month for other broad-spectrum antibiotics. After intervention 3, use of piperacillin-tazobactam and carbapenem increased by 0.28 (95% CI, 0.02 to 0.55) DDDs per 1000 patient-days per month. After intervention 2, incidence of Clostridioides difficile decreased (estimate, -0.02 [95% CI, -0.03 to -0.01] cases per 1000 patient-days per month).
CONCLUSIONS AND RELEVANCE
In this cohort study, concurrent PRF and CDSS were associated with limiting the use of piperacillin-tazobactam and carbapenems while reducing use of other antibiotics.
Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Carbapenems; Cohort Studies; Drug Resistance, Microbial; Humans; Piperacillin; Prospective Studies; Tazobactam
PubMed: 35503216
DOI: 10.1001/jamanetworkopen.2022.10180 -
The Journal of Infectious Diseases Jun 2022Historically, antimicrobial resistance has been rare in US invasive meningococcal disease cases.
BACKGROUND
Historically, antimicrobial resistance has been rare in US invasive meningococcal disease cases.
METHODS
Meningococcal isolates (n = 695) were collected through population-based surveillance, 2012-2016, and national surveillance, 2015-2016. Antimicrobial susceptibility was assessed by broth microdilution. Resistance mechanisms were characterized using whole-genome sequencing.
RESULTS
All isolates were susceptible to 6 antibiotics (cefotaxime, ceftriaxone, meropenem, rifampin, minocycline, and azithromycin). Approximately 25% were penicillin or ampicillin intermediate; among these, 79% contained mosaic penA gene mutations. Less than 1% of isolates were penicillin, ampicillin, ciprofloxacin, or levofloxacin resistant.
CONCLUSIONS
Penicillin- and ampicillin-intermediate isolates were common, but resistance to clinically relevant antibiotics remained rare.
Topics: Ampicillin; Anti-Bacterial Agents; Ceftriaxone; Ciprofloxacin; Humans; Meningococcal Infections; Microbial Sensitivity Tests; Neisseria meningitidis; Penicillins; United States
PubMed: 35266516
DOI: 10.1093/infdis/jiac046 -
Medicine Jul 2023The objective was to compare the clinical efficacy of cefoperazone-sulbactam with piperacillin-tazobactam in the treatment of severe community-acquired pneumonia (SCAP)....
The objective was to compare the clinical efficacy of cefoperazone-sulbactam with piperacillin-tazobactam in the treatment of severe community-acquired pneumonia (SCAP). The retrospective study was conducted from March 1, 2018 to May 30, 2019. Clinical outcomes were compared for patients who received either cefoperazone-sulbactam or piperacillin-tazobactam in the treatment of SCAP. A total of 815 SCAP patients were enrolled. Among them, 343 received cefoperazone-sulbactam, and 472 received piperacillin-tazobactam. Patients who received cefoperazone-sulbactam presented with higher Charlson Comorbidity Index scores. (6.20 ± 2.77 vs 5.72 ± 2.61; P = .009). The clinical cure rates and effectiveness for patients receiving cefoperazone-sulbactam and piperacillin-tazobactam were 84.2% versus 80.3% (P = .367) and 85.4% versus 83.3% (P = .258), respectively. In addition, the overall mortality rate of the cefoperazone-sulbactam group was 16% (n = 55), which was also comparable to the piperacillin-tazobactam group (17.8%, n = 84, P = .572). The primary clinical outcomes for patients receiving cefoperazone-sulbactam were superior compared to those receiving piperacillin-tazobactam after adjusting disease severity status. The clinical efficacy of cefoperazone-sulbactam in the treatment of adult patients with SCAP is comparable to that of piperacillin-tazobactam. After adjusting for disease severity, cefoperazone-sulbactam tended to be superior to piperacillin-tazobactam.
Topics: Humans; Cefoperazone; Sulbactam; Anti-Bacterial Agents; Piperacillin; Retrospective Studies; Penicillanic Acid; Piperacillin, Tazobactam Drug Combination; Treatment Outcome; Microbial Sensitivity Tests; Community-Acquired Infections; Pneumonia
PubMed: 37443505
DOI: 10.1097/MD.0000000000034284 -
Revista Espanola de Enfermedades... Sep 2019Helicobacter pylori eradication cures most peptic ulcers and non-atrophic chronic gastritis, and may potentially prevent over 70% of gastric cancers. In the late 1980s,...
Helicobacter pylori eradication cures most peptic ulcers and non-atrophic chronic gastritis, and may potentially prevent over 70% of gastric cancers. In the late 1980s, shortly after the discovery of H. pylori, eradication therapy was established based on the use of two antibiotics (amoxicillin and clarithromycin) and one proton-pump inhibitor for 7 or 10 days (OCA7, OCA10). This therapy, recommended during the first Maastricht Consensus Conference, obtained eradication rates above 90%, and was equally effective everywhere around the world. However, over time, H. pylori has developed resistance to several antibiotics.
Topics: Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Microbial; Helicobacter Infections; Helicobacter pylori; Humans; Proton Pump Inhibitors
PubMed: 31476871
DOI: 10.17235/reed.2019.6575/2019 -
BMC Infectious Diseases Sep 2023Many factors determine empirical antibiotic treatment of community-acquired pneumonia (CAP). We aimed to describe the empirical antibiotic treatment CAP patients with an...
Empirical antibiotic treatment for community-acquired pneumonia and accuracy for Legionella pneumophila, Mycoplasma pneumoniae, and Clamydophila pneumoniae: a descriptive cross-sectional study of adult patients in the emergency department.
BACKGROUND
Many factors determine empirical antibiotic treatment of community-acquired pneumonia (CAP). We aimed to describe the empirical antibiotic treatment CAP patients with an acute hospital visit and to determine if the current treatment algorithm provided specific and sufficient coverage against Legionella pneumophila, Mycoplasma pneumoniae, and Clamydophila pneumoniae (LMC).
METHODS
A descriptive cross-sectional, multicenter study of all adults with an acute hospital visit in the Region of Southern Denmark between January 2016 and March 2018 was performed. Using medical records, we retrospectively identified the empirical antibiotic treatment and the microbiological etiology for CAP patients. CAP patients who were prescribed antibiotics within 24 h of admission and with an identified bacterial pathogen were included. The prescribed empirical antibiotic treatment and its ability to provide specific and sufficient coverage against LMC pneumonia were determined.
RESULTS
Of the 19,133 patients diagnosed with CAP, 1590 (8.3%) patients were included in this study. Piperacillin-tazobactam and Beta-lactamase sensitive penicillins were the most commonly prescribed empirical treatments, 515 (32%) and 388 (24%), respectively. Our analysis showed that 42 (37%, 95% CI: 28-47%) of 113 patients with LMC pneumonia were prescribed antibiotics with LMC coverage, and 42 (12%, 95% CI: 8-15%) of 364 patients prescribed antibiotics with LMC coverage had LMC pneumonia.
CONCLUSION
Piperacillin-tazobactam, a broad-spectrum antibiotic recommended for uncertain infectious focus, was the most frequent CAP treatment and prescribed to every third patient. In addition, the current empirical antibiotic treatment accuracy was low for LMC pneumonia. Therefore, future research should focus on faster diagnostic tools for identifying the infection focus and precise microbiological testing.
Topics: Humans; Adult; Legionella pneumophila; Mycoplasma pneumoniae; Cross-Sectional Studies; Retrospective Studies; Anti-Bacterial Agents; Piperacillin, Tazobactam Drug Combination; Emergency Service, Hospital; Pneumonia; Community-Acquired Infections
PubMed: 37670282
DOI: 10.1186/s12879-023-08565-6