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1.
Cureus ; 16(5): e61376, 2024 May.
Article in English | MEDLINE | ID: mdl-38947678

ABSTRACT

A 50-year-old man presented with fever and a generalized rash, with chronic fatigue and lymphadenopathy for a year and a half. Initial tests ruled out lymphoproliferative disorders, showing reactive hyperplasia and cytomegalovirus. Symptoms worsened after ampicillin treatment, leading to suspected drug-induced hypersensitivity syndrome (DIHS). Upon admission, amoxicillin was discontinued, and prednisolone and antiviral treatment were initiated. The patient's condition improved with this therapy. A drug-induced lymphocyte stimulation test confirmed hypersensitivity to both ampicillin and allopurinol. This case illustrates the diagnostic challenge of chronic and acute DIHS because of the rare presentation. It underscores the need for high suspicion of DIHS in patients with chronic lymphadenopathy and fatigue, particularly with recent drug exposure. Effective management involves recognizing symptoms, withdrawing the offending drug, and using corticosteroids. Viral infections like cytomegalovirus can complicate DIHS diagnosis and treatment, necessitating a comprehensive approach. This case highlights the importance of considering DIHS in differential diagnoses and the complexities of managing it alongside co-infections in rural healthcare settings.

2.
Article in English | MEDLINE | ID: mdl-38970691

ABSTRACT

To evaluate the in vitro activity of ampicillin-sulbactam and cefoperazone-sulbactam against A. baumannii using the broth disk elution testing, a total of 150 A. baumannii isolates were collected from across China between January 2019 and January 2021, including 51 carbapenem-susceptible and 99 carbapenem-resistant isolates. Broth disk elution (BDE) and the broth microdilution (BMD) method were performed for all strains. The concentration range of the BDE was 10/10 µg/mL, 20/20 µg/mL, and 30/30 µg/mL for ampicillin-sulbactam, and 37.5/15 µg/mL, 75/30 µg/mL, 112.5/45 µg/mL, and 150/60 µg/mL for cefoperazone-sulbactam, respectively. Compared with BMD, the BDE results of ampicillin-sulbactam and cefoperazone-sulbactam showed a categorical agreement of 83.3% (125/150) and 95.3% (143/150), with minor errors of 16.7% (25/150) and 4.7% (7/150), respectively. No major error or very major errors were detected. The sensitivity differences by BDE of carbapenem-resistant A. baumannii (CRAb) to different concentrations of ampicillin-sulbactam showed statistically significant (p < 0.017), while those to cefoperazone-sulbactam at 37.5/15 µg/mL, 75/30 µg/mL, and 112.5/45 µg/mL were significant (p < 0.008). However, no significant difference in sensitivity was observed between 112.5/45 µg/mL and 150/60 µg/mL (p > 0.008). In conclusion, the BDE is a reliable and convenient method to detect the in vitro activity of cefoperazone-sulbactam against A. baumannii, and the results could serve as a clinical reference value when deciding whether or not to use high-dose sulbactam for the treatment of A. baumannii infections.

3.
Int J Med Microbiol ; 316: 151626, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38954914

ABSTRACT

BACKGROUND: Aminopenicillins are recommended agents for non-invasive Haemophilus influenzae infections. One of the mechanisms of resistance to ß-lactams is the alteration of the transpeptidase region of penicillin binding protein 3 (PBP3) which is caused by mutations in the ftsI gene. It was shown that exposure to beta-lactams has a stimulating effect on increase of prevalence of H. influenzae strains with the non-enzymatic mechanism of resistance. OBJECTIVES: The aim of our study was to compare the mutational potential of ampicillin and cefuroxime in H. influenzae strains, determination of minimum inhibitory concentration and the evolution of mutations over time, focusing on amino acid substitutions in PBP3. METHODS: 30 days of serial passaging of strains in liquid broth containing increasing concentrations of ampicillin or cefuroxime was followed by whole-genome sequencing. RESULTS: On average, cefuroxime increased the minimum inhibitory concentration more than ampicillin. The minimum inhibitory concentration was increased by a maximum of 32 fold. Substitutions in the PBP3 started to appear after 15 days of passaging. In PBP3, cefuroxime caused different substitutions than ampicillin. CONCLUSIONS: Our experiment observed differences in mutation selection by ampicillin and cefuroxime. Selection pressure of antibiotics in vitro generated substitutions that do not occur in clinical strains in the Czech Republic.

4.
Article in English | MEDLINE | ID: mdl-38958001

ABSTRACT

Background: The optimal ampicillin-sulbactam dosing regimen for carbapenem-susceptible Acinetobacter baumannii isolates in critically ill trauma patients has not been clearly defined. One strategy to provide the adequate sulbactam dose includes high-dose continuous infusion. Case(s) Description: We present three cases of critically ill trauma patients with augmented renal clearance treated with high-dose ampicillin-sulbactam through an intravenous continuous infusion for ventilator-associated pneumonia. All A. baumannii isolates were susceptible to sulbactam with low minimum inhibitory concentrations. All achieved clinical cure at the end of therapy and no recurrent pneumonia was noted. No clinically substantial adverse effect attributable to ampicillin-sulbactam therapy occurred. Discussion: There is limited evidence to endorse high-dose, continuous infusion ampicillin-sulbactam for treatment of infections caused by carbapenem-susceptible A. baumannii. This report presents three critically ill trauma patients with augmented renal clearance that achieved positive clinical outcomes with higher doses of ampicillin-sulbactam administered through a continuous infusion.

5.
Int J Nanomedicine ; 19: 5397-5418, 2024.
Article in English | MEDLINE | ID: mdl-38863647

ABSTRACT

Background: The healing of burn wounds is a complicated physiological process that involves several stages, including haemostasis, inflammation, proliferation, and remodelling to rebuild the skin and subcutaneous tissue integrity. Recent advancements in nanomaterials, especially nanofibers, have opened a new way for efficient healing of wounds due to burning or other injuries. Methods: This study aims to develop and characterize collagen-decorated, bilayered electrospun nanofibrous mats composed of PVP and PVA loaded with Resveratrol (RSV) and Ampicillin (AMP) to accelerate burn wound healing and tissue repair. Results: Nanofibers with smooth surfaces and web-like structures with diameters ranging from 200 to 400 nm were successfully produced by electrospinning. These fibres exhibited excellent in vitro properties, including the ability to absorb wound exudates and undergo biodegradation over a two-week period. Additionally, these nanofibers demonstrated sustained and controlled release of encapsulated Resveratrol (RSV) and Ampicillin (AMP) through in vitro release studies. The zone of inhibition (ZOI) of PVP-PVA-RSV-AMP nanofibers against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was found 31±0.09 mm and 12±0.03, respectively, which was significantly higher as compared to positive control. Similarly, the biofilm study confirmed the significant reduction in the formation of biofilms in nanofiber-treated group against both S. aureus and E. coli. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis proved the encapsulation of RSV and AMP successfully into nanofibers and their compatibility. Haemolysis assay (%) showed no significant haemolysis (less than 5%) in nanofiber-treated groups, confirmed their cytocompatibility with red blood cells (RBCs). Cell viability assay and cell adhesion on HaCaT cells showed increased cell proliferation, indicating its biocompatibility as well as non-toxic properties. Results of the in-vivo experiments on a burn wound model demonstrated potential burn wound healing in rats confirmed by H&E-stained images and also improved the collagen synthesis in nanofibers-treated groups evidenced by Masson-trichrome staining. The ELISA assay clearly indicated the efficient downregulation of TNF-alpha and IL-6 inflammatory biomarkers after treatment with nanofibers on day 10. Conclusion: The RSV and AMP-loaded nanofiber mats, developed in this study, expedite burn wound healing through their multifaceted approach.


Subject(s)
Ampicillin , Burns , Collagen , Escherichia coli , Nanofibers , Polyvinyl Alcohol , Povidone , Resveratrol , Staphylococcus aureus , Wound Healing , Resveratrol/pharmacology , Resveratrol/chemistry , Resveratrol/administration & dosage , Resveratrol/pharmacokinetics , Nanofibers/chemistry , Burns/drug therapy , Wound Healing/drug effects , Animals , Collagen/chemistry , Povidone/chemistry , Staphylococcus aureus/drug effects , Polyvinyl Alcohol/chemistry , Humans , Escherichia coli/drug effects , Ampicillin/pharmacology , Ampicillin/chemistry , Ampicillin/pharmacokinetics , Ampicillin/administration & dosage , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/administration & dosage , Rats , Biofilms/drug effects , Male
6.
Infect Drug Resist ; 17: 2329-2335, 2024.
Article in English | MEDLINE | ID: mdl-38882654

ABSTRACT

The escalating incidence of infective endocarditis (IE) caused by aminoglycoside-resistant Enterococcus is a growing concern for clinicians. This issue is particularly pronounced in elderly patients, who face an elevated risk of renal damage during antibiotic treatment, thereby limiting available pharmacological options. Furthermore, elderly patients often present with multiple comorbidities, leading to heightened mortality rates. In this article, we present a case involving an elderly male patient who sought medical attention on two separate occasions due to inflammation of the lower extremities and lumbosacral pain. Subsequent diagnosis revealed infective endocarditis (IE) caused by high-level gentamicin-resistant Enterococcus faecalis through blood culture and echocardiography. The patient also experienced peripheral and cerebral arterial embolism, secondary spine infection, and subsequent heart failure, highlighting the severity of the clinical situation. Following an initial 10-day course of vancomycin and ceftriaxone therapy, the patient developed renal impairment, necessitating a switch to bactericidal therapy with ampicillin in combination with ceftriaxone. Additionally, aortic valve replacement was performed during this period. Ultimately, the patient achieved clinical remission. This case underscores the critical importance of prompt and accurate diagnosis, appropriate antibiotic selection, and timely surgical intervention in enhancing the prognosis of elderly patients with IE.

7.
Braz J Microbiol ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38831174

ABSTRACT

Multidrug-resistant pathogenic vibrios are a crisis of concern as they cause multiple illnesses, including gastroenteritis in humans and acute hepatopancreatic necrosis in aquaculture. In the current study, we investigated the prevalence of the beta-lactamase gene CTX-M-group 1 in Vibrio spp. (Vibrio cholerae and Vibrio parahaemolyticus) from the water and sediment of urban tropical mangrove ecosystems of Kerala, southwest India. A total of 120 isolates of Vibrio spp. were tested for antibiotic susceptibility to 14 antibiotics. In water, ampicillin resistance was very high in isolates of V. cholerae (94.1%, n = 17) and V. parahaemolyticus (89.1%, n = 46). 26.9% of V. parahaemolyticus and 14.2% of V. cholerae harbored the CTX-M-group 1 gene in water samples. Compared to V. cholerae, the CTX-M-group 1 gene was exclusively hosted by V. parahaemolyticus (49%) in sediment samples. A significant difference in the prevalence of the CTX-M-group 1 gene was observed among Vibrio spp. in both water and sediment samples (p < 0.05). The results revealed the presence of multidrug-resistant and beta-lactamase harboring Vibrio spp. in mangrove ecosystems, which may have evolved as a consequence of the misuse and abuse of broad-spectrum antibiotics as prophylaxis in human health care and aquaculture.

8.
Heliyon ; 10(10): e31617, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38826735

ABSTRACT

The detection of ampicillin plays a crucial role in managing and monitoring its usage and resistance. This study introduces a simple and effective biosensor for ampicillin detection, utilizing the unique absorbance features of Mn-doped ZnS capped by chitosan micromaterials in conjunction with ß-lactamase activity. The biosensors can detect ampicillin concentrations from 13.1 to 72.2 µM, with a minimum detection limit of 2.93 µM for sensors based on 300 mg/L of the sensing material. In addition, these sensors show high specificity for ampicillin over other antibiotics such as penicillin, tetracycline, amoxicillin, cephalexin, and a non-antibiotic-glucose. This specificity is demonstrated by an enhancing effect when beta-lactamase is used, as opposed to a quenching effect observed at 340 nm in the absorbance spectrum when no beta-lactamase is present. This research highlights the potential of affordable chitosan-capped Mn-doped ZnS micromaterials for detecting ampicillin through simple absorbance measurements, which could improve the monitoring of antibiotics in both clinical and environmental settings.

9.
J Neuroimmunol ; 392: 578374, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38797060

ABSTRACT

We aimed to investigate ampicillin (AMP) mechanisms in microbiota-gut-brain axis. We evaluated its effect on two gut and brain regions and behavioral performances. We administred AMP (1 g/l) to BALB/c mice for 21 days. Then, we analyzed body weigth change, stool consistency scoring, gut length, intestinal microbiota composition, nitric oxide synthase 2 (NOS2) expression and tissue integrity. We subsequently evaluated NOS2, GFAP, CD68 and NFL cerebral expression and spatial memory.Interestingly, our data showed gut microbiota disruption, NOS2 upregulation and tissue damage, associated to cerebral NOS2, GFAP, CD68 and NFL over-expression and behavioral alteration. Antiobiotic therapy should be prescribed with great caution.


Subject(s)
Ampicillin , Brain-Gut Axis , Dysbiosis , Gastrointestinal Microbiome , Mice, Inbred BALB C , Nitric Oxide Synthase Type II , Animals , Mice , Ampicillin/pharmacology , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/physiology , Dysbiosis/chemically induced , Nitric Oxide Synthase Type II/metabolism , Male , Brain-Gut Axis/physiology , Brain-Gut Axis/drug effects , Neuroinflammatory Diseases/metabolism , Anti-Bacterial Agents/pharmacology , Spatial Memory/drug effects , Spatial Memory/physiology , Disease Models, Animal , Neurodegenerative Diseases/chemically induced
10.
IDCases ; 36: e01965, 2024.
Article in English | MEDLINE | ID: mdl-38699529

ABSTRACT

Background: Listeria monocytogenes, a Gram-positive bacillus, primarily affects immunocompromised individuals. Endocarditis is a rare but severe complication of L. monocytogenes bacteremia, irrespective of native or prosthetic valves. While there is no standardized treatment, the use of ampicillin proves effective in most cases. Surgical intervention is reserved for cases involving valve dehiscence, heart failure, or myocardial abscess. Case presentation: A 54-year-old female, with mitral valve replacement, presented with fever, chest pain and dyspnea at rest. Patient was initially diagnosed with bacterial pneumonia; however, subsequent evaluation revealed L. monocytogenes bacteremia, resulting in endocarditis. Surgical management was contraindicated due to multiple prior valve replacement surgeries. Symptoms resolution, along with improvements in echocardiographic and clinical parameters, was achieved through extended antibiotic treatment only with no surgical intervention. Conclusion - key takeaways: This case underscores the critical importance of individualized treatment approaches in endocarditis, particularly in patients with surgery approach contraindication, and emphasized the success achieved through ampicillin-based management.

11.
Molecules ; 29(10)2024 May 09.
Article in English | MEDLINE | ID: mdl-38792087

ABSTRACT

In this work, we present the modification of a medical-grade silicone catheter with the N-vinylimidazole monomer using the grafting-from method at room temperature and induced by gamma rays. The catheters were modified by varying the monomer concentration (20-100 vol%) and the irradiation dose (20-100 kGy). Unlike the pristine material, the grafted poly(N-vinylimidazole) chains provided the catheter with hydrophilicity and pH response. This change allowed for the functionalization of the catheters to endow it with antimicrobial features. Thus, the quaternization of amines with iodomethane and bromoethane was performed, as well as the immobilization of silver and ampicillin. The inhibitory capacity of these materials, functionalized with antimicrobial agents, was challenged against Escherichia coli and Staphylococcus aureus strains, showing variable results, where loaded ampicillin was amply better at eliminating bacteria.


Subject(s)
Escherichia coli , Imidazoles , Silicones , Staphylococcus aureus , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Silicones/chemistry , Imidazoles/chemistry , Imidazoles/pharmacology , Catheters/microbiology , Microbial Sensitivity Tests , Polyvinyls/chemistry , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Ampicillin/chemistry , Ampicillin/pharmacology , Gamma Rays
13.
Mikrochim Acta ; 191(5): 294, 2024 05 02.
Article in English | MEDLINE | ID: mdl-38698253

ABSTRACT

Early transition metal carbides (MXene) hybridized by precious metals open a door for innovative electrochemical biosensing device design. Herein, we present a facile one-pot synthesis of gold nanoparticles (AuNPs)-doped two-dimensional (2D) titanium carbide MXene nanoflakes (Ti3C2Tx/Au). Ti3C2Tx MXene exhibits high electrical conductivity and yields synergistic signal amplification in conjunction with AuNPs leading to excellent electrochemical performance. Thus Ti3C2Tx/Au hybrid nanostructure can be used as an electrode platform for the electrochemical analysis of various targets. We used screen-printed electrodes modified with the Ti3C2Tx/Au electrode and functionalized with different biorecognition elements to detect and quantify an antibiotic, ampicillin (AMP), and a mycotoxin, fumonisin B1 (FB1). The ultralow limits of detection of 2.284 pM and 1.617 pg.mL-1, which we achieved respectively for AMP and FB1 are far lower than their corresponding maximum residue limits of 2.8 nM in milk and 2 to 4 mg kg-1 in corn products for human consumption set by the United States Food and Drug Administration. Additionally, the linear range of detection and quantification of AMP and FB1 were, respectively, 10 pM to 500 nM and 10 pg mL-1 to 1 µg mL-1. The unique structure and excellent electrochemical performance of Ti3C2Tx/Au nanocomposite suggest that it is highly suitable for anchoring biorecognition entities such as antibodies and oligonucleotides for monitoring various deleterious contaminants in agri-food products.


Subject(s)
Ampicillin , Electrochemical Techniques , Fumonisins , Gold , Limit of Detection , Metal Nanoparticles , Titanium , Fumonisins/analysis , Gold/chemistry , Ampicillin/analysis , Ampicillin/chemistry , Metal Nanoparticles/chemistry , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Titanium/chemistry , Biosensing Techniques/methods , Milk/chemistry , Anti-Bacterial Agents/analysis , Electrodes , Food Contamination/analysis , Animals
14.
J Pharm Pract ; : 8971900241256726, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780407

ABSTRACT

INTRODUCTION: Peritoneal dialysis (PD) - associated peritonitis is a serious complication of peritoneal dialysis (PD). The 2022 International Society of Peritoneal Dialysis (ISPD) guidelines do not recommend intraperitoneal (IP) ampicillin for treatment of Enterococcal PD - associated peritonitis. To date, there is no in vivo data to support use of IP ampicillin for the treatment of Enterococcus faecalis. CASE DESCRIPTION: A 69-year-old man with a past medical history of end stage kidney disease (ESKD) requiring continuous cycling peritoneal dialysis (CCPD) was admitted to the hospital and treated for peritonitis with E. faecalis. The patient's CCPD prescription was 2.5% Dianeal with 5 total exchanges. IP ampicillin was added to the first 4 exchanges and additional ampicillin was added to the last fill. The patient successfully completed the treatment course with clinical cure. DISCUSSION: The use of IP ampicillin for E. faecalis peritonitis is controversial and previously lacked compelling clinical evidence for or against its use. This case demonstrates treatment of peritonitis using a modified dosing strategy with ampicillin added to each CCPD exchange and last fill. The loss of ampicillin antimicrobial activity reported in vitro with E. faecalis was not supported by this case.

15.
Acta Paediatr ; 113(7): 1694-1700, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38578153

ABSTRACT

AIM: To compare the prophylactic efficacy of ampicillin and clindamycin against vertical transmission of group B Streptococcus from mothers to their infants by evaluating the rates of group B Streptococcus colonisation. METHODS: We retrospectively extracted data for mothers who delivered at Showa University Northern Yokohama Hospital between 1 October 2017 and 31 March 2021 and tested positive for antepartum group B Streptococcus, and their infants. The chi-square test was used to compare the rates of group B Streptococcus colonisation, sepsis, and meningitis. We conducted a multivariate logistic regression analysis, including the time interval between membrane rupture and delivery, chorioamnionitis, and maternal intrapartum fever (≥38.0°C). RESULTS: Two hundred fifty-nine mothers and their infants were eligible. Ampicillin and clindamycin were administered to 150 and 109 mothers, respectively. In the ampicillin and clindamycin groups, 12.0% (18/150) and 37.6% (41/109) infants were group B Streptococcus positive, respectively. The rate of group B Streptococcus colonisation among infants was significantly lower in the ampicillin group (p < 0.001). Multivariate regression analysis showed similar results (p < 0.001). No sepsis or meningitis cases were observed in either group. CONCLUSION: Prophylactic efficacy of clindamycin against the vertical transmission of group B Streptococcus is lower than that of ampicillin.


Subject(s)
Ampicillin , Anti-Bacterial Agents , Clindamycin , Infectious Disease Transmission, Vertical , Streptococcal Infections , Streptococcus agalactiae , Humans , Ampicillin/therapeutic use , Clindamycin/therapeutic use , Female , Infectious Disease Transmission, Vertical/prevention & control , Retrospective Studies , Streptococcal Infections/prevention & control , Streptococcal Infections/transmission , Pregnancy , Anti-Bacterial Agents/therapeutic use , Infant, Newborn , Adult , Antibiotic Prophylaxis/methods , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/drug therapy
16.
mBio ; 15(5): e0017024, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38564699

ABSTRACT

Penicillin-binding protein 5 (PBP5) of Enterococcus faecium (Efm) is vital for ampicillin resistance (AMP-R). We previously designated three forms of PBP5, namely, PBP5-S in Efm clade B strains [ampicillin susceptible (AMP-S)], PBP5-S/R (AMP-S or R), and PBP5-R (AMP-R) in clade A strains. Here, pbp5 deletion resulted in a marked reduction in AMP minimum inhibitory concentrations (MICs) to 0.01-0.09 µg/mL for clade B and 0.12-0.19 µg/mL for clade A strains; in situ complementation restored parental AMP MICs. Using D344SRF (lacking ftsW/psr/pbp5), constructs with ftsWA/psrA (from a clade A1 strain) cloned upstream of pbp5-S and pbp5-S/R alleles resulted in modest increases in MICs to 3-8 µg/mL, while high MICs (>64 µg/mL) were seen using pbp5 from A1 strains. Next, using ftsW ± psr from clade B and clade A/B and B/A hybrid constructs, the presence of psrB, even alone or in trans, resulted in much lower AMP MICs (3-8 µg/mL) than when psrA was present (MICs >64 µg/mL). qRT PCR showed relatively greater pbp5 expression (P = 0.007) with pbp5 cloned downstream of clade A1 ftsW/psr (MIC >128 µg/mL) vs when cloned downstream of clade B ftsW/psr (MIC 4-16 µg/mL), consistent with results in western blots. In conclusion, we report the effect of clade A vs B psr on AMP MICs as well as the impact of pbp5 alleles from different clades. While previously, Psr was not thought to contribute to AMP MICs in Efm, our results showed that the presence of psrB resulted in a major decrease in Efm AMP MICs. IMPORTANCE: The findings of this study shed light on ampicillin resistance in Enterococcus faecium clade A strains. They underscore the significance of alterations in the amino acid sequence of penicillin-binding protein 5 (PBP5) and the pivotal role of the psr region in PBP5 expression and ampicillin resistance. Notably, the presence of a full-length psrB leads to reduced PBP5 expression and lower minimum inhibitory concentrations (MICs) of ampicillin compared to the presence of a shorter psrA, regardless of the pbp5 allele involved. Additionally, clade B E. faecium strains exhibit lower AMP MICs when both psr alleles from clades A and B are present, although it is important to consider other distinctions between clade A and B strains that may contribute to this effect. It is intriguing to note that the divergence between clade A and clade B E. faecium and the subsequent evolution of heightened AMP MICs in hospital-associated strains appear to coincide with changes in Pbp5 and psr. These changes in psr may have resulted in an inactive Psr, facilitating increased PBP5 expression and greater ampicillin resistance. These results raise the possibility that a mimicker of PsrB, if one could be designed, might be able to lower MICs of ampicillin-resistant E. faecium, thus potentially resorting ampicillin to our therapeutic armamentarium for this species.


Subject(s)
Anti-Bacterial Agents , Enterococcus faecium , Penicillin-Binding Proteins , beta-Lactam Resistance , Ampicillin/pharmacology , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , beta-Lactam Resistance/genetics , Enterococcus faecium/genetics , Enterococcus faecium/drug effects , Enterococcus faecium/metabolism , Genome, Bacterial , Microbial Sensitivity Tests , Penicillin-Binding Proteins/genetics , Penicillin-Binding Proteins/metabolism
17.
World J Clin Cases ; 12(8): 1530-1535, 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38576803

ABSTRACT

BACKGROUND: The role of primary-level medical pharmacists in medical institutions in China is limited; therefore, it is necessary to explore the role of pharmacists in the process of drug treatment. CASE SUMMARY: A Chinese pharmacist participated in the complete treatment of a patient with a duodenal ulcer. The rationale for drug treatment was evaluated, and adjustments were made to the antacid and anti-infective regimen, as well as the dose and frequency of administration. Body temperature, routine blood examination, and adverse drug reactions were strictly monitored. During treatment, the pharmacist recommended anti-infective therapy with ampicillin-sulbactam, which effectively controlled the infection. Additionally, the pharmacist suggested changing famotidine to lansoprazole for acid suppression and gastroprotective treatment, combined with Chinese patent medicine such as Kangfuxin Liquid. This is the first case report of a pharmacist in primary-level medical institutions adjusting drug use for patients with duodenal ulcer and pulmonary infection. CONCLUSION: A pharmacist participated in the treatment process, provided individualized medication adjustment, and achieved good clinical results.

18.
Cureus ; 16(3): e55800, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38586725

ABSTRACT

Listeria monocytogenes, a gram-positive bacillus and an intracellular pathogen, is an uncommon cause of illness in the general population. During pregnancy, a perinatal infection can lead to serious complications such as abortion, stillbirth, neonatal sepsis, and meningitis. We present two cases of neonatal meningitis caused by Christie, Atkins, Munch-Peterson (CAMP)-negative Listeria monocytogenes. In the first case, a seven-day-old female term neonate delivered vaginally, presented with high-grade fever and refusal to feed. In view of the suspected late-onset sepsis, a septic workup, including cerebrospinal fluid analysis, was conducted. CSF culture reports obtained showed a growth consistent with Listeria monocytogenes, which was CAMP test negative and susceptible to the penicillin group of drugs, cotrimoxazole, erythromycin, and meropenem. The isolate was identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and confirmed by 16S rRNA sequencing. The blood culture was sterile. At 48 hours of admission, the neonate clinically deteriorated with fluctuation in oxygen saturation below 95% at room air. Thus, she was electively intubated and connected to the mechanical ventilator with appropriate settings. The antibiotics were upgraded to meropenem from the empirical antibiotic therapy. The neonate showed clinical improvement within the next 24 hours of initiating antibiotics according to culture susceptibility and was gradually weaned from the mechanical ventilator to continuous positive airway pressure (CPAP). After 24 hours, she was able to maintain normal saturation at room air. In the second case, an 11-day-old low birth weight neonate, small for gestational age, was presented to the NICU with complaints of loose stools, fever, and refusal to feed for the past two days. In view of the suspected sepsis, relevant investigations were carried out while initiating empirical antibiotics IV piperacillin-tazobactam and IV amikacin for the neonate. Meanwhile, there was a dip in oxygen saturation noted on room air for the neonate and he/she was mechanically ventilated. The CSF culture grew Listeria monocytogenes,which was identified using MALDI-TOF MS and confirmed by 16S rRNA sequencing. The isolate tested negative for the CAMP test and was susceptible to ampicillin, penicillin, cotrimoxazole, erythromycin, and meropenem. The blood culture was sterile. The antibiotics were upgraded to meropenem from the empirical antibiotic therapy, the patient's condition improved, and the baby was eventually discharged.

19.
Eur J Pharmacol ; 974: 176611, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38663540

ABSTRACT

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract for which treatment options remain limited. In this study, we used a dual-luciferase-based screening of an FDA-approved drug library, identifying Bazedoxifene (BZA) as an inhibitor of the NF-κB pathway. We further investigated its therapeutic effects in a dextran sodium sulfate (DSS)-induced colitis model and explored its impact on gut microbiota regulation and the underlying molecular mechanisms. Our results showed that BZA significantly reduced DSS-induced colitis symptoms in mice, evidenced by decreased colon length shortening, lower histological scores, and increased expression of intestinal mucosal barrier-associated proteins, such as Claudin 1, Occludin, Zo-1, Mucin 2 (Muc2), and E-cadherin. Used independently, BZA showed therapeutic effects comparable to those of infliximab (IFX). In addition, BZA modulated the abundance of gut microbiota especially Bifidobacterium pseudolongum, and influenced microbial metabolite production. Crucially, BZA's alleviation of DSS-induced colitis in mice was linked to change in gut microbiota composition, as evidenced by in vivo gut microbiota depletion and fecal microbiota transplantation (FMT) mice model. Molecularly, BZA inhibited STAT3 and NF-κB activation in DSS-induced colitis in mice. In general, BZA significantly reduced DSS-induced colitis in mice through modulating the gut microbiota and inhibiting STAT3 and NF-κB activation, and its independent use demonstrated a therapeutic potential comparable to IFX. This study highlights gut microbiota's role in IBD drug development, offering insights for BZA's future development and its clinical applications.


Subject(s)
Colitis , Dextran Sulfate , Gastrointestinal Microbiome , NF-kappa B , STAT3 Transcription Factor , Signal Transduction , Animals , NF-kappa B/metabolism , STAT3 Transcription Factor/metabolism , Colitis/chemically induced , Colitis/drug therapy , Colitis/metabolism , Colitis/microbiology , Colitis/pathology , Gastrointestinal Microbiome/drug effects , Mice , Signal Transduction/drug effects , Indoles/pharmacology , Indoles/therapeutic use , Mice, Inbred C57BL , Disease Models, Animal , Colon/drug effects , Colon/pathology , Colon/metabolism , Colon/microbiology , Male , Humans
20.
Biochem Biophys Res Commun ; 714: 149974, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38663094

ABSTRACT

Due to the rapid emergence of antibiotic resistant new bacterial strains and new infections, there is an urgent need for novel or newly modified and efficient alternatives of treatment. However, conventional antibiotics are still used in therapeutic settings but their efficacy is uncertain due to the rapid evolution of drug resistance. In the present study, we have synthesized a new derivative of conventional antibiotic ampicillin using SN2-type substitution reaction. NMR and mass analysis of the newly synthesized derivative of ampicillin confirmed it as ampicillin-bromo-methoxy-tetralone (ABMT). Importantly, ABMT is revealed to have efficient activity against Staphylococcus aureus (S. aureus) with a MIC value of 32 µg ml-1 while ampicillin was not effective, even at 64 µg ml-1 of concentration. Electron microscopy results confirmed the membrane-specific killing of S. aureus at 1 h of treatment. Additionally, molecular docking analysis revealed a strong binding affinity of ABMT with ß-lactamase via the formation of a closed compact bridge. Our findings, avail a new derivative of ampicillin that could be a potential alternative to fight ampicillin-resistant bacteria possibly by neutralizing the ß-lactamase action.


Subject(s)
Ampicillin , Anti-Bacterial Agents , Microbial Sensitivity Tests , Molecular Docking Simulation , Staphylococcus aureus , Ampicillin/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Staphylococcus aureus/drug effects , Tetralones/pharmacology , Tetralones/chemistry , Tetralones/chemical synthesis , Ampicillin Resistance , beta-Lactamases/metabolism
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