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Intro: Background: Obesity affects drug delivery and clearance owing to the patient's altered pharmacokinetics. In treating infection, this presents as a conundrum antibiotic dosing to achieve optimal antibiotic concentration at the same time avoiding drug toxicity. Particularly in the case of antimicrobial agents, underdosing may lead to antibiotic resistance. Method(s): Case description: We report a case of a morbidly obese (BMI=58) COVID-19 patient infected with carbapenem-sensitive multi-drug resistant (MDR) Enterobacter cloacae bacteremia, treated with ertapenem 1g twice daily and intravenous polymyxin E 9MU stat and 4.5MU twice daily for MDR Acinetobacter baumanii co-infection. He had infected huge grade IV sacral sore one month later in which intraoperative tissue culture grew phenotypically heterogeneous colonies of MDR Enterobacter cloacae with carbapenem-sensitive and carbapenem-intermediate-resistant non-carbapenemase producing colonies. He responded well clinically and biochemically with an increased dose of intravenous ciprofloxacin 800mg BD based on his actual body weight. He was discharged with oral ciprofloxacin 750mg BD for a total of six weeks. Finding(s): Discussion: Obesity is a public health crisis that has reached epidemic proportions. Obesity affects the volume distribution and renal clearance of many drugs including antibiotics. Obese patients are shown to have higher drug clearance than normal-weighted patients resulting in inadequate systemic exposure. This puts patients at risk of developing antibiotic resistant organisms. Our patient, weighing 162kg was given three different beta-lactam antibiotics to treat his infection including ertapenem in which a standard adult dose was given without body weight consideration. Possible underdosing contributed to the conversion of carbapenem susceptibility from sensitive to resistant strain. Conclusion(s): Obese individuals may need a larger ertapenem dose than their non-obese counterparts. Clinical and laboratory assessment may help in monitoring treatment response in this group of patients.Copyright © 2023
ABSTRACT
Background: The diagnosis of drug allergy requires a previous medical history suggestive of a Drug Hypersensitivity Reaction (DHR). DHRs caused by vaccines are rare (< 1/100.000 doses) and are mainly due to excipients. At the beginning of the COVID-19 vaccination, occasional cases of severe reactions were reported in patients with allergy history. This warning led to an increased demand for allergy testing to evaluate pre-vaccination risk assessment, especially due to the refusal of allergic patients to receive the vaccine. Method(s): Twenty patients were evaluated between May to July 2021, referred for allergology study prior to receiving the vaccine against COVID-19. All patients tested had allergy history. Skin tests were performed with the available excipients of the COVID-19 vaccine: polyethylene glycol (PEG-1500, 10% prick ROXALL), polysorbate 80 (tween 80 prick 0.04 -ID 0.004 mg/ml), and trometamol (prick 1 -ID 0.1 mg/ml). A telephone follow-up was subsequently performed to assess tolerance to the vaccine. Result(s): The median age of the patients was 54.5 years and ninety percent were female. (Table 1) The most frequent allergy history was adverse drug reactions (ADRs) in 18 patients (90%), followed by bronchial asthma (35%), rhinitis (25%), food allergy (25%), and dermatitis (15%). 12 patients (60%) had multiple allergic diseases. The drugs implicated in these ADRs were beta-lactam antibiotics (40%), NSAIDs (20%), radiographic contrast media (15%), and vaccines (15%). Skin tests with the excipients studied were negative in all cases. Subsequently, the COVID-19 vaccine was administered in 16 patients (80%). Six patients (30%) reported side effects expected from the vaccine and no DHRs were described. Although vaccination was recommended to all patients after the study, 4 patients (20%) refused the administration. Conclusion(s): Patients with atopic history do not require an allergology study prior to the administration of the COVID-19 vaccine. Exceptionally, it may be necessary if the patient has a history of suspected DHRs to the excipients involved. The previous allergology assessment did not prevent refusal of vaccination in 20% of the patients. (Table Presented).
ABSTRACT
Background: Only between 1% and 10% of patients labelled of penicillin allergy are allergic. The negative events associated with this condition include risk of antimicrobial treatment failure, antimicrobial resistance, side-effects from use of a broader spectrum antibiotic, and increased healthcare costs. Our objective was to know the clinical profile of hospitalized allergic patients to estimate the future need for an allergy study. Method(s): We collected data from 15 Spanish hospitals about hospitalized patients labelled as allergic to antibiotics in February 2020 and October 2020 (one-month sample) outside the peak of the Covid-19 pandemic. Result(s): 620 patients were collected, 59% women. Mean age 70.6 years (3-103). 416 patients were labelled as allergic to beta-lactams (105 aminopenicillins, 18 cephalosporins, 4 carbapenems). 41 to aminoglycosides, 26 to macrolides, 55 to quinolones and 4 to glycopeptides. The causes of hospitalization were: Respiratory infection 221 (35.6%), abdominal infection 95 (15.3%), orthopaedic surgery 58 (9.4%), urine infections 57 (9.2%), skin infections 51 (8.2%), gynaecological/ obstetric pathology 21 (3.4%) Only 163 patients (26%) had previously received a clinical allergy work-up. 70 confirmed allergy to antibiotics, however the rest 93 (74%) were not delabelled. Patients received alone or combined alternative antibiotics: 79 glycopeptides, 49 aminoglycosides, 28 macrolides, 254 quinolones, 205 beta-lactams (102 cephalosporins, 41 carbapenems and 57 aminopenicillins). 74 patients (12%) would need an immediate allergic study in order to receive first-line antibiotic, but it was only really done in 38 (6.1%). The studied antibiotics were: 15 carbapenems, 10 ceftriaxone, and others not specified. Of the 416 patients labeled as allergic to beta-lactams, 150 (36%) received beta-lactam antibiotics despite the warning in their clinical reports. Conclusion(s): Allergy to beta-lactams remains the most frequent diagnosis of allergy to antibiotics and implies treatment with second-line antibiotics. Respiratory, trauma, digestive and urinary infections are the main causes of the use of antibiotics in hospitalized patients. The underlying diseases could be a risk factor for antibiotic requirements. Some patients received beta-Lactams despite the alert with a potential risk of an allergic reaction and legal implications. The promptly allergological study would imply an improvement in the use of more specific antibiotics with a good level of security.
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Aim: To elucidate the factors that influence beta-lactam pharmacokinetic (PK) and pharmacodynamic (PD) variability in infective endocarditis (IE) and to examine optimal PK/PD target parameters for therapy. Background(s): Beta-lactam antibiotics are the mainstay of therapy for most bacterial causes of IE. Traditionally considered as agents with a broad therapeutic index there has been increasing recognition that standard doses may be subtherapeutic or toxic in critically ill patients. Optimising therapy for efficacy requires an established PK/PD target associated with clinical and microbiological cure. Method(s): Clinical and laboratory in vivo animal or human studies examining PK and/or PD of beta-lactam antibiotics in IE were eligible. Ovid MEDLINE, Embase and Cochrane Central Registry were searched using defined terms. Two authors reviewed s and full texts using Covidence software. Result(s): 62 articles were selected for review and synthesis. We identified 45 animal studies investigating the broad categories of beta-lactam diffusion into vegetations, PK/PD determinants of outcome, mode of antibiotic delivery and synergistic impact of agents. 17 human case studies/series totalling 347 participants reported antibiotic serum concentrations and clinical outcomes. Findings generally supported the importance of time-dependent killing for beta-lactams but heterogeneous data limited the determination of an optimal PK/PD target for IE treatment. Conclusion(s): Beta-lactam PK and PD in endocarditis is variable and specific to the particular antibiotic-organism combination. Timedependent killing is important, consistent with non-endocarditis studies, but there is little agreement on optimal drug exposure. Clinical studies examining various PK/PD targets in endocarditis patients are required to further inform drug selection and dosing.Copyright © 2023 Southern Society for Clinical Investigation.
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Background: Drug hypersensitivity reactions (DHRs) of the immediate type are diagnosed in approximately 1-2% per 100 thousand people. During the COVID-19 pandemic, the use of antibiotics increased, and cases of immediate reactions to these drugs became more frequent. However, due to the lack of medical centers which have the necessary conditions for carrying out provocation tests, the use of in vitro diagnostic methods for hypersensitivity reactions to antibiotics is becoming even more relevant during the pandemic. Flow CAST Basophil Activation Test (BAT) Flow Cytometry can be used for the in vitro detection of immediate type allergic reactions and hypersensitivities to suspected allergens in patients at risk for DHRs. The purpose is to study the possibility of diagnosing hypersensitivity reactions to antibiotics using BAT to antibiotics. Method(s): The Patient Questionnaire Card and the Patient Review Card were used to survey 32 (8.7%) individuals (f -56.3%, m -43.7%) who met the inclusion criteria (the presence of hypersensitivity reactions to beta-lactam antibiotics during the last 3 years). We used Flow CAST to identify the DHRs to beta-lactam antibiotics (Ceftriaxone (conc. 4 mg/ml);Cefuroxime (conc. 2.5 mg/ml);Amoxicillinum (conc. 2.5 mg/ml) from CAST Allergens for CASTFlow CAST) BUHLMANN LABORATORIES AG, Switzerland) in whole blood. Flow cytometric acquisition was performed on a flow cytometer BD FacsCalibur (USA), and 300 basophilic cells were analyzed. Result(s): The most common clinical manifestations included acute urticaria + angioedema (40.6%), generalized urticaria (28.1%), anaphylactic shock (21.9%), bronchospasm (9.4%). The percentage of patients diagnosed with an immediate reaction based on the time of its occurrence was 62.5%, whereas the percentage of patients diagnosed with an immediate reaction based on the clinical manifestations was 81.25%, which was confirmed by positive BAT results (p > 0.05). 68.75% of people with clinical manifestations of reactions to one antibiotic (ceftriaxone or amoxicillin) showed increased values on the BAT test to other beta antibiotics, which may indicate the presence of cross-reactivity between these groups of drugs. Conclusion(s): Diagnostics of immediate hypersensitivity reactions to antibiotics based on in vitro BAT is a highly accurate method. However, in cases of possible cross-reactivity between antibiotics and in cases of delayed reactions, in-depth studies are required.
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Multidrug-resistant K. pneumoniae bacterial strains producing extended range of beta-lactamases or carbapenemases are of serious clinical concern. The aim of the study was to determine the resistance factors of K. pneumoniae strains isolated from the lower respiratory tract of patients diagnosed with community-acquired pneumonia during the COVID-19 pandemic. Materials and methods. The study of resistance to antimicrobial drugs included 138 strains of K. pneumoniae isolated from the sputum of patients treated in infectious diseases monohospitals in the city of Tyumen and the Tyumen region within the period from May 2020 to June 2021. Among the strains examined, 51.4% of them were isolated from SARS-CoV-2 positive patients. The presence of resistance genes was determined by PCR in 71 strains of K. pneumoniae (34 strains from COVID-19-positive and 37 strains from COVID-19-negative patients). Identification of isolated bacterial strains was carried out according to the protein spectra by using a desktop time-of-flight mass spectrometer with matrix laser desorption MALDI-TOF MS (Bruker, Germany). The belonging of the strains to the hypermucoid phenotype was determined using the string test. Sensitivity to antimicrobial drugs was assessed in the disk diffusion method on Muller-Hinton medium. The sensitivity of culture strains to bacteriophage preparations was determined by the drop method (spot-test). In the study, we used "Polyvalent Sextaphage Pyobacteriophage" and "Purified Polyvalent Klebsiella Bacteriophage", JSC NPO Microgen, Russia. Detection of resistance genes to beta-lactam antibiotics by real-time PCR was carried out using the BakRezista kit (OOO DNA-technology, Russia). The results of the study evidence that K. pneumoniae bacteria isolated from COVID-19-positive and COVID-19-negative patients diagnosed with community-acquired pneumonia displayed a high resistance to antimicrobial drugs and commercial phage-containing drugs. Resistance of K. pneumoniae strains was recorded from 50% (to aminoglycosides and carbapenems) to 90% (to inhibitor-protected penicillins). Sensitivity to bacteriophages was noted on average in no more than 20% of strains. It is important to emphasize that strains isolated from COVID-19-positive patients more often showed a hypermucoid phenotype, suggesting a high bacterial virulence, and also showed greater resistance to all groups of antibacterial drugs examined in the study, which is confirmed by the presence of resistance genes of the ESBL group and carbapenemase. The results of the study suggest that the high level of resistance of K. pneumoniae strains isolated from COVID-19-positive patients is associated with immunosuppression provoked by the SARS-CoV-2 virus, which contributes to their colonization by more virulent strains.Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.
ABSTRACT
Multidrug-resistant K. pneumoniae bacterial strains producing extended range of beta-lactamases or carbapenemases are of serious clinical concern. The aim of the study was to determine the resistance factors of K. pneumoniae strains isolated from the lower respiratory tract of patients diagnosed with community-acquired pneumonia during the COVID-19 pandemic. Materials and methods. The study of resistance to antimicrobial drugs included 138 strains of K. pneumoniae isolated from the sputum of patients treated in infectious diseases monohospitals in the city of Tyumen and the Tyumen region within the period from May 2020 to June 2021. Among the strains examined, 51.4% of them were isolated from SARS-CoV-2 positive patients. The presence of resistance genes was determined by PCR in 71 strains of K. pneumoniae (34 strains from COVID-19-positive and 37 strains from COVID-19-negative patients). Identification of isolated bacterial strains was carried out according to the protein spectra by using a desktop time-of-flight mass spectrometer with matrix laser desorption MALDI-TOF MS (Bruker, Germany). The belonging of the strains to the hypermucoid phenotype was determined using the string test. Sensitivity to antimicrobial drugs was assessed in the disk diffusion method on Muller-Hinton medium. The sensitivity of culture strains to bacteriophage preparations was determined by the drop method (spot-test). In the study, we used “Polyvalent Sextaphage Pyobacteriophage” and “Purified Polyvalent Klebsiella Bacteriophage”, JSC NPO Microgen, Russia. Detection of resistance genes to beta-lactam antibiotics by real-time PCR was carried out using the BakRezista kit (OOO DNA-technology, Russia). The results of the study evidence that K. pneumoniae bacteria isolated from COVID-19-positive and COVID-19-negative patients diagnosed with community-acquired pneumonia displayed a high resistance to antimicrobial drugs and commercial phage-containing drugs. Resistance of K. pneumoniae strains was recorded from 50% (to aminoglycosides and carbapenems) to 90% (to inhibitor-protected penicillins). Sensitivity to bacteriophages was noted on average in no more than 20% of strains. It is important to emphasize that strains isolated from COVID-19-positive patients more often showed a hypermucoid phenotype, suggesting a high bacterial virulence, and also showed greater resistance to all groups of antibacterial drugs examined in the study, which is confirmed by the presence of resistance genes of the ESBL group and carbapenemase. The results of the study suggest that the high level of resistance of K. pneumoniae strains isolated from COVID-19-positive patients is associated with immunosuppression provoked by the SARS-CoV-2 virus, which contributes to their colonization by more virulent strains.
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Case Report: A 61-year-old man, smoker and family history of cardiovascular diseases, started oral antibiotic therapy with amoxicillin / clavulanic acid following the appearance of a dental abscess. About 30 minutes after taking the antibiotic, he complained of widespread erythema in the limbs, followed by intense itching and dyspnea. Upon arrival of the medical staff, IV cortisone and antihistamine therapy was performed with gradual and progressive resolution of the symptoms. Despite the doctors' invitation, the patient refused access to the emergency room for fear of a possible hospital infection with SARS-CoV-2. Almost two months later, due to the onset of exertional dyspnea, he is persuaded to go to the hospital for further tests. The ECG showed signs of diffuse anterolateral necrosis (Figure 1). Echocardiography showed severe left ventricular dysfunction (FE 35%) with extensive akinesia of the mid-distal SIV, apex, and anterior mid-distal wall. Myocardiocytolysis indices were negative and allergy tests positive for beta-lactam antibiotics. Subsequently he underwent coronary angiography which showed proximal occlusion of an intermediate branch (Figure 2) treated with angioplasty and drug stent release. Cardiac MRI was then performed with evidence of a large area of ischemic necrosis (subendocardial / transmural) of the antero-septal, anterior and anterolateral wall with FE 35% (Figure 3). Comment: Kounis syndrome is a clinical emergency characterized by the appearance of an acute coronary syndrome during an anaphylactic-type reaction. A correct diagnosis is of fundamental importance to limit the extent of myocardial damage as much as possible. In Kounis type 2, the mediators of the allergic reaction can cause not only vasospasm but also the activation of metalloproteases that induce the degradation of collagen with consequent rupture of pre-existing atheromatous plaques, as in our patient. Failure to perform an ECG during first aid leaves doubts about the possible allergic genesis of the episode, which however cannot be excluded with certainty. We have decided to report this clinical case to emphasize the importance of always taking into consideration the possibility of being compared with a case of Kounis when assisting a patient with an anaphylactic type reaction. (Figure Presented).
ABSTRACT
The basophil activation test (BAT) is a flow cytometric assay that evaluates the percentage of activation or degranulation of peripheral blood basophils, after “in vitro” exposure to specific allergens. In sensitized patients, the stimulation of peripheral blood basophils with a specific allergen induces or up-regulates the expression of molecules, such as CD63 and CD203c, which represent, markers of degranulation and activation of basophils, respectively. The validity of the BAT requires a negative control (sterile saline) and a positive control (anti-IgE molecules). Several studies have demonstrated the role of the BAT in supporting the diagnosis of drug, food and hymenoptera venom allergy. The BAT has shown a low sensitivity but good specificity in diagnosing allergy to drugs such as NSAIDs, beta-lactam antibiotics, quinolones and muscle relaxants. In food allergy, the sensitivity and specificity of the BAT depends on the food;in the case of peanut allergy the sensitivity reaches 96% while the specificity the 100%. In addition, the BAT is an useful tool to monitor the natural resolution of allergies and the clinical effects induced by either immunotherapy or anti-IgE treatment. Finally, the BAT has been utilized to study the pathogenetic mechanisms underlying several IgE-mediated diseases. For example, in patients affected by severe bronchial asthma, the BAT has demonstrated the ability of Staphylococcus aureus enterotoxins to induce the activation of basophils supporting the role of these enterotoxins as “triggers” of the inflammatory cascade in bronchial asthma. In patients with cystic fibrosis the BAT can be used to dis-criminate allergic bronchopulmonary aspergillosis from Aspergillus colonization. More recently, the BAT has been demonstrated as a potential diagnostic tool to evaluate allergy to the polyethylene glycol (PEG) present in the anti-SARS-CoV-2 BNT162b2 mRNA vaccine.
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Description of the case: A 79-year-old smoking patient with COPD, diabetes, previous bladder cancer, and family members positive for SARS-CoV2 was admitted to the hospital for pneumonia and severe respiratory insufficiency. During hospitalization, the nasopharynx sample was persistent negative for SARS-CoV-2, but the serology positive. CT showed signs of interstitial pneumonia. Antibiotic therapy, high-dose dexamethasone, and oxygen therapy were introduced. After an initial worsening of clinical conditions, inflammation indices normalization and marked clinical improvement until the suspension of oxygen therapy were observed. In the discharge phase, fever and increase in CRP and IL6 returned without respiratory failure. Black lesions with a necrotic ulcerated base located on the palate and posterior tongue were observed. Blood cultures were positive for Actinomyces oris, and Aspergillus galactomannan- antigen was detected. CT showed consolidations, cavitations, ground-glass opacity. Fibrobronchoscopy found tracheobronchial full-layer involvement with pharyngeal/laryngeal and bronchial obstruction by necrotic pseudomembranes. BAL was positive for SARS-CoV-2 and Aspergillus niger, and Aspergillus fumigatus. Voriconazole and beta-lactam antibiotics were started. The patient improved with the need for repeated FB to eliminate the pseudomembranes, but he died in the ICU due to heart failure. Conclusions: Hematogenous spread of Actinomyces is rare as well as pseudomembranous necrotizing oral-tracheobronchial aspergillosis, but to be considered in CoViD-19 patients receiving high doses of steroids.