Alergie na antibiotika představují narůstající problém současné medicíny. Omezují léčebné možnosti, a ne vždy opodstatněně. Nejčastěji je udávána alergie na antibiotika penicilinové řady. Je však až desetinásobně nadhodnocená. Konfirmace skutečné alergie se opírá o detailní rozbor průběhu nežádoucí reakce, kožní testy a výběrově laboratorní a provokační testy. Článek nabízí přehled klinických forem a základní orientaci v diagnostice a managementu alergií na antibiotika.
Antibiotic allergies represent a growing issue in the current medicine. They limit treatment options, and not always justifiably. The majority of cases is labelled as having penicillin allergy. However, penicillin allergy is up to ten times overdiagnosed. The true allergy confirmation is based on detailed analysis of the course of the adverse event, skin tests, and, selectively, laboratory and provocation tests. This paper offers a review of clinical manifestations and a basic orientation in diagnosis and management of antibiotic allergies.
There have been studies on antibiotic use concerning lung cancer and its potential impact on carcinogenesis and microbiome. However, subsequent research has failed to support these associations consistently. In terms of the potential carcinogenic of antibiotics on lung cancer, the available evidence has not been sufficient to draw any definitive conclusions. Maintaining immune homeostasis and preventing pathogen invasion is critically dependent on the microbiome. The subtle balance of the body microbiota, including the lungs, is susceptible to disruption by antibiotic use. There is an association between disruptions of the lung microbiome and respiratory diseases, including lung cancer, and decreased efficacy of treatments. Patients with lung cancer are often indicated for antibiotic treatment due to respiratory infections or other comorbidities. Pulmonary infections in the area of undetected lung tumors are not uncommon. They can be an early sign of malignancy, which may explain the association between antibiotic use and lung cancer diagnosis. Antibiotic use can also affect the effectiveness of immune checkpoint inhibitor therapy. Studies suggest that antibiotic use can impair the efficacy of immune checkpoint inhibitor therapy in lung cancer patients, particularly around the time when treatment is initiated. These findings require further study, understanding underlying mechanisms, and identifying microbiota signatures associated with treatment response.
AIM: The objective of this study was to evaluate off-label high-dose ceftazidime population pharmacokinetics in cancer patients with suspected or proven extensively drug-resistant (XDR) Pseudomonas aeruginosa infections and then to compare the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target after standard and off-label high-dose regimens using population model-based simulations. A further aim was to clinically observe the occurrence of adverse effects during the off-label high-dose ceftazidime treatment. METHODS: In patients treated with off-label high-dose ceftazidime (3 g every 6 h), blood samples were collected and ceftazidime serum levels measured using LC-MS/MS. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were then used to compare standard and high-dose regimens for PK/PD target attainment. RESULTS: A total of 14 cancer patients with serious infection suspected of XDR P. aeruginosa aetiology were eligible for PK analysis. XDR P. aeruginosa was confirmed in 10 patients as the causative pathogen. Population ceftazidime volume of distribution was 13.23 L, while clearance started at the baseline of 1.48 L/h and increased by 0.0076 L/h with each 1 mL/min/1.73 m2 of eGFR. High-dose regimen showed significantly higher probability of target attainment (i.e., 86% vs. 56% at MIC of 32 mg/L). This was translated into a very low mortality rate of 20%. Only one case of reversible neurological impairment was observed. CONCLUSION: We proved the superiority of the ceftazidime off-label high-dose regimen in PK/PD target attainment with very low occurrence of adverse effects. The off-label high-dose regimen should be used to optimize treatment of XDR P. aeruginosa infections.
- MeSH
- antibakteriální látky škodlivé účinky farmakokinetika MeSH
- ceftazidim škodlivé účinky farmakokinetika MeSH
- chromatografie kapalinová MeSH
- lidé MeSH
- metoda Monte Carlo MeSH
- mikrobiální testy citlivosti MeSH
- nádory * komplikace farmakoterapie MeSH
- off-label použití léčivého přípravku MeSH
- pseudomonádové infekce * farmakoterapie MeSH
- Pseudomonas aeruginosa MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. "European Registry on H. pylori Management (Hp-EuReg)" data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18-59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p < 0.05). The overall second-line mITT treatment effectiveness was 84% in both groups. The effectiveness of the most frequent first- and second-line triple therapies was suboptimal (< 90%) in both groups. Optimal efficacy (≥ 90%) was achieved by using bismuth and non-bismuth-based quadruple therapies. In conclusion, the approach to the diagnostics and treatment of H. pylori infection did not generally differ between younger and older patients. Main differences were reported in the concurrent medications, allergy to penicillin and adverse events both in first- and second-line treatment. Optimal effectiveness rates were mostly achieved by using bismuth and non-bismuth-based quadruple therapies. No clinically relevant differences in the effectiveness between the age groups were observed.
- MeSH
- alergie * farmakoterapie MeSH
- antibakteriální látky škodlivé účinky MeSH
- bismut terapeutické užití MeSH
- Helicobacter pylori * MeSH
- infekce vyvolané Helicobacter pylori * farmakoterapie epidemiologie MeSH
- inhibitory protonové pumpy škodlivé účinky MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- peniciliny terapeutické užití MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Alergie na antibiotika představují narůstající problém současné medicíny. Omezují léčebné možnosti, a ne vždy opodstatněně. Nejčastěji je udávána alergie na antibiotika penicilinové řady. Je však až desetinásobně nadhodnocená. Konfirmace skutečné alergie se opírá o detailní rozbor průběhu nežádoucí reakce, kožní testy a výběrově laboratorní a provokační testy. Článek nabízí přehled klinických forem a základní orientaci v diagnostice a managementu alergií na antibiotika.
Antibiotic allergies represent a growing issue in the current medicine. They limit treatment options, and not always justifiably. The majority of cases is labelled as having penicillin allergy. However, penicillin allergy is up to ten times overdiagnosed. The true allergy confirmation is based on detailed analysis of the course of the adverse event, skin tests, and, selectively, laboratory and provocation tests. This paper offers a review of clinical manifestations and a basic orientation in diagnosis and management of antibiotic allergies.
- MeSH
- anafylaxe * chemicky indukované diagnóza terapie MeSH
- antibakteriální látky škodlivé účinky MeSH
- antiflogistika nesteroidní škodlivé účinky MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- kožní testy MeSH
- léková alergie diagnóza patologie terapie MeSH
- lidé MeSH
- nežádoucí účinky léčiv epidemiologie MeSH
- rizikové faktory MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
Klostrídiová kolitída bola dlhodobo považovaná za infekciu asociovanú s hospitalizáciou a súčasnou antibiotickou liečbou. Narastajúci počet prípadov v komunite však v posledných rokoch viedol k prehodnoteniu tradičného chápania jej epidemiologických charakteristík. Komunitné formy boli navyše mnohokrát zaznamenané u detí, mladých dospelých či ľudí bez komorbidít a s negatívnou anamnézou užívania antibiotík v predchorobí. Uvedené skupiny boli tradične považované za nízkorizikové pre vznik ochorenia. Mnohé štúdie tak prirodzene skúmali vplyv asymptomatických prenášačov Clostridioides difficile, vrátane novorodencov a dojčiat, na prenos pôvodcu ochorenia v komunite. Predmetom výskumu sa stal aj výskyt tejto baktérie u zvierat, v potrave a environmentálnom prostredí. Snahou bolo ozrejmiť úlohu uvedených faktorov v šírení pôvodcu v komunitných podmienkach. V článku sumarizujeme aktuálne poznatky o potvrdených a potencionálnych rizikových faktoroch komunitnej formy klostrídiovej kolitídy, spoločne s výsledkami štúdií skúmajúcich charakteristiky týchto pacientov. Zároveň prinášame informácie o problematike výskytu klostrídiovej kolitídy v detskej populácii, ktorá je s komunitnou formou infekcie úzko previazaná.
Clostridioides difficile colitis has long been considered an infection associated with hospitalization and concomitant antibiotic treatment. However, the increasing number of community cases in recent years has led to a reassessment of the traditional understanding of its epidemiological characteristics. In addition, community-associated forms have been reported many times in children, young adults, or people without comorbidities and with a negative history of antibiotic use in the pre-disease period. These groups have traditionally been considered low risk for the development of the infection. Thus, many studies have naturally investigated the impact of asymptomatic Clostridioides difficile carriers, including neonates and infants, on the transmission of the causative agent in the community. The prevalence of this bacterium in animals, in food and in the environmental setting has also been the subject of research. The goal was to elucidate the role of these factors in the spread of the agent in community settings. In this article, we summarize the current knowledge on confirmed and potential risk factors for community-acquired Clostridioides difficile infection, together with the results of studies examining patient characteristics. We also provide information on the issue of Clostridioides difficile infection in the paediatric population, which is closely intertwined with the community-acquired form of the infection.
Autori popisujú prípad 90-ročného pacienta s výsevom vzniknutým niekoľko hodín po podaní amoxicilín klavulanátu. Na základe prítomnosti charakteristických klinických prejavov bola stanovená diagnóza symetrický liekmi navodený intertriginózny a flexurálny exantém. Prípad bol z diferenciálne-diagnostického hľadiska komplikovaný aj koexistenciou arteficiálne vzniknutého edému dolnej končatiny. Autori uvádzajú prehľad súčasných poznatkov o diagnostických a terapeutických možnostiach v manažmente tejto zriedkavej klinickej entity.Autori popisujú prípad 90-ročného pacienta s výsevom vzniknutým niekoľko hodín po podaní amoxicilín klavulanátu. Na základe prítomnosti charakteristických klinických prejavov bola stanovená diagnóza symetrický liekmi navodený intertriginózny a flexurálny exantém. Prípad bol z diferenciálne-diagnostického hľadiska komplikovaný aj koexistenciou arteficiálne vzniknutého edému dolnej končatiny. Autori uvádzajú prehľad súčasných poznatkov o diagnostických a terapeutických možnostiach v manažmente tejto zriedkavej klinickej entity.
The authors describe a case of a 90-year-old patient with a rash that appeared a few hours after administration of amoxicillin clavulanate. Based on the presence of characteristic clinical features, a diagnosis of symmetrical drug- -related intertriginous and flexural exanthema was established. From the differential diagnosis point of view, the case was also complicated by the coexistence of artificially induced edema of the lower limb. The authors present an overview of current knowledge on diagnostic and therapeutic options in the management of this rare clinical entity.
- Klíčová slova
- SDRIFE,
- MeSH
- amoxicilin * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- antibakteriální látky aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- dolní končetina patologie MeSH
- edém MeSH
- exantém chemicky indukované farmakoterapie MeSH
- glukokortikoidy aplikace a dávkování terapeutické užití MeSH
- hemartróza terapie MeSH
- léková dermatitida * diagnóza etiologie patofyziologie MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- Publikační typ
- kazuistiky MeSH
Several studies have indicated the beneficial anti-inflammatory effect of butyrate in inflammatory bowel disease (IBD) therapy implying attempts to increase butyrate production in the gut through orally administered dietary supplementation. Through the gut-liver axis, however, butyrate may reach directly the liver and influence the drug-metabolizing ability of hepatic enzymes, and, indirectly, also the outcome of applied pharmacotherapy. The focus of our study was on the liver microsomal cytochrome P450 (CYP) 2A5, which is a mouse orthologue of human CYP2A6 responsible for metabolism of metronidazole, an antibiotic used to treat IBD. Our findings revealed that specific pathogen-free (SPF) and germ-free (GF) mice with dextran sulfate sodium (DSS)-induced colitis varied markedly in enzyme activity of CYP2A and responded differently to butyrate pre-treatment. A significant decrease (to 50%) of the CYP2A activity was observed in SPF mice with colitis; however, an administration of butyrate prior to DSS reversed this inhibition effect. This phenomenon was not observed in GF mice. The results highlight an important role of gut microbiota in the regulation of CYP2A under inflammatory conditions. Due to the role of CYP2A in metronidazole metabolism, this phenomenon may have an impact on the IBD therapy. Butyrate administration, hence, brings promising therapeutic potential for improving symptoms of gut inflammation; however, possible interactions with drug metabolism need to be further studied.
- MeSH
- antibakteriální látky škodlivé účinky farmakologie terapeutické užití MeSH
- antiflogistika farmakologie MeSH
- butyráty * farmakologie MeSH
- metronidazol farmakologie MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- síran dextranu škodlivé účinky MeSH
- střevní mikroflóra * MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- ulcerózní kolitida * chemicky indukované farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Jednou z častých příčin akutního poškození ledvin (AKI - acute kidney injury) je léková toxicita. Do široké skupiny léků spojených s AKI se řadí také velká část antimikrobiálních látek. Klinické projevy sahají od mírných forem tubulárního poškození až po významné zhoršení funkce ledvin vyžadující akutní náhradu jejich funkce. Z patogenetického hlediska se nejčastěji jedná o akutní intersticiální nefritidu, akutní tubulární nekrózu, krystalovou nefropatii či proximální/distální tubulopatii s abnormalitami v elektrolytovém hospodářství. Obecné rizikové faktory pro AKI vyvolané antimikrobiálními látkami zahrnují již existující chronické onemocnění ledvin a současné užívání léků s nefrotoxickým potenciálem. Prevence a včasné rozpoznání časných stadií poškození ledvin představují standardní přístup ke zmírnění progrese AKI a snížení morbidity.
One of the common causes of acute kidney injury (AKI) is drug nephrotoxicity. A large group of drugs associated with AKI includes a considerable number of antimicrobials. Clinical manifestations range from mild forms of tubular damage to significant deterioration of renal function requiring renal replacement therapy. Several mechanisms have been described, although the most common are acute interstitial nephritis, acute tubular necrosis, crystalic nephropathy or proximal/distal tubulopathy with electrolyte abnormalities. General risk factors for antimicrobial-induced AKI include pre-existing chronic kidney disease and concomitant use of drugs with nephrotoxic potential. Prevention and early recognition of AKI are the standard approach to mitigate AKI and avoid morbidity.
