An approach to the patient with positive history of penicillin allergy

Iako se ne zna točna učestalost alergije na lijekove, pripisuje joj se oko 1/10 svih neželjenih reakcija na lijekove. Neželjene reakcije na penicilin javljaju se u 0,7 – 10 % ljudi koji primaju penicilin. Stvarna učestalost alergije na penicilin još je manja, budući da su se u prošlosti mnoge nealergijske nuspojave antibiotika pripisivale alergiji. U pacijenata kod kojih postoji sumnja na alergiju na penicilin važno je utvrditi alergološki status. Nepotrebno izbjegavanje upotrebe penicilina, koji je jeftin i u većini slučajeva siguran lijek, povećava troškove bolničkog liječenja, morbiditet i mortalitet pacijenata. Suprotno, primjena penicilina u pacijenata koji su alergični na njega može dovesti do ozbiljnih neželjenih posljedica, uključujući i smrtni ishod. Kožni alergološki test najbrža je i optimalna metoda utvrđivanja alergije na penicilin. Provokacijski test penicilinom primjenjuje se u pacijenata s malom sumnjom na alergiju kod kojih su rezultati kožnog testa negativni uz anamnestičke neuvjerljive podatke za alergijsku reakciju. Liječenje antibiotikom različitog kemijskog sastava i mehanizma djelovanja ili desenzibilizacija moguće su terapijske opcije u pacijenata s dokazanom alergijom na penicilin. Desenzibilizacija je postupak kojim se izaziva privremena tolerancija na penicilin. Indikacije za primjenu su teška septička stanja uzrokovana bakterijama za koje ne postoji učinkovitiji lijek, a provodi se pod strogim nadzorom liječnika. Komercijalno dostupni alergološki dijagnostički testovi danas se smatraju sigurnim načinom utvrđivanja alergološkog statusa u pacijenata sa sumnjom na alergiju na penicilin.Although exact frequency of drug – induced allergic reactions is not known, they account for approximately 10 % of all adverse drug reactions. The frequency of some type of penicillin reactions in general population ranges between 0.7 % and 10 %. Actual incidence of penicillin allergy is even lower since in the past many non-allergic effects of antibiotic attributed to allergies. In suspected penicillin allergic patients, it is important to assess the allergological status. Inappropriate avoidance the use of penicillin, which is inexpensive and, in most cases, safe drug, increases the costs of hospitalization, morbidity and mortality of patients. In contrast, the use of penicillin in allergic patients can lead to serious adverse outcomes including death. The most efficient method of determining penicillin allergy is skin allergy test. Drug provocation testing is the most appropriate for a patient who is unlikely to be allergic to penicillin. This presupposition is based on the data of negative results of skin testing and not persuasive clinical history for penicillin allergy. Administration of an unrelated antibiotic or desensitization to penicillin are treatment options in patients prone to penicillin allergy. Desensitization is a procedure that encourages temporary tolerance to penicillin. It is treatment of choice in life – treating bacterial infection when there are no treatment alternatives and it need to be performed under close observation. Commercially available diagnostic tests are considered to be safe in detecting penicillin allergy in patients with suspected history for penicillin allergy

Variation in antibiotic use among and within different settings: a systematic review

Objectives: Variation in antibiotic use may reflect inappropriate use. We aimed to systematically describe the variation in measures for antibiotic use among settings or providers. This study was conducted as part of the innovative medicines initiative (IMI)-funded international project DRIVE-AB. Methods: We searched for studies published in MEDLINE from January 2004 to January 2015 reporting variation in measures for systemic antibiotic use (e.g. DDDs) in inpatient and outpatient settings. The ratio between a study's reported maximumand minimumvalues of a given measure [maximum: minimumratio (MMR)] was calculated as a measure of variation. Similar measures were grouped into categories and when possible the overall median ratio and IQR were calculated. Results: One hundred and forty-three studies were included, of which 85 (59.4%) were conducted in Europe and 12 (8.4%) in low-to middle-income countries. Most studies described the variation in the quantity of antibiotic use in the inpatient setting (81/143, 56.6%), especially among hospitals (41/81, 50.6%). Themost frequentmeasure was DDDs with different denominators, reported in 23/81 (28.4%) inpatient studies and in 28/62 (45.2%) outpatient studies. For this measure, we found a median MMR of 3.7 (IQR 2.6-5.0) in 4 studies reporting antibiotic use in ICUs in DDDs/1000 patient-days and a median MMR of 2.3 (IQR 1.5-3.2) in 18 studies reporting outpatient antibiotic use in DDDs/1000 inhabitant-days. Substantial variationwas also identified in othermeasures. Conclusions: Our review confirms the large variation in antibiotic use even across similar settings and providers. Data from low-and middle-income countries are under-represented. Further studies should try to better elucidate reasons for the observed variation to facilitate interventions that reduce unwarranted practice variation. In addition, the heterogeneity of reported measures clearly shows that there is need for standardization

Metrics to assess the quantity of antibiotic use in the outpatient setting: a systematic review followed by an international multidisciplinary consensus procedure

Background The international Innovative Medicines Initiative (IMI) project DRIVE-AB (Driving Reinvestment in Research and Development and Responsible Antibiotic Use) aims to develop a global definition of ‘responsible’ antibiotic use. Objectives To identify consensually validated quantity metrics for antibiotic use in the outpatient setting. Methods First, outpatient quantity metrics (OQMs) were identified by a systematic search of literature and web sites published until 12 December 2014. Identified OQMs were evaluated by a multidisciplinary, international stakeholder panel using a RAND-modified Delphi procedure. Two online questionnaires and a face-to-face meeting between them were conducted to assess OQM relevance for measuring the quantity of antibiotic use on a nine-point Likert scale, to add comments or to propose new metrics. Results A total of 597 articles were screened, 177 studies met criteria for full-text screening and 138 were finally included. Twenty different OQMs were identified and appraised by 23 stakeholders. During the first survey, 14 OQMs were excluded and 6 qualified for discussion. During the face-to-face meeting, 10 stakeholders retained five OQMs and suggestions were made considering context and combination of metrics. The final set of metrics included defined daily doses, treatments/courses and prescriptions per defined population, treatments/courses and prescriptions per defined number of physician contacts and seasonal variation of total antibiotic use. Conclusions A small set of consensually validated metrics to assess the quantity of antibiotic use in the outpatient setting was obtained, enabling (inter)national comparisons. The OQMs will help build a global conceptual framework for responsible antibiotic use

Quality indicators for responsible antibiotic use in the inpatient setting: a systematic review followed by an international multidisciplinary consensus procedure

Background This study was conducted as part of the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project and aimed to develop generic quality indicators (QIs) for responsible antibiotic use in the inpatient setting. Methods A RAND-modified Delphi method was applied. First, QIs were identified by a systematic review. A complementary search was performed on web sites of relevant organizations. Duplicates were removed and disease and patient-specific QIs were combined into generic indicators. The relevance of these QIs was appraised by a multidisciplinary international stakeholder panel through two questionnaires and an in-between consensus meeting. Results The systematic review retrieved 70 potential generic QIs. The QIs were appraised by 25 international stakeholders with diverse backgrounds (medical community, public health, patients, antibiotic research and development, regulators, governments). Ultimately, 51 QIs were selected in consensus. QIs with the highest relevance score included: (i) an antibiotic plan should be documented in the medical record at the start of the antibiotic treatment; (ii) the results of bacteriological susceptibility testing should be documented in the medical record; (iii) the local guidelines should correspond to the national guidelines but should be adapted based on local resistance patterns; (iv) an antibiotic stewardship programme should be in place at the healthcare facility; and (v) allergy status should be taken into account when antibiotics are prescribed. Conclusions This systematic and stepwise method combining evidence from literature and stakeholder opinion led to multidisciplinary international consensus on generic inpatient QIs that can be used globally to assess the quality of antibiotic use

Clindamycin-induced necrotising oesophagitis

A 43-year-old Caucasian female patient was admitted to the emergency department with chest pain and dysphagia for solids and liquids. Symptoms began after she took clindamycin 300 mg orally for one day and had been worsening for 24 h before she came to hospital. A constant, squeezing pain had started behind her breastbone, spreading to the upper stomach and back and was worsened by swallowing and movement. No nausea, vomiting, dyspnoea or fever was observed. Clindamycin had been prescribed as an antimicrobial prophylaxis before oral surgery (apicoectomy)

The impact of biological interventions on health-related quality of life in adults with Crohn's disease

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To systematically assess the beneficial and harmful effects of the biologic treatment on HRQoL outcomes in people with Crohn’s diseas

The multifactorial origin of posterior reversible encephalopathy syndrome in cyclophosphamide-treated lupus patients

The cyclophosphamide as a predisposing factor for Posterior Reversible Encephalopathy Syndrome (PRES) and therapeutic option for systemic lupus erythematosus (SLE) is still confusing. The first and only case of PRES, probably induced by cyclophosphamide, in Croatia followed by the findings of 36 SLE patients diagnosed with PRES after treatment with cyclophosphamide worldwide are described. An 18-year-old Caucasian female patient with a 1-year history of SLE was admitted to the hospital due to lupus nephritis and acute arthritis. After the second dose of cyclophosphamide was administered, according to the Euro-lupus protocol, the patient presented with a grand mal status epilepticus. The differential diagnosis of neurolupus, cerebrovascular insult, and infection were excluded. The MRI findings showed brain changes in corresponding to PRES. The treatment consisted of antihypertensives, antiepileptics, antiedema therapy, mechanical ventilation, and avoiding further cyclophosphamide use. A Naranjo Adverse Drug Reaction Probability Scale total score of five and a probable reaction related to drug therapy (cyclophosphamide, PRES) was confirmed. In this systematic review, along with cyclophosphamide use, the main predisposing factors involved in PRES occurrence in SLE patients were active SLE and renal involvement. Due to the high number of simultaneously involved predisposing factors (max. six) and their overlapping effect, it is still not possible to clearly establish the role of every factor on PRES onset. The use of cyclophosphamide, as a contributing factor for PRES onset, should be carefully assessed, based on clinicians' experience and knowledge, in the setting of active SLE

Repeated point prevalence survey on antimicrobial use in a university hospital: what have we learned?

Abstract Objectives To evaluate the quality of antimicrobial prescribing, at the Department of Internal Medicine University Hospital Centre Rijeka, by assessing the necessity for antimicrobial treatment and adherence to the local Guidelines for hospital antimicrobial drug use and to compare results with previously conducted point prevalence surveys (PPSs). Methods A PPS was conducted on 7th May 2019. Demographic and relevant clinical data of each patient receiving systemic antimicrobials were recorded anonymously in a patient-specific form. The appropriateness of antibiotic prescribing was assessed as adherence to the fourth edition of the Guidelines for hospital antimicrobial drug use. Key findings One hundred and seventy-one patients were hospitalized at the Department of Internal Medicine; 37.4% (n = 64) of patients received 102 prescriptions for an antimicrobial drug [62.8% (n = 64) of prescriptions were for intravenous and 37.2% (n = 38) for oral administration]. Of these, 52 were treated for an identified existing infection, 5 were treated for an unknown indication and 7 received antibiotics as prophylaxis. The necessity for antimicrobial treatment was unclear in 19.3% (n = 11) of cases. The antimicrobials were prescribed according to the Guidelines in 65.4% (n = 34) of cases. Adherence to the Guidelines when treating lower respiratory tract infections, urinary tract infections and gastrointestinal tract infections was 47.8%, 55.6% and 92.9%, respectively. Conclusions Our study revealed antibiotic prescription frequency similar to EU/EEA average and high percentage of unjustified antimicrobial treatment introduction. The rate of adherence to the Guidelines was lower than those observed in western countries.The results lay a basis for tailoring antimicrobial stewardship programs/activities

CYP2D6 *6/*6 genotype and drug interactions as cause of haloperidol induced extrapyramidal symptoms

A 66-year-old male Caucasian, received 1 mg of haloperidol orally and rapidly developed severe iatrogenic extrapyramidal symptoms. Treatment was immediately discontinued, and the side effects resolved. Haloperidol is mainly metabolized by Phase I CYP2D6 and to the lesser extent by CYP3A4 and by Phase II UGT2B7 enzymes. Genotyping was performed revealing CYP2D6*6/*6, CYP3A4*1/*1, and UGT2B7 -161 C/T genotypes, implicating poor, extensive and intermediate metabolism, respectively. Of the CYPs, haloperidol is metabolized by CYP2D6 and CYP3A4 primarily. It was the introduction of ciprofloxacin which was a trigger for the development of adverse drug reaction due to inhibition of CYP3A4, which was in presented patient main metabolic pathway for haloperidol since he was CYP2D6 poor metabolizer. Presented case report highlights the importance of genotyping. Pharmacogenetics testing should be considered when drug toxicity is suspected, polymorphic metabolic pathways used and drugs concomitantly applied