The role of routine SARS-CoV-2 screening of healthcare-workers in acute care hospitals in 2020: a systematic review and meta-analysis.

BACKGROUND: Healthcare workers (HCW) are at increased risk of infection with SARS-CoV-2. Vulnerable patient populations in particular must be protected, and clinics should not become transmission hotspots to avoid delaying medical treatments independent of COVID. Because asymptomatic transmission has been described, routine screening of asymptomatic HCW would potentially be able to interrupt chains of infection through early detection. METHODS: A systematic search was conducted in the Cochrane COVID-19 Study Register, Web of Science and WHO COVID-19 Global literature on coronavirus with regard to non-incident related testing of healthcare workers using polymerase chain reaction on May 4th 2021. Studies since January 2020 were included. An assessment of risk of bias and representativeness was performed. RESULTS: The search identified 39 studies with heterogeneous designs. Data collection of the included studies took place from January to August 2020. The studies were conducted worldwide and the sample size of the included HCW ranged from 70 to 9449 participants. In total, 1000 of 51,700 (1.9%) asymptomatic HCW were tested positive for SARS-CoV-2 using PCR testing. The proportion of positive test results ranged between 0 and 14.3%. No study reported on HCW-screening related reductions in infected person-days. DISCUSSION AND CONCLUSIONS: The heterogeneous proportions might be explained by different regional incidences, lock-downs, and pre-analytical pitfalls that reduce the sensitivity of the nasopharyngeal swab. The very high prevalence in some studies indicates that screening HCW for SARS-CoV-2 may be important particularly in geographical regions and pandemic periods with a high-incidence. With low numbers and an increasing rate of vaccinated HCW, a strict cost-benefit consideration must be made, especially in times of low incidences. Since we found no studies that reported on HCW-screening related reductions in infected person-days, re-evaluation should be done when these are available.

Comparative analyses of estimated and calorimetrically determined energy balance in high-yielding dairy cows.

Our aim was to compare the energy balance estimated (EBest) according to equations published by various energy feeding systems (German Society for Nutrition Physiology, French National Institute for Agricultural Research, and US National Research Council) and the EB calculated by use of calorimetrically measured heat production (EBhp) of 20 high-yielding (≥10,000 kg/305 d) German Holstein cows at -4 (pregnant, nonlactating) and 2 wk (early lactation) relative to parturition. In addition to heat production, feed and water intake, physical activity (including standing-lying behavior), body weight, body condition score, body temperature, plasma concentrations of fatty acids and ß-hydroxybutyrate, milk yield, and milk composition were measured to characterize the metabolic status. The EBhp was balanced [2.74 ± 4.09 MJ of metabolizable energy (ME)/d; ±standard error] before calving, but strongly negative (-84.7 ± 7.48 MJ of ME/d) at wk 2 of lactation. At both time points, EBhp and EBest differed significantly. On average, the equations overestimated the antepartum EB by 33 MJ of ME/d and underestimated the postpartum negative EB by 67 MJ of ME/d, respectively. Because the same ME intake and energy-corrected milk values were used for calculation of EBest and EBhp in our study, we considered that the factors (0.488 to 0.534 MJ of ME/kg0.75) currently used to calculate the ME requirements for maintenance probably underestimate the needs of high-yielding dairy cows, particularly during early lactation. In accord, heat production values determined under standard conditions of thermoneutrality and locomotion restriction amounted to 0.76 ± 0.02 MJ of ME/kg0.75 (4 wk antepartum) and 1.02 ± 0.02 MJ of ME/kg0.75 (2 wk postpartum), respectively. The expected positive correlation between EBhp and DMI was observed in pregnant cows only; however, a bias of 26 MJ of ME/d between mean actual energy intake and ME intake predicted according to German Society for Nutrition Physiology was found in cows at wk 4 antepartum. At both investigated time points, mobilization of tissue energy reserves (reflected by plasma fatty acid concentration) was related to EBhp. In early lactating cows, metabolic body weight (kg0.75) and the percentage of milk fat showed the strongest correlation (correlation coefficient = -0.70 and -0.73) to EBhp. Our findings must be taken into account when experimental data are interpreted because the true energy status might be significantly overestimated when EBest is used.

Seismic imaging and petrology explain highly explosive eruptions of Merapi Volcano, Indonesia.

Our seismic tomographic images characterize, for the first time, spatial and volumetric details of the subvertical magma plumbing system of Merapi Volcano. We present P- and S-wave arrival time data, which were collected in a dense seismic network, known as DOMERAPI, installed around the volcano for 18 months. The P- and S-wave arrival time data with similar path coverage reveal a high Vp/Vs structure extending from a depth of ≥20 km below mean sea level (MSL) up to the summit of the volcano. Combined with results of petrological studies, our seismic tomography data allow us to propose: (1) the existence of a shallow zone of intense fluid percolation, directly below the summit of the volcano; (2) a main, pre-eruptive magma reservoir at ≥ 10 to 20 km below MSL that is orders of magnitude larger than erupted magma volumes; (3) a deep magma reservoir at MOHO depth which supplies the main reservoir; and (4) an extensive, subvertical fluid-magma-transfer zone from the mantle to the surface. Such high-resolution spatial constraints on the volcano plumbing system as shown are an important advance in our ability to forecast and to mitigate the hazard potential of Merapi's future eruptions.

Indices of heart rate variability as potential early markers of metabolic stress and compromised regulatory capacity in dried-off high-yielding dairy cows.

High performing dairy cows experience distinct metabolic stress during periods of negative energy balance. Subclinical disorders of the cow's energy metabolism facilitate failure of adaptational responses resulting in health problems and reduced performance. The autonomic nervous system (ANS) with its sympathetic and parasympathetic branches plays a predominant role in adaption to inadequate energy and/or fuel availability and mediation of the stress response. Therefore, we hypothesize that indices of heart rate variability (HRV) that reflect ANS activity and sympatho-vagal balance could be early markers of metabolic stress, and possibly useful to predict cows with compromised regulatory capacity. In this study we analysed the autonomic regulation and stress level of 10 pregnant dried-off German Holstein cows before, during and after a 10-h fasting period by using a wide range of HRV parameters. In addition heat production (HP), energy balance, feed intake, rumen fermentative activity, physical activity, non-esterified fatty acids, ß-hydroxybutyric acid, cortisol and total ghrelin plasma concentrations, and body temperature (BT) were measured. In all cows fasting induced immediate regulatory adjustments including increased lipolysis (84%) and total ghrelin levels (179%), reduction of HP (-16%), standing time (-38%) and heart rate (-15%). However, by analysing frequency domain parameters of HRV (high-frequency (HF) and low-frequency (LF) components, ratio LF/HF) cows could be retrospectively assigned to groups reacting to food removal with increased or decreased activity of the parasympathetic branch of the ANS. Regression analysis reveals that under control conditions (feeding ad libitum) group differences were best predicted by the nonlinear domain HRV component Maxline (L MAX, R 2=0.76, threshold; TS=258). Compared with cows having L MAX values above TS (>L MAX: 348±17), those with L MAX values below TS (L MAX cows (18.5±0.4 and 47.3 kg/day). From the present study, it seems conceivable that L MAX can be used as a predictive marker to discover alterations in central autonomic regulation that might precede metabolic disturbances.

Variable liver fat concentration as a proxy for body fat mobilization postpartum has minor effects on insulin-induced changes in hepatic gene expression related to energy metabolism in dairy cows.

The liver plays a central role in adaptation for energy requirements around calving, and changes in the effects of insulin on hepatic energy metabolism contribute to metabolic adaptation in dairy cows. Hepatic insulin effects may depend on body fat mobilization. The objective of this study was to investigate the effects of insulin on the hepatic gene expression of enzymes involved in energy metabolism and factors related to nutrition partitioning in cows with high and low total liver fat concentration (LFC) after calving. Holstein cows were retrospectively grouped according to their LFC after calving as a proxy for body fat mobilization. Cows were classified as low (LLFC; LFC <24% fat/dry matter; n = 9) and high (HLFC; LFC >24.4% fat/dry matter; n = 10) fat-mobilizing after calving. Euglycemic-hyperinsulinemic clamps [6 mU/(kg × min) of insulin for 6 h] were performed in wk 5 antepartum (ap) and wk 3 postpartum (pp). Before and at the end of the euglycemic-hyperinsulinemic clamps, liver biopsies were taken to measure the mRNA abundance of enzymes involved in carbohydrate and lipid metabolism, expression related to the somatotropic axis, and adrenergic and glucocorticoid receptors. The mRNA abundance of pyruvate carboxylase, cytosolic phosphoenolpyruvate carboxykinase (PEPCK; PCK1), acyl-CoA-dehydrogenase very long chain (ACADVL), and hydroxyl-methyl-glutaryl-CoA-synthase 1 increased, but the mRNA abundance of solute carrier family 2 (SLC2A2 and SLC2A4), growth hormone receptor 1A (GHR1A), insulin-like growth factor 1 (IGF1), sterol regulatory element binding factor 1, adrenoceptor α 1A, and glucocorticoid receptor decreased from ap to pp. Insulin treatment was associated with decreased PCK1, mitochondrial PEPCK, glucose-6-phosphatase, propionyl-CoA-carboxylase α, carnitine-palmitoyl-transferase 1A, ACADVL, and insulin receptor mRNA, but increased IGF1 and SLC2A4 mRNA ap and pp and GHR1A mRNA pp. The mRNA abundance of SLC2A4 was greater, and the mRNA abundance of GHR1A and IGF1 tended to be lower in LLFC than in HLFC. Administration of insulin, albeit at a supraphysiological dose, was associated with inhibition of gene expression related to glucose production and ß-oxidation, but we observed variable effects in the degree of insulin depression of individual genes. Insulin status is important for regulation of nutrient partitioning, but different LFC pp had very little influence on changes in hepatic gene expression following administration of insulin.

Insulin-dependent glucose metabolism in dairy cows with variable fat mobilization around calving.

Dairy cows undergo significant metabolic and endocrine changes during the transition from pregnancy to lactation, and impaired insulin action influences nutrient partitioning toward the fetus and the mammary gland. Because impaired insulin action during transition is thought to be related to elevated body condition and body fat mobilization, we hypothesized that over-conditioned cows with excessive body fat mobilization around calving may have impaired insulin metabolism compared with cows with low fat mobilization. Nineteen dairy cows were grouped according to their average concentration of total liver fat (LFC) after calving in low [LLFC; LFC <24% total fat/dry matter (DM); n=9] and high (HLFC; LFC >24.4% total fat/DM; n=10) fat-mobilizing cows. Blood samples were taken from wk 7 antepartum (ap) to wk 5 postpartum (pp) to determine plasma concentrations of glucose, insulin, glucagon, and adiponectin. We applied euglycemic-hyperinsulinemic (EGHIC) and hyperglycemic clamps (HGC) in wk 5 ap and wk 3 pp to measure insulin responsiveness in peripheral tissue and pancreatic insulin secretion during the transition period. Before and during the pp EGHIC, [(13)C6] glucose was infused to determine the rate of glucose appearance (GlucRa) and glucose oxidation (GOx). Body condition, back fat thickness, and energy-corrected milk were greater, but energy balance was lower in HLFC than in LLFC. Plasma concentrations of glucose, insulin, glucagon, and adiponectin decreased at calving, and this was followed by an immediate increase of glucagon and adiponectin after calving. Insulin concentrations ap were higher in HLFC than in LLFC cows, but the EGHIC indicated no differences in peripheral insulin responsiveness among cows ap and pp. However, GlucRa and GOx:GlucRa during the pp EGHIC were greater in HLFC than in LLFC cows. During HGC, pancreatic insulin secretion was lower, but the glucose infusion rate was higher pp than ap in both groups. Plasma concentrations of nonesterified fatty acids decreased during HGC and EGHIC, but in both clamps, pp nonesterified fatty acid concentrations did not reach the ap levels. The study demonstrated a minor influence of different degrees of body fat mobilization on insulin metabolism in cows during the transition period. The distinct decrease in the glucose-dependent release of insulin pp is the most striking finding that explains the impaired insulin action after calving, but does not explain differences in body fat mobilization between HLFC and LLFC cows.

Pulmonary leiomyosarcoma mimicking glomus tumor at first biopsy and surgically treated with isolated left main bronchus resection: rare clinical documentation.

Soft tissue tumors originating within the endobronchial tree are extremely rare and most of them correspond to lipomas or leiomyomas. We here report a rare clinical presentation of leiomyosarcoma mimicking glomus tumor at initial biopsy arising from the left main bronchial trunk leading to left lower lobe atelectasis. Primary leiomyosarcoma of the lung is an unusual malignancy. Among this entity, the endobronchial form is very rare and the preoperative diagnosis is extremely difficult. We documented two different presentations and outcomes of primary endobronchial leiomyosarcoma of the lung. In this clinical presentation, histological study and immunohistochemical stain of the surgical resection provided the final diagnosis. Through the following we present the diagnostic and therapeutic difficulties encountered with endobronchial leiomyosarcoma.

Pleural mesothelioma presenting as periumbilical metastasis: the first clinical documentation.

Introduction. Pleural mesothelioma with metastasis to the subcutaneous tissue of the abdominal wall at first diagnosis and without penetration into the peritoneum is an extremely rare clinical presentation. Methods. Patients with pleural mesothelioma have low survival rate. Usually, the disease at presentation is confined to its site of origin (most often the pleural cavity). A 55-year-old man was referred to our center due to increasing dyspnea and a painful periumbilical mass in the anterior abdominal wall. CT scan revealed both advanced mesothelioma of the pleura and a tumor mass confined to the subcutaneous fatty tissue without penetration through the peritoneum. Results. Video-assisted thoracoscopy confirmed the diagnosis of epithelioid pleural mesothelioma, which was also confirmed by a biopsy of the periumbilical mass. Systemic chemotherapy with cisplatin and pemetrexed was initiated. Under the ongoing systemic chemotherapy, the evaluation revealed partial remission of pleura mesothelioma and its subcutaneous manifestation of the abdominal wall. Conclusion. Mesothelioma of the pleura with a simultaneous metastasis to the subcutaneous fatty tissue of the abdominal wall at presentation without penetration of peritoneum is a rare clinical presentation of mesothelioma disease. The knowledge of its natural history is very limited. This is the first ever clinical documentation of a patient with pleura mesothelioma and simultaneous subcutaneous manifestation of abdominal wall.

Late lung metastasis of a primary eccrine sweat gland carcinoma 10 years after initial surgical treatment: the first clinical documentation.

Background. Sweat gland carcinoma is a rare malignancy with a high metastatic potential seen more commonly in elderly patients. The scalp is the most common site of occurrence and it usually spreads to regional lymph nodes. Liver, lungs, and bones are the most common sites of distant metastasis. Late lung metastasis of sweat gland adenocarcinoma after a time span of 5 years is extremely rare. Aim. We report a patient with late lung metastasis of a primary sweat gland carcinoma 10 years after initial surgical resection. Conclusion. Sweat gland carcinomas are rare cancers with a poor prognosis. Surgery in the form of wide local excision and lymph node dissection is the mainstay of treatment. Late pulmonary metastases with a latency of 10 years have never been reported in the literature. This is the first clinical documentation of late lung metastasis from sweat gland carcinoma with a latency period of 10 years.

In vitro detection and characterization of drug hypersensitivity using flow cytometry.

BACKGROUND: The lymphocyte transformation test (LTT) is the only in vitro test for detecting drug sensitization at the cellular level irrespective of the reaction's phenotype. However, the LTT includes working with radioactive substances and is considered impracticable for routine laboratory investigation. OBJECTIVE: The aim of this study was to assess drug-specific cytokine production by means of flow cytometry as an alternative nonradioactive approach which may be more appropriate for routine testing and may provide in addition more information about the pathophysiology of the reaction than proliferation-based assays, like the LTT. METHOD: Peripheral blood mononuclear cells of 19 patients were incubated with culprit drugs (n = 28) or irrelevant antigens (n = 10). Ten healthy persons served as controls for all different drugs (n = 15). Intracellular interleukin (IL)-5, interferon (IFN)-gamma and IL-10 production was investigated using flow cytometry. Accuracy of the flow cytometry test system was confirmed using different statistical tests, i.e. receiver operating characteristic curve and Mann-Whitney rank test. In addition, drug-specific secretion of IL-5, IL-2 and IFN-gamma were analysed using enzyme-linked immunosorbent assay (ELISA). RESULTS: Drug-specific cytokine production could be demonstrated in 75% of the patients using flow cytometry and in 79% using ELISA respectively. Combining ELISA and flow cytometry increased the sensitivity to 100%. Analysis of involved T-cell subsets [e.g. CD4(+) or CD8(+); T helper (TH) 1 or TH 2] allowed characterization of the in vitro lymphocyte reactivity pattern. CONCLUSIONS: Analysis of drug-specific cytokine production by means of flow cytometry proved a useful and reliable approach for the in vitro detection and characterization of drug hypersensitivities.

Association between TNFA-308 G/A polymorphism and sensitization to para-phenylenediamine: a case-control study.

BACKGROUND: Para-phenylenediamine (PPD) and related chemicals are common contact sensitizers, frequently causing allergic contact dermatitis (ACD). The cytokine tumor necrosis factor-alpha (TNF-alpha) plays a key role in contact sensitization. METHODS: In this case-control study, we evaluated the distribution of variations in the regulatory region of the gene for TNF-alpha (TNFA-308 G/A) in 181 Caucasian individuals with a history of ACD and sensitization to PPD and 161 individuals with no history of sensitization to PPD. RESULTS: The frequency of GA or AA TNFA genotypes was significantly higher in individuals sensitized to PPD than in age- and gender-matched controls giving an odds ratio (OR) of 2.16 (95% confidence interval, CI: 1.35-3.47; P = 0.0016). This relation was even more pronounced when restricting cases to females over 45 years (OR = 3.71; 95% CI: 1.65-8.31; P = 0.0017) vs younger females (less than or equal to 45 years; OR = 2.41; 95% CI: 1.03-5.65; P = 0.044) or males (OR = 1.05; 95% CI: 0.449-2.47; P = 1.0). In addition, a logistic regression model revealed a significant effect for TNFA-308 AA and AG vs GG genotype (point estimate = 2.152; 95% Wald CI: 1.332-3.477). CONCLUSIONS: These findings suggest a possible role for the TNFA-308 genetic polymorphism as a susceptibility factor for chemically induced ACD.

Anaphylaxis and toxic epidermal necrolysis or Stevens-Johnson syndrome after nonmucosal topical drug application: fact or fiction?

BACKGROUND: Drug-induced anaphylaxis and toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome (SJS) represent severe immediate and delayed-type adverse drug reactions (ADRs), respectively. Occurrence of such reactions after topical drug application has only rarely been reported. Hence, we compiled a large number of such cases which we systematically analyzed. METHODS: All such cases contained in the ADR database of the competent pharmacovigilance authority in Germany and cases reported in literature were identified, evaluated and analyzed with regard to potential risk factors. Since the application of drugs to mucous membranes facilitates their entry to the systemic circulation only cases occurring after non-mucosal topical drug application were considered. RESULTS: After evaluation 28 anaphylaxis database cases and 48 anaphylaxis literature cases remained for analysis. Application to skin wounds or to skin with impaired barrier function was identified as a risk factor in 10/28 (36%) of the database cases and in 42/48 (88%) of the literature cases. In 9/28 database cases (32%), anaphylaxis was induced by drugs used for their hyperemizing effect and, in 8/28 cases (29%) by antibiotics or antiseptics. In the literature cases, anaphylaxis was induced by antibiotics or antiseptics in 35/48 cases (73%). Only one SJS database case and one TEN literature case remained after case evaluation. CONCLUSION: Anaphylaxis does occur after non-mucosal topical drug administration. Application of drugs to skin wounds or to skin with impaired barrier function may pose a risk factor for its occurrence. TEN or SJS following non-mucosal topical drug application seems to be extremely rare.

[Hematogenous contact eczema induced by foods]. / Hämatogene Kontaktekzeme durch Nahrungsmittel.

Oral ingestion or parenteral administration of certain contact allergens may elicit eczematous skin reactions "from inside" in sensitized individuals; this phenomenon has been termed "systemically-induced eczema" or "hematogenous contact eczema". There is a wide range of clinical features from polyetiological dyshidrotic hand and foot eczema to baboon syndrome. The most important contact allergens known to elicit systemically-induced contact eczema are metal salts, drugs, phytoallergens and balsam of Peru. Diagnosis is based on proof of delayed type hypersensitivity by patch testing and oral challenge. Until more and better data is acquired, special diets (for instance low nickel) should be instituted only in carefully selected patients.

In vitro analysis of birch-pollen-associated food allergy by use of recombinant allergens in the basophil activation test.

BACKGROUND: Basophil activation is associated with the expression of CD63. In birch-pollen-associated food allergy to celery, carrot and apple, Bet v 1, Api g 1, Dau c 1 and Mal d 1 are major allergens. Recombinant allergens have not yet been used in the CD63-based basophil activation test (BAT). OBJECTIVE: To evaluate the feasibility of using recombinant allergens in the BAT in the diagnosis of allergy to apple, carrot and celery and to compare results with routine tests, i.e. skin prick tests (SPTs) and specific IgE. METHODS: Thirty-two patients with an oral allergy syndrome induced by apple, carrot or celery and 22 controls were studied. SPTs were performed with native foods. Specific IgE was determined by the CAP method and basophil activation by flowcytometry upon double staining with anti-IgE/anti-CD63 monoclonal antibodies after incubating with purified recombinant Bet v 1, Bet v 2, Api g 1, Dau c 1 and Mal d 1. RESULTS: By the combined use of the BAT and the CAP method, sensitization to Bet v 1 and Bet v 2 was detected in 100 and 25% of all subjects, respectively. Sensitivity of specific IgE for apple, carrot and celery was 60, 70 and 75% with corresponding specificities of 64, 86 and 82%. Sensitivity of the BAT for Mal d 1, Dau c 1 and Api g 1 was 75, 65 and 75% with corresponding specificities of 68, 100 and 77%. CONCLUSIONS: The BAT using recombinant allergens provides a valuable new in vitro method for the detection of sensitization to foods. Although double-blind placebo-controlled food challenges remain the gold standard to confirm food allergy, the CD63-based BAT with recombinant allergens may supplement routine tests for allergy diagnosis.

Circulating clonal CLA(+) and CD4(+) T cells in Sezary syndrome express the skin-homing chemokine receptors CCR4 and CCR10 as well as the lymph node-homing chemokine receptor CCR7.

BACKGROUND: Adhesion molecules and chemokine receptors are involved in tissue-specific homing of T cells to the skin and play an important role in the pathophysiology of cutaneous lymphoma. It has recently been reported that the chemokine CCL27 expressed by keratinocytes attracts lymphocytes bearing the chemokine receptor CCR10. OBJECTIVES: To investigate the expression of CCR4, CCR7 and CCR10 on skin-homing CLA(+) and CD4(+) T cells in the peripheral blood of patients with Sezary syndrome (SS), a rare leukaemic variant of cutaneous T-cell lymphoma. METHODS: Lymphocytes from five patients with SS, six patients with mycosis fungoides and four healthy volunteers were isolated and analysed using flow cytometry. Additionally, the T-cell receptor (TCR)-Vbeta CDR3 regions were cloned and sequenced in two patients. RESULTS: We found that CCR4 is expressed on almost all CLA(+) and CD4(+) memory T cells. Using monoclonal antibodies specific for single TCR-Vbeta chains we identified malignant T cells in four patients with SS. Importantly, we found that most but not all malignant Sezary cells expressed the skin-homing chemokine receptor CCR10. Additionally, we found that a significant proportion of these cells also expressed the lymph node-homing chemokine receptor CCR7. CONCLUSIONS: Our results support the concept that chemokine receptors play an important role in the pathophysiology of SS and suggest that the malignant clone may represent an expansion of skin-homing cutaneous 'central' memory T cells in the peripheral blood of these patients.

[Basophil activation tests in the diagnosis of drug reactions]. / Basophilenaktivierungstests in der Diagnostik von Arzneimittelreaktionen.

Over the past 10 years a number of studies on basophil activation tests (BAT) have been published which focus on their use as diagnostic methods in clarifying IgE-mediated hypersensitivity reactions to various allergens including drugs. These BAT are based on flow cytometric quantification of allergen- induced CD63 or CD203 expression or measurement of sulfo leukotriene release by ELISA. In the diagnosis of penicillin allergy, the combined use of the CD63-BAT and specific IgE increases sensitivity. The role of BAT in the diagnosis of non-IgE-mediated reactions to non-steroidal anti- inflammatory drugs remains to be clarified. This article focuses on (1) the principles of BAT, (2) technical aspects, (3) clinical applications and (4) recommendations for further development.

Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs.

BACKGROUND: Amino-penicillins are a major cause of delayed-type reactions to penicillins. OBJECTIVES: The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. METHODS: We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. RESULTS: A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. CONCLUSIONS: These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.