scholarly journals Cephalexin susceptibility breakpoint for veterinary isolates: Clinical Laboratory Standards Institute revision

2017 ◽  
Vol 30 (1) ◽  
pp. 113-120 ◽  
Author(s):  
Mark G. Papich ◽  
Cindy Lindeman
Keyword(s):  
First Generation ◽  
Clinical Laboratory ◽  
Surveillance Program ◽  
Pharmacokinetic Data ◽  
Penicillin Binding Protein ◽  
Target Attainment ◽  
Testing Susceptibility ◽  
Clinical Breakpoints ◽  
Class Representative ◽  
Susceptibility Breakpoint

The Clinical and Laboratory Standards Institute (CLSI) uses cephalothin as the class representative for testing veterinary isolates for susceptibility to other first-generation cephalosporins, including cephalexin. We examined replacing cephalothin with cephalexin because cephalexin is used more often clinically. Bacterial isolates were obtained from dogs and cats from a national surveillance program. CLSI testing methods were used to determine the MIC for 4 cephalosporins used in veterinary medicine. Cephalexin clinical breakpoints for canine isolates were established by using published pharmacokinetic data and Monte Carlo simulations to calculate the probability of target attainment (PTA). For 1,112 Staphylococcus pseudintermedius isolates, the mode, MIC50, and MIC90 were 1, 2, and 64 µg/mL, respectively, for cephalexin, and ≤0.06, 0.12, and 2 µg/mL for cephalothin. Susceptibility of S. pseudintermedius from 2011 to 2014 did not change for the 4 cephalosporins tested. Only 4.3% of the penicillin-binding protein 2a–positive S. pseudintermedius isolates had MIC values ≤2 µg/mL for cephalexin, but 66.3% of these isolates had MIC values ≤2 µg/mL for cephalothin. There were also discrepancies between cephalexin and cephalothin for other bacteria tested, but the largest difference was for S. pseudintermedius, with a MIC difference of 4 doubling dilutions. Cephalexin interpretive categories (breakpoints) of ≤2 μg/mL (susceptible), 4 μg/mL (intermediate), and ≥8 μg/mL (resistant) were established for isolates obtained from dogs. Cephalothin should not be used for susceptibility testing of cephalexin for veterinary bacterial pathogens, and canine-specific breakpoints should be used for testing susceptibility. Breakpoints determined using the methods described herein for the interpretive categories will be added to future CLSI tables to reflect this recommendation.

scholarly journals P42 External validation of model-based dosing guidelines for vancomycin, gentamicin and tobramycin in critically ill children

2019 ◽  
Vol 104 (6) ◽  
pp. e34.2-e34
Author(s):  
S Hartman ◽  
S Zwaag ◽  
L Orriëns ◽  
T Poel ◽  
M de Hoop - Sommen ◽  
...  
Keyword(s):  
Critically Ill ◽  
Clinical Laboratory ◽  
External Validation ◽  
Interindividual Variation ◽  
Critically Ill Children ◽  
Target Range ◽  
Future Research ◽  
Target Attainment ◽  
Model Based ◽  
Trough Concentrations

BackgroundPharmacokinetic models are frequently used to simulate dosing strategies for special populations, including critically ill children. The Dutch Pediatric Formulary (DPF) partially bases its guidelines on these models. However, prospective validation of updated dosing regimens is rare. We aimed to identify target attainment and safety of vancomycin, gentamicin and tobramycin after a dose update in the DPF for critically ill neonates and children.MethodsRetropsective cohort study in PICU and NICU patients receiving vancomycin, gentamicin or tobramycin between January 2015 and March 2017 in 2 university hospitals. Demographic clinical laboratory and TDM-data were collected. Target (steady state) trough concentrations for vancomycin, gentamicin and tobramycin used were 10–15, ≤1 and ≤1 mg/l, respectively. Target gentamicin peak concentrations used were 8–12 mg/l.Results486 patients were included in total (165 vancomycin, 97 gentamicin and 224 tobramycin). Trough concentrations of vancomycin, gentamicin and tobramycin were within the target range in 37.5%, 85.3% and 77.2% of patients, respectively. Target attainment of gentamicin peak concentrations in NICU patients was 31%. Non-target trough concentrations were most prevalent in term NICU patients (vancomycin 70%, gentamicin 26% and tobramycin 36.8%). Gentamicin peak concentrations were subtherapeutic in 91% and 45.5% for term and preterm NICU patients, respectively. Creatinine concentrations correlated positively with antibiotic concentrations (correlation coefficient range 0.46–0.54, p≤0.01 in all cohorts).ConclusionDespite recent model-based dosing alterations, sub- and supratherapeutic concentrations of vancomycin, gentamicin and tobramycin are still frequent in critically ill children. Linear dose alterations did offer improvements in target attainment, but did not fully address all relevant covariates that contribute to the large interindividual variation in clearance and/or volume of distribution in these patients. Creatinine clearance was consistently correlated with concentrations of all 3 drugs, but future research is needed to identify whether including this parameter in dosing can improve target attainment and safety.Disclosure(s)Nothing to disclose

scholarly journals PSVI-25 Antimicrobial resistance profiles of Pasteurella multocida, Mannheimia haemolytica and Moraxella spp. of bovine origin pre- and post- treatment with antimicrobials in calves

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 212-212
Author(s):  
Lourdes Migura-Garcia ◽  
Sonia Marti ◽  
Anna Aris ◽  
Ana Perez de Rozas ◽  
Carolina Tejero ◽  
...  
Keyword(s):  
Pasteurella Multocida ◽  
Bronchoalveolar Lavage Fluid ◽  
Clinical Laboratory ◽  
Lavage Fluid ◽  
Mannheimia Haemolytica ◽  
Resistant Bacteria ◽  
Respiratory Pathogens ◽  
Resistant Species ◽  
Current Production ◽  
Clinical Breakpoints

Abstract The current production system involves movement of calves combined with mixing animals, favouring the transmission of respiratory pathogens and increasing the risk of using antimicrobials. The aim of the study was to determine the presence and resistant profiles of Pasteurella multocida, Mannheimia haemolytica and Moraxella in the lungs of calves at arrival to the farm and after treatment with tulathromycin and florfenicol. Thoracic ultrasonography was performed in two batches of calves (n = 65 and 120, age=26±11.0, weight=45-55kg) at arrival, to select 27 calves/batch with lesions from low to severe. Bronchoalveolar lavage fluid (BALF) was collected on arrival (D0), D20 and D34, and also on D7 for the second batch. Pasteurella, Mannheimia and Moraxella were identified by VITEK. Detection of Mycoplasma bovis was performed by PCR. Minimal inhibitory concentration (MIC) was determined for 18 antimicrobials. Clinical breakpoints were defined by Clinical Laboratory Standards Institute. ERIC-PCR was performed in all isolates to assess similarities. Time effect was analysed by MIXED Procedure (SAS). At D0, 16 out of 54 BALFs contained P. multocida (n = 11), M. haemolytica (n = 5) and Moraxella (n = 4). The number of calves positive for primary pathogens decreased (P < 0.001) at D7 and D20, whereas by D34 positive animals leapt up to 21. MIC results demonstrated that P. multocida and M. haemolytica obtained at D0 were pansusceptible. Isolates of P. multocida collected after treatment, exhibited resistance to oxytetracycline, tilmicosin, tulathromycin, danofloxacin and enrofloxacin. ERIC-PCR demonstrated similar profiles of P. multocida and Moraxellain the two batches of calves after D7. Primary pathogens were susceptible to the initial treatment, however M. bovis was detected in all animals after D7. Resistant species appeared to recolonize the lungs after D34. ERIC-profile demonstrated that isolates recovered after treatment were different from those colonizing the lungs at arrival, suggesting recirculation of resistant bacteria between batches.

scholarly journals Twenty Years of the SENTRY Antifungal Surveillance Program: Results for Candida Species From 1997–2016

2019 ◽  
Vol 6 (Supplement_1) ◽  
pp. S79-S94 ◽  
Author(s):  
Michael A Pfaller ◽  
Daniel J Diekema ◽  
John D Turnidge ◽  
Mariana Castanheira ◽  
Ronald N Jones
Keyword(s):  
Candida Glabrata ◽  
Hot Spot ◽  
Bloodstream Infections ◽  
The United States ◽  
Asia Pacific ◽  
Steady Increase ◽  
Surveillance Program ◽  
Candida Auris ◽  
Medical Centers ◽  
Clinical Breakpoints

AbstractBackgroundThe emergence of antifungal resistance threatens effective treatment of invasive fungal infection (IFI). Invasive candidiasis is the most common health care–associated IFI. We evaluated the activity of fluconazole (FLU) against 20 788 invasive isolates of Candida (37 species) collected from 135 medical centers in 39 countries (1997–2016). The activity of anidulafungin, caspofungin, and micafungin (MCF) was evaluated against 15 308 isolates worldwide (2006–2016).MethodsSpecies identification was accomplished using phenotypic (1997–2001), genotypic, and proteomic methods (2006–2016). All isolates were tested using reference methods and clinical breakpoints published in the Clinical and Laboratory Standards Institute documents.ResultsA decrease in the isolation of Candida albicans and an increase in the isolation of Candida glabrata and Candida parapsilosis were observed over time. Candida glabrata was the most common non–C. albicans species detected in all geographic regions except for Latin America, where C. parapsilosis and Candida tropicalis were more common. Six Candida auris isolates were detected: 1 each in 2009, 2013, 2014, and 2015 and 2 in 2016; all were from nosocomial bloodstream infections and were FLU-resistant (R). The highest rates of FLU-R isolates were seen in C. glabrata from North America (NA; 10.6%) and in C. tropicalis from the Asia-Pacific region (9.2%). A steady increase in isolation of C. glabrata and resistance to FLU was detected over 20 years in the United States. Echinocandin-R (EC-R) ranged from 3.5% for C. glabrata to 0.1% for C. albicans and C. parapsilosis. Resistance to MCF was highest among C. glabrata (2.8%) and C. tropicalis (1.3%) from NA. Mutations on FKS hot spot (HS) regions were detected among 70 EC-R isolates (51/70 were C. glabrata). Most isolates harboring FKS HS mutations were resistant to 2 or more ECs.ConclusionsEC-R and FLU-R remain uncommon among contemporary Candida isolates; however, a slow and steady emergence of resistance to both antifungal classes was observed in C. glabrata and C. tropicalis isolates.

scholarly journals Minimum Inhibitory Concentration Breakpoints and Disk Diffusion Inhibitory Zone Interpretive Criteria for Tilmicosin Susceptibility Testing against Pasteurella Spp. Associated with Bovine Respiratory Disease

1996 ◽  
Vol 8 (3) ◽  
pp. 337-344 ◽  
Author(s):  
Thomas R. Shryock ◽  
Donald W. White ◽  
J. Mitchell Staples ◽  
Carolyn S. Werner
Keyword(s):  
Respiratory Disease ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Bovine Respiratory Disease ◽  
Disk Diffusion ◽  
National Committee ◽  
Pharmacokinetic Data ◽  
In Vitro Test ◽  
Disk Diffusion Testing

Tilmicosin is a novel macrolide antibiotic developed for exclusive use in veterinary medicine. The first tilmicosin-containing product was approved to treat bovine respiratory disease associated with pasteurellae. The development of antimicrobial susceptibility testing guidelines for tilmicosin was predicated on the relationship of clinical efficacy studies that demonstrated a favorable therapeutic outcome, on pharmacokinetic data, and on in vitro test data, as recommended by the National Committee for Clinical Laboratory Standards (NCCLS). The NCCLS-approved breakpoints for the MIC dilution testing are resistant ‡ 32 g/ml, intermediate 16 g/ml, and susceptible £ 8 g/ml. The zone of inhibition interpretive criteria for disk diffusion testing with a 15- g disk are resistant £ 10 mm, intermediate 11–13 mm, and susceptible ‡ 14 mm.

CANCER Resistance Surveillance Program: Initial Results from Hematology–Oncology Centers in North America

2003 ◽  
Vol 37 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Alan H Mutnick ◽  
Jeffrey T Kirby ◽  
Ronald N Jones ◽  
Keyword(s):  
North America ◽  
Clinical Laboratory ◽  
National Committee ◽  
Surveillance Program ◽  
Cancer Resistance ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Cutaneous Infections ◽  
Cancer Program ◽  
Klebsiella Spp

OBJECTIVE The CANCER (Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance) surveillance program was initiated to collect culture data on antimicrobial and antifungal agents in hospitals treating neutropenic patients in North America, as a means to monitor the development of microbial resistance. METHODS A total of 2042 isolates from bloodstream, respiratory, urinary, and cutaneous infections in 2000–2001 were submitted by 33 oncology centers, clinics, and hospitals in North America, sent to a central laboratory, and tested by National Committee for Clinical Laboratory Standards methods against 42 different antimicrobials. RESULTS Staphylococcus aureus, Escherichia coli, coagulase-negative staphylococci, Enterococcus spp., and Klebsiella spp. represented the most frequently isolated pathogens during the initial benchmark year. The incidence of extended-spectrum β-lactamase–producing phenotypes ranged from 1.6% to 4.6% among E. coli and Klebsiella spp. Amikacin, tobramycin, polymyxin B, and piperacillin/tazobactam provided the highest susceptibility rates against Pseudomonas aeruginosa isolates. Yeast bloodstream isolates demonstrated complete susceptibility to amphotericin B, but 14% of strains were considered to have high-level fluconazole resistance. CONCLUSIONS Elevated resistance rates when compared to general hospital strains were not observed in the CANCER program during the baseline year of this novel longitudinal, resistance surveillance program. The prevalence of gram-positive pathogens, although representing more than 50% of all bacterial isolates, was slightly lower than that reported previously by other investigators. Continued evaluation for antimicrobial resistance as well as changes in the prevalence of gram-positive pathogens requires the use of longitudinal surveillance programs such as the CANCER program. Such initiatives allow the development of therapeutic strategies for coping with changes in resistance and pathogen prevalence in this dynamic at-risk patient environment.

scholarly journals Activity of Ceftolozane-Tazobactam and Comparators When Tested against Bacterial Surveillance Isolates Collected from Pediatric Patients in the US during 2012–2016 as Part of a Global Surveillance Program

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S367-S367
Author(s):  
Dee Shortridge ◽  
Leonard R Duncan ◽  
Michael a Pfaller ◽  
Robert K Flamm
Keyword(s):  
Urinary Tract ◽  
Pediatric Patients ◽  
Infection Type ◽  
Common Species ◽  
Surveillance Program ◽  
Broth Microdilution Method ◽  
The Us ◽  
Clinical Breakpoints ◽  
Tract Infections ◽  
Research Grant

Abstract Background Ceftolozane-tazobactam (C-T) is an antibacterial combination of a novel antipseudomonal cephalosporin and a β-lactamase inhibitor. C-T was approved by the US Food and Drug Administration in 2014 and by the European Medicine Agency in 2015 to treat complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections in adults. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors C-T resistance to gram-negative (GN) isolates worldwide. Methods A total of 4121 GN isolates were collected during 2012–2016 from pediatric patients (<18 years old) in 31 US hospitals and tested for C-T susceptibility (S) by CLSI broth microdilution method in a central monitoring laboratory (JMI Laboratories). Other antibiotics tested were amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), colistin (COL), levofloxacin (LVX), meropenem (MER), and piperacillin-tazobactam (TZP). Antibiotic-resistant phenotypes identified using CLSI (2017) clinical breakpoints included: carbapenem-resistant Enterobacteriaceae (CRE), non-CRE extended-spectrum β-lactamase screen positive (ESBL, non-CRE), ceftazidime-nonsusceptible (CAZ-NS), and meropenem-NS (MER-NS). EUCAST (2017) COL clinical breakpoints were used for Enterobacteriaceae (ENT). Results The most common infection type in hospitalized pediatric patients was pneumonia (n = 1,488) followed by urinary tract infection (n = 1,143) and bloodstream infection (n = 767). A total of 2,969 ENT and 1,152 non-enterics were isolated. The 5 most common species were Escherichia coli (EC: 1,311), Pseudomonas aeruginosa (PSA: 821 isolates), Klebsiella pneumoniae (KPN: 429), Enterobacter cloacae complex (ECC: 360), and Serratia marcescens (SM: 264). Susceptibilities of C-T and comparators for the main species and resistant phenotypes are shown in the Table. Only 7 isolates were CRE in this study. Conclusion C-T demonstrated good activity against pediatric ENT isolates (96.1%S), EC (99.2%S), and KPN (97.9%S). For ENT, all agents but COL had >90% S. For PSA, C-T demonstrated potent activity (99.5%S) and was the most potent antibiotic tested with activity similar to COL. Disclosures D. Shortridge, Merck: Research Contractor, Research grant; L. R. Duncan, Merck: Research Contractor, Research grant; M. A. Pfaller, Merck: Research Contractor, Research grant; R. K. Flamm, Merck: Research Contractor, Research grant

scholarly journals Population Pharmacokinetics and Pharmacodynamics of Ofloxacin in South African Patients with Multidrug-Resistant Tuberculosis

2012 ◽  
Vol 56 (7) ◽  
pp. 3857-3863 ◽  
Author(s):  
Emmanuel Chigutsa ◽  
Sandra Meredith ◽  
Lubbe Wiesner ◽  
Nesri Padayatchi ◽  
Joe Harding ◽  
...  
Keyword(s):  
South Africa ◽  
Population Pharmacokinetics ◽  
South African ◽  
Multidrug Resistant ◽  
Pharmacokinetic Data ◽  
Target Attainment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Study Population ◽  
African Patients

ABSTRACTDespite the important role of fluoroquinolones and the predominant use of ofloxacin for treating multidrug-resistant tuberculosis in South Africa, there are limited data on ofloxacin pharmacokinetics in patients with multidrug-resistant tuberculosis, no ofloxacin pharmacokinetic data from South African patients, and no direct assessment of the relationship between ofloxacin pharmacokinetics and the MIC of ofloxacin of patient isolates. Our objectives are to describe ofloxacin pharmacokinetics in South African patients being treated for multidrug-resistant tuberculosis and assess the adequacy of ofloxacin drug exposure with respect to the probability of pharmacodynamic target attainment (area under the time curve/MIC ratio of at least 100). Sixty-five patients with multidrug-resistant tuberculosis were recruited from 2 hospitals in South Africa. We determined the ofloxacin MICs for theMycobacterium tuberculosisisolates from baseline sputum specimens. Patients received daily doses of 800 mg ofloxacin, in addition to other antitubercular drugs. Patients underwent pharmacokinetic sampling at steady state. NONMEM was used for data analysis. The population pharmacokinetics of ofloxacin in this study has been adequately described. The probability of target attainment expectation in the study population was 0.45. Doubling the dose to 1,600 mg could increase this to only 0.77. The currently recommended ofloxacin dose appeared inadequate for the majority of this study population. Studies to assess the tolerability of higher doses are warranted. Alternatively, ofloxacin should be replaced with more potent fluoroquinolones.

scholarly journals Molecular Characterization of Penicillin-Resistant Streptococcus pneumoniae Isolates from Bulgaria

1999 ◽  
Vol 37 (3) ◽  
pp. 638-648 ◽  
Author(s):  
Lena Setchanova ◽  
Alexander Tomasz
Keyword(s):  
Streptococcus Pneumoniae ◽  
Surveillance Program ◽  
Penicillin Binding Protein ◽  
Antibiotic Resistant ◽  
Length Polymorphisms ◽  
Unique Restriction ◽  
Resistant Strains ◽  
Ongoing Surveillance ◽  
Large Clusters

As part of an ongoing surveillance program of antibiotic-resistantStreptococcus pneumoniae in Sofia, Bulgaria, 120 penicillin-resistant strains (PRSP) (most of them recovered from children hospitalized with pneumococcal disease) were analyzed by microbiological and molecular methods. Several unique features of this collection are of particular interest. (i) Most isolates (112 of 120) were also resistant to trimethoprim-sulfamethoxazole (SXT) (97 of 120 isolates, or 80%), and over 70% (86 of 120) of the isolates were resistant to at least three antibiotics in addition to penicillin. (ii) Close to 80% of all isolates were represented by large clusters of bacteria, each with a unique serotype, antibiotype, and chromosomal macrorestriction pattern (determined by pulsed-field gel electrophoresis), as well as unique restriction fragmentation length polymorphisms of the penicillin-binding protein genespbp1a, pbp2x, and pbp2b. (iii) A large proportion (45 of 120, or 38%) of the strains belonged to two internationally spread epidemic clones of S. pneumoniae, the first expressing capsular type 23F and the second expressing serotype 9. (iv) A unique Bulgarian cluster composed of eight serotype 19F isolates was resistant to tetracycline, SXT, cefotaxime, and extremely high levels of penicillin and erythromycin. Nevertheless, this clone did not react with either the erm or the mef DNA probes, and thus the mechanism of macrolide resistance in this group of PRSP remains to be elucidated.

scholarly journals Haemophilus influenzae with Non-Beta-Lactamase-Mediated Beta-Lactam Resistance: Easy To Find but Hard To Categorize

2015 ◽  
Vol 53 (11) ◽  
pp. 3589-3595 ◽  
Author(s):  
Dagfinn Skaare ◽  
Astrid Lia ◽  
Anja Hannisdal ◽  
Yngvar Tveten ◽  
Erika Matuschek ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Disk Diffusion ◽  
High Dose ◽  
Beta Lactamase ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Content Type ◽  
Severe Infections ◽  
Clinical Breakpoints

Haemophilus influenzaeis a major pathogen, and beta-lactams are first-line drugs. Resistance due to altered penicillin-binding protein 3 (rPBP3) is frequent, and susceptibility testing of such strains is challenging. A collection of 154 beta-lactamase-negative isolates with a large proportion of rPBP3 (67.5%) was used to evaluate and compare Etest (Haemophilustest medium [HTM]) and disk diffusion (EUCAST method) for categorization of susceptibility to aminopenicillins and cefuroxime, using MICs generated with broth (HTM) microdilution and clinical breakpoints from CLSI and EUCAST as the gold standards. In addition, the proficiency of nine disks in screening for the rPBP3 genotype (N526K positive) was evaluated. By Etest, both essential and categorical agreement were generally poor (<70%), with high very major errors (VME) (CLSI, 13.0%; EUCAST, 34.3%) and falsely susceptible rates (FSR) (CLSI, 87.0%; EUCAST, 88.3%) for ampicillin. Ampicillin (2 μg) with adjusted (+2 mm) zone breakpoints was superior to Etest for categorization of susceptibility to ampicillin (agreement, 74.0%; VME, 11.0%; FSR, 28.3%). Conversely, Etest was superior to 30 μg cefuroxime for categorization of susceptibility to cefuroxime (agreement, 57.1% versus 60.4%; VME, 2.6% versus 9.7%; FSR, 7.1% versus 26.8%). Benzylpenicillin (1 unit) (EUCAST screening disk) and cefuroxime (5 μg) identified rPBP3 isolates with highest accuracies (95.5% and 92.2%, respectively). In conclusion, disk screening reliably detects rPBP3H. influenzae, but false ampicillin susceptibility is frequent with routine methods. We suggest adding a comment recommending high-dose aminopenicillin therapy or the use of other agents for severe infections with screening-positive isolates that are susceptible to aminopenicillins by gradient or disk diffusion.

scholarly journals Cardiovascular Adverse Reactions During Antipsychotic Treatment: Results of AMSP, A Drug Surveillance Program Between 1993 and 2013

2019 ◽  
Vol 23 (2) ◽  
pp. 67-75 ◽  
Author(s):  
Michaela-Elena Friedrich ◽  
Dietmar Winkler ◽  
Anastasios Konstantinidis ◽  
Wolfgang Huf ◽  
Rolf Engel ◽  
...  
Keyword(s):  
First Generation ◽  
Adverse Reactions ◽  
Second Generation ◽  
Antipsychotic Agents ◽  
Surveillance Program ◽  
Antipsychotic Treatment ◽  
Drug Surveillance ◽  
Cardiovascular Side Effects ◽  
Second Generation Antipsychotics ◽  
The Given

Abstract Background Cardiovascular diseases are still the leading cause of global mortality. Some antipsychotic agents can show severe cardiovascular side effects and are also associated with metabolic syndrome. Methods This observational study was based on data of AMSP (Arzneimittelsicherheit in der Psychiatrie), a multicenter drug surveillance program in Austria, Germany and Switzerland, that recorded severe drug reactions in psychiatric inpatients. Results A total of 404 009 inpatients were monitored between 1993 and 2013, whereas 291 510 were treated with antipsychotics either in combination or alone. There were 376 cases of severe cardiovascular adverse reactions reported in the given timespan, yielding a relative frequency of 0.13%. The study revealed that incidence rates of cardiovascular adverse reactions were highest during treatment with ziprasidone (0.35%), prothipendyl (0.32%), and clozapine (0.23%). The lowest rate of cardiovascular symptoms occurred during treatment with promethazine (0.03%) as well as with aripiprazole (0.06%). The most common clinical symptoms were orthostatic collapse and severe hypotonia, sinustachycardia, QTc prolongation, myocarditis, and different forms of arrhythmia. The dosage at the timepoint when severe cardiovascular events occurred was not higher in any of the given antipsychotics than in everyday clinical practice and was in average therapeutic ranges. In terms of subclasses of antipsychotics, no significant statistical difference was seen in the overall frequencies of adverse reactions cases, when first-generation high potency, first-generation low potency, and second-generation antipsychotics were compared. Thirty percent of adverse events among second-generation antipsychotics were induced by clozapine. Conclusions Our findings on cardiovascular adverse reactions contribute to a better understanding of cardiovascular risk profiles of antipsychotic agents in inpatients.

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