Epidemiological trends in electronic cigarette exposures reported to U.S. Poison Centers

Context. The Centers for Disease Control and Prevention (CDC) has reported an increase in electronic cigarette (e-cigarette) use in both adults and adolescents. Poison Center calls provide data on exposures pertaining to e-cigarette devices and components (including nicotine-refill cartridges), potentially identifying epidemiological trends in reported exposures over time. Objective. To characterize the trends in e-cigarette exposures reported to United States (U.S.) Poison Centers between 01 June 2010 and 30 September 2013. Methods. We obtained data from the American Association of Poison Control Centers (AAPCC) for all exposures involving e-cigarettes reported to the National Poison Data System (NPDS) by U.S. Poison Centers and described trends in exposures over time, demographics, geographical characteristics, clinical effects and outcomes, management site, and exposure route. Results. A total of 1,700 exposures were reported to Poison Centers during this time. The most frequent age groups were children 5 years or below with 717 (42.2%) exposures and adults ages 20–39 years with 466 (27.4%) exposures. Temporal trends showed an increase of 1.36 exposures per month [95% CI: 1.16–1.56] from June 2010 through December 2012, after which exposures increased by 9.60 per month [95% CI: 8.64–10.55] from January through September 2013. The majority of patients who were followed reported that they had only minor effects. Conclusions. The majority of exposures to e-cigarette devices and components occurred in children of 5 years or below due to accidental exposure. Based on the available data, the reported exposures have resulted in minimal toxicity. Calls to Poison Centers regarding these products have rapidly increased since 2010, and continued surveillance may show changes in the epidemiological trends surrounding e-cigarette exposures.     

Human bromethalin exposures reported to a U.S. Statewide Poison Control System

Background: Bromethalin is an increasingly used alternative to long-acting anticoagulant and cholecalciferol rodenticides. There are few reports of human exposures, and no existing professional society guidelines on medical management of bromethalin ingestions. The aim of this retrospective data review is to characterize bromethalin exposures reported to the California Poison Control System (CPCS) between 1997 and 2014. Methods: This is an observational retrospective case review of our statewide poison control system’s electronic medical records. Following Institutional Board Review and Research Committee approvals, poison center exposures related to bromethalin were extracted using substance code and free text search strategies. Case notes of bromethalin exposures were reviewed for demographic, clinical, laboratory, and outcome information; inclusion criteria for the study was single-substance, human exposure to bromethalin. Results: There were 129 calls related to human bromethalin exposures (three cases met exclusion criteria). The age range of cases was 7 months–90 years old, with the majority of exposures (89 cases; 70.6%), occurring in children younger than 5 years of age (median age of 2 years). Most exposures occurred in the pediatric population as a result of exploratory oral exposure. One hundred and thirteen patients (89.7%) had no effects post exposure, while 10 patients (7.9%) had a minor outcome. Adverse effects were minor, self-limited, and mostly gastrointestinal upset. There were no moderate, major, or fatal effects in our study population. The approximate ingested dose, available in six cases, ranged from 0.067?mg/kg to 0.3?mg/kg (milligrams of bromethalin ingested per kilogram of body weight), and no dose-symptom threshold could be established from this series. Exposures were not confirmed through urine or serum laboratory testing. Discussion: The prognosis for most accidental ingestions appears to be excellent. However, bromethalin exposures may result in a higher number of symptomatic patients than long-acting anticoagulant agents. Parents, physicians and poison control specialists are encouraged to maintain a high index of suspicion for bromethalin-related complications in all cases of rodenticide exposures. Conclusions: Accidental bromethalin exposures in children appear to be self-limited in toxicity. Additional studies are warranted to determine whether more severe effects are precipitated when larger amounts are involved, particularly in suicidal ingestion.     

Calls to Poison Centers for hookah smoking exposures

Over the past decade, smoking behaviors have changed in the US. Hookah or waterpipe smoking is increasing, especially among youth and young adults. Social media sites describe the “hookah high” or “buzz”, which may be related to nicotine, carbon monoxide, or other inhalants in hookah smoke. Most important is the risk of carbon monoxide poisoning. Case reports include a high number of victims presenting with loss of consciousness from either syncope or seizures. Anaphylaxis and a very rare respiratory hypersensitivity reaction, acute eosinophilic pneumonia, have also been reported from hookah smoking in previously healthy young adults. This article provides background information on hookah smoking, describes hookah-induced acute injuries that could precipitate poison center calls, and offers suggestions for exposure characterization.     

Comparison of pediatric atypical antipsychotic exposures reported to U.S. poison centers

Context: The rise in atypical antipsychotic prescribing increases the risk of pediatric exposures. Published studies in children are limited.

Objective: The objectives are to evaluate national poison center data on atypical antipsychotic exposures in young children and compare toxicity amongst selected agents.

Materials and methods: A retrospective study of U.S. National Poison Data System single substance exposures, from 2005 to 2013, of five atypical antipsychotics in children <6 years old, followed to known outcome was performed. Data were evaluated for reason, clinical effects, management site and outcome.

Results: There were 16,935 exposures included: 5018 aripiprazole, 1735 olanzapine, 3904 quetiapine, 4778 risperidone and 1500 ziprasidone. Median age was two years. Most common reason was unintentional-general (90.6%). Therapeutic error occurred more often with risperidone (19.9%). Clinical effects occurred in 59.4% of aripiprazole, 57.9% of olanzapine, 56.6% of ziprasidone, 40.1% of risperidone, and 29.3% of quetiapine. The most frequent were drowsiness/lethargy (35.6%), tachycardia (6.9%), agitation (4.0%), and ataxia (3.3%). Drowsiness/lethargy occurred most with aripiprazole (47.6%), ziprasidone (46.5%) and olanzapine (45.1%) and least with quetiapine (20.5%) and risperidone (28.6%). Tachycardia and agitation both occurred most often with olanzapine (11.4% and 12.7%, respectively). Management sites were non-health care facility (28.0%), treated/discharged from emergency department (48.9%), admitted – noncritical care (11.4%), critical care (9.5%), and other/unknown (2.2%). Admission was lowest for risperidone (13.9%) and quetiapine (11.9%) and highest for olanzapine (32.9%). Coded outcomes were no effect (53.3%), minor (33.7%), moderate (12.1%), major (0.9%) and no deaths. Moderate/major outcomes occurred most often with ziprasidone (20.5%) and olanzapine (19.0%) and least often with quetiapine (5.3%) and risperidone (10.9%).

Discussion and conclusion: Overall outcomes were favorable, with major toxicity in <1% of exposures. Risperidone and quetiapine exposures resulted in less toxicity. This finding may be attributed to higher frequency of therapeutic errors for risperidone but the reason for less toxicity with quetiapine is unclear.     

Asenapine,iloperidone and lurasidone exposures in young children reported to U.S. poison centers

Context: Asenapine, iloperidone and lurasidone are relatively new atypical antipsychotics. There is limited information on toxicity on pediatric exposures to these drugs. The objective of this study was to compare toxicity associated with asenapine, iloperidone and lurasidone exposures in young children.

Methods: A retrospective study of U.S. National Poison Data System from 2010 to 2015 of single substance exposures to asenapine, iloperidone or lurasidone in children <6 years of age that were followed to known outcome was performed.

Results: There were 95 asenapine, 64 iloperidone and 124 lurasidone cases that met inclusion criteria. Reason was exploratory for 96% of cases. Drowsiness/lethargy occurred most frequently with iloperidone (45%) and least often with lurasidone (8%). Two iloperidone cases had respiratory depression. For asenapine, iloperidone and lurasidone, respectively, management sites were on-site non-health care facility (non-HCF) (32%, 16%, 26%), treated/discharged from emergency department (ED) (46%, 47%, 63%), admitted to noncritical care (9%, 14%, 10%) and admitted to critical care (10%, 22%, 2%). Clinical effect duration was 8?h or less for the majority of non-HCF cases (80%) and for children treated/discharged from the ED (72%). For asenapine, iloperidone and lurasidone, coded outcomes were no effect (50%, 41%, 81%), minor effect (43%, 39%, 17%), moderate (6%, 19%, 2%) and major (0, 2%, 0).

Discussion and conclusions: These findings suggest that in children under 6 years of age, lurasidone exposures were least serious and iloperidone exposures were most serious based on clinical effects, management sites and coded outcomes. Observation of symptomatic children in the ED for 8?h should be sufficient to make triage decisions based on persistence or resolution of clinical effects.     

Toxicity of polysaccharide--iron complex exposures reported to poison control centers

OBJECTIVE: To evaluate the toxicity of polysaccharide-iron complex (PIC) exposures reported to poison centers in the US. DESIGN: A retrospective analysis of potentially toxic exposures to PIC without concomitant substances reported to the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System from 1990 to 1998 was performed. RESULTS: Of 810 potentially toxic exposures to PIC, 55.9% occurred in females, 43.8% in males; in 0.3%, gender was unknown. The majority of exposures (74.4%) involved children under six years of age. The reasons for exposure were: 86.7% unintentional, 11.6% intentional, and 1.6% adverse reaction. The most frequently reported clinical effects attributed to PIC were vomiting (n = 23), diarrhea (10), nausea (11), abdominal pain (10), and lethargy/drowsiness (7). While the majority of exposures were managed outside a healthcare facility, management site varied depending on age (management in non-healthcare facility in 71.8% of exposures in children under six years of age vs. 44.9% in adolescents and adults). The majority of outcomes (95.6%) were no effect, minor effect, unrelated effect, not followed since nontoxic, or not followed since only minimal toxicity possible. Of two cases coded as moderate effect, it could not be determined whether the symptoms were related to PIC in one, and in the second case inspection of the poison center record revealed that the actual outcome was minor effect. There were no major effects or deaths. CONCLUSIONS: There were no serious adverse events following PIC exposure reported to the AAPCC. Although more data are needed, these findings suggest reduced toxicity for PIC relative to other forms of iron.     

NBOMe and 2C substitute phenylethylamine exposures reported to the National Poison Data System

Abstract

Background. Hallucinogenic designer drugs, especially NBOMe and the 2C substitute phenylethylamine series, have been increasing ubiquitous in past years. The purpose of this study is to characterize and compare clinical features of NBOMe and 2C exposures in humans. Method. This is a retrospective cohort study of all single agent exposures to NBOMe and 2C substitute phenylethlamine reported to the National Poison Data System (NPDS) from 1st September 2012 to 30th September 2014. Results. Over the study period, there were a total 341 cases including 148 NBOMe exposures and 193 2C exposures. The majority cases involved men (73.9%); median age was 18 years (Interquartile-range, 16–21). Similar clinical effects were reported in both groups including tachycardia (45.2%), agitation/irritable (44.3%), hallucination/delusion (32.0%), confusion (19.1%) and hypertension (18.5%). There were higher incidences of hallucination/delusion, single episode seizure and benzodiazepine administration in NBOMe exposures (40.5%, 8.8% and 50.0%respectively) than those of 2C exposures (25.4%, 3.1%, and 32.6% respectively). There were 2.3% death; no difference between two groups. Discussion. The higher rate of symptoms in NBOMe is consistent with the higher 5HT2A agonistic effects of NBOMe described in both molecular and animal studies. Conclusion. Common clinical effects of NBOMe and 2C exposures were tachycardia, agitation/irritable, hallucination/delusion, confusion, and hypertension. There were higher incidences of hallucination/delusion, single episode seizure and benzodiazepine administration in NBOMe.     

Evaluation of cosmetic product exposures reported to the Milan Poison Control Centre,Italy from 2005 to 2010

Introduction. To the average consumer, “cosmetics” are not considered to cause damage to human health under normal conditions of use. Thus, cosmetic “safety” does not require any particular attention to the possibility that cosmetics may result in a toxic exposure, especially for children. Poison Control Centres (PCCs) provide specialized and rapid information for consumers and health professionals to ensure management of events related to the exposures to different agents, including Cosmetics. Poison Control Centres also represent a unique source of information to investigate the frequency and type of exposures to cosmetic and the related risks. Objective. An analysis of cases concerning human exposures to cosmetics collected from 2005 to 2010 by the PCC at the Ospedale Niguarda Ca’ Granda (Milan, Italy) was performed. Results. During this period, 11 322 human exposure cases related to cosmetics were collected accounting for 4.5% of the total human clinical cases. Almost, all the requests for assistance came from consumers (53%) and hospitals (40%). The most frequently reported site of exposure was the consumer's own residence (94%). The exposures mainly involved children younger than 4 years (77%). No difference in gender distribution was observed (female 49%, male 51%). Almost, all of the exposures were unintentional (94%). Intentional exposures, mainly related to suicide attempts and accounted for 6% of cases involving persons aged more than 12 years. Personal hygiene products (30%), perfumes and hair care products (excluding hair dyes) (both 13%) were the most frequently involved categories. Symptoms were present only in 26% of the exposures and were mostly gastrointestinal (46%). Most of the cases were managed at home (43%) whereas hospital intervention was required in 38%. Conclusion. Since the exposure frequency seems more likely to reflect product availability and accessibility to ingestors, our results call for closer attention to this type of hazard, especially for children younger than 4 years of age.     

Phenibut exposures and clinical effects reported to a regional poison center

BackgroundPhenibut is a synthetically produced central nervous system (CNS) depressant that is structurally similar to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Phenibut has been identified as a drug of abuse with numerous clinical effects in overdose and a withdrawal syndrome with chronic use. The purpose of this study is to report the incidence of exposure calls regarding phenibut to a poison center, describe the reasons for its use and clinical effects.MethodsStudy subjects were identified using Toxicall®, the electronic medical record utilized by the Minnesota Poison Control System. All phenibut exposure calls from January 2000 through December 2018 were included. Analysis was performed on incidence of exposure calls, reported reasons for use, signs and symptoms, coingestants, and outcome.ResultsThere were 56 exposure calls over 19 years with 48 (85.7%) calls within the past five years. Over 50% of patients had CNS effects and 10.7% had withdrawal concerns. Twenty-seven patients (48%) had abuse as the reason for use and 13 (23%) used phenibut to treat anxiety. There were documented coingestants in 35.7% of patients. No patients died due to reported phenibut use, though 11 patients (19.6%) were intubated.ConclusionExposure calls to a regional poison center regarding phenibut have increased over the past five years. CNS depression was common, and associated with significant clinical outcomes including respiratory failure requiring intubation. As phenibut is easily attainable and exposures appear to be increasing, physicians should be aware of phenibut-associated CNS and respiratory depression and be prepared to manage airways appropriately.     

An 11-year review of bupropion insufflation exposures in adults reported to the California Poison Control System

Background. Seizures of both immediate and delayed onset after ingestion of bupropion SR and bupropion XL formulations are well documented, but are less well characterized after insufflation. Bupropion is crushed and insufflated to experience a high similar to that from amphetamines and cocaine. We sought to characterize the abuse of bupropion via insufflation in cases reported to the California Poison Control System (CPCS) and the incidence of seizures. Methods: An 11-year (2002–2012) retrospective observational case series of insufflated bupropion exposures evaluated in a health care facility (HCF) were reviewed after searching our database for all bupropion insufflation exposures. Patients with coingestants, multiple exposure routes, or age less than 18 were excluded. Data included age, gender, estimated bupropion dose, occurrence of pre-HCF seizures, symptoms and vital signs reported to the CPCS, treatments, and adverse events that occurred until time of discharge. Results: 74 cases were identified (1 excluded due to age, 5 excluded due to additional oral ingestion of bupropion, and 1 excluded due to being unable to follow). A total of 67 cases met inclusion criteria. The median age was 36 (range, 18–65) years. The total dose of bupropion insufflated was reported in 52 pts; median dose of 1500 (range, 100–9000) mg. Eighteen cases (27%) involved staggered or chronic exposures. Of the 67 patients, 20 (30%) experienced a seizure prior to arrival at the HCF. Of these, 19 patients (95%) presented with tachycardia. None of these patients had a second seizure in the emergency department. There were no major medical outcomes and no deaths. Of the 67 patients, 9 patients received benzodiazepines and 6 patients received single-dose activated charcoal. Conclusion: The abuse of bupropion by crushing and insufflating through the nose is uncommon (67/2270 or 3.0%) compared with that by oral bupropion exposures reported to CPCS. Seizures are common but are self-limited. Delayed seizures (more than 8 h after exposure) appear to be rare. Tachycardia is present in almost all patients who have seizures.     

Indicators for serious kidney complications associated with toxic exposures: an analysis of the National Poison Data System

Abstract

Context. Over two million poisoning exposures are reported to U.S. poison control centers annually. A broad population-based survey of toxic exposures and the correlated patterns of reported kidney injury (acute or chronic) have not been systematically characterized. Objective. Our objective was to study the demographic and exposure patterns associated with indicators for serious kidney complications (ISKC), as defined by the variables in the NPDS. Materials and methods. This was a retrospective, case-control study using the data elements available in the NPDS. We assessed data related to patient characteristics, substance exposure, and management. Cases and controls were derived from adult and pediatric exposures documented in NPDS (2001–2007) as having “renal effects.” For substance-specific analyses, cases were restricted to those involving single substances or single entity pharmaceutical preparations. ISKC cases presented with one or more of the following NPDS codes: increased creatinine, and/or oliguria/anuria, and/or renal failure. Controls were subjects with “renal effects” but did not have increased creatinine, nor anuria/oliguria, nor renal failure. Univariate and multivariate logistic regression analyses identified factors associated with ISKC and determined the relationship between these factors. Results. From the approximate 16.8 million exposures reported to the NPDS within the study timeframe, there were 16,444 single substance exposures with renal effects of which 9,074 cases experienced ISKC (55.2%) compared to 7,370 controls without ISKC. Cases with ISKC tended to be males, adults, and reported to involve intentional exposures. Cases with ISKC had higher rates of reported hemodialysis/hemofiltration (27.7%; N = 2,517) and death (10.9%; N = 990) compared to controls, respectively, (2.1%; N = 155) and (0.8%; N = 60), p < 0.001. Substances considered a priori to be nephrotoxic were associated with a higher risk of ISKC. Discussion and conclusion. The NPDS provided insight into the subjects and types of exposures that associate with ISKC. Subjects with ISKC experienced higher rates of morbidity and mortality compared to subjects without ISKC. We identified subject characteristics and classes of compounds associated with ISKC. We hope that the hypotheses generated from this study of the NPDS will raise awareness of the possible risk factors and complications associated with ISKC.     

The association between U.S. Poison Center assistance and length of stay and hospital charges

Context. Poison centers (PCs) play an important role in poison prevention and treatment. Studies show that PCs reduce system-wide cost by reducing the number of unnecessary visits to emergency departments and by providing improved patient management. However, there remains a debate regarding the impact of PCs on patient outcomes at the hospital level. Objective. To evaluate the impact of PC involvement on length of hospitalization and total hospital charges. Materials and methods. We conducted a retrospective analysis of inpatient cases treated in Illinois hospitals in 2010. We linked the Illinois Poison Center database with an Illinois hospital billing dataset and controlled for important patient-level and facility-level covariates. Results. In the multivariable model, length of hospitalization among PC-assisted patients was 0.58 days shorter than that of patients without PC assistance (p < 0.001). Hospital charges for PC-assisted patients in the lower quintiles were significantly higher than patients without PC assistance (+$953; p < 0.001), but were substantially lower in the most costly quintile of patients (?$4852; p < 0.001). Balancing the higher charges for treating patients with PC assistance in the lower quintiles with the savings in the highest quintile, among inpatients there is a potential cumulative decrease of $2,078 in hospital charges per 10 patients. Discussion. Among the inpatient cases, PC assistance was associated with lower total charges only among the most expensive to treat. However, this outlier group is very important when discussing medical costs. It has been repeatedly shown that the majority of treatment costs are attributable to a small fraction of patients as seen in this study.     

U.S. Military veterans and the opioid overdose crisis: a review of risk factors and prevention efforts

U.S. military veterans have been heavily impacted by the opioid overdose crisis, with drug overdose mortality rates increasing by 53% from 2010–2019. Risk for overdose among veterans is complex and influenced by ongoing interaction among physiological/biological, psychological, and socio-structural factors. A thorough understanding of opioid-related overdose among veterans, one that goes beyond simple pharmacological determinism, must examine the interplay of pain, pain treatment, and stress, as well as psychological and social experiences—before, during, and after military service. Comprehensive efforts to tackle the overdose crisis among veterans require interventions that address each of these dimensions. Promising interventions include widespread naloxone distribution and increased provision of low-threshold wrap-around services, including medications for opioid use disorder (MOUD) and holistic/complementary approaches. Interventions that are delivered by peers – individuals who share key experiential or sociodemographic characteristics with the population being served – may be ideally suited to address many of the barriers to opioid-related risk mitigation common among veterans. Community care models could be beneficial for the large proportion of veterans who are not connected to the Veterans Health Administration and for veterans who, for various reasons including mental health problems and the avoidance of stigma, are socially isolated or reluctant to use traditional substance use services. Interventions need to be tailored in such a way that they reach those more socially isolated veterans who may not have access to naloxone or the social support to help them in overdose situations. It is important to incorporate the perspectives and voices of veterans with lived experience of substance use into the design and implementation of new overdose prevention resources and strategies to meet the needs of this population.

Key messages

1. U.S. military veterans have been heavily impacted by the opioid overdose crisis, with drug overdose mortality rates increasing by 53% from 2010–2019.
2. The risks for overdose that veterans face need to be understood as resulting from an ongoing interaction among biological/physiological, psychological, and social/structural factors.
3. Addressing drug overdose in the veteran population requires accessible and non-judgemental, low threshold, wraparound, and holistic solutions that recognise the complex aetiology of overdose risk for veterans.

     

Importance of clinical microbiologists for U.S. healthcare infrastructure

Clinical microbiologists are highly skilled scientists within national hospitals and reference laboratories who diagnose patients with infections by emerging pathogens. Most advanced training for clinical microbiologists occurs at universities, where an individual can receive certification as a "Medical Laboratory Scientist" (MLS). Unfortunately, many MLS programs have closed in the United States and this has caused a shortage of clinical microbiologists at U.S. hospitals and reference laboratories. This paper explores the present crisis in MLS training and its ramifications for the emergence of antibiotic-resistant bacteria, the economics of hospitals, and the overall health of the nation, and provides resolutions for better public health policy with respect to MLS education.     

Ceftazidime-Avibactam Activity against Multidrug-Resistant Pseudomonas aeruginosa Isolated in U.S. Medical Centers in 2012 and 2013

Pseudomonas aeruginosa isolates (n = 3,902) from 75 U.S. medical centers were tested against ceftazidime-avibactam and comparator agents by the reference broth microdilution method. Overall, 96.9% of the strains were susceptible (MIC, ≤8 μg/ml) to ceftazidime-avibactam, while the rates of susceptibility for ceftazidime, meropenem, and piperacillin-tazobactam were 83.8, 81.9, and 78.5%, respectively. Multidrug-resistant and extensively drug-resistant phenotypes were observed in 14.9 and 8.7% of the strains, respectively, and 81.0 and 73.7% of the strains were susceptible to ceftazidime-avibactam, respectively.     

Antimicrobial Activity of Ceftazidime-Avibactam against Gram-Negative Organisms Collected from U.S. Medical Centers in 2012

The activities of the novel β-lactam–β-lactamase inhibitor combination ceftazidime-avibactam and comparator agents were evaluated against a contemporary collection of clinically significant Gram-negative bacilli. Avibactam is a novel non-β-lactam β-lactamase inhibitor that inhibits Ambler class A, C, and some D enzymes. A total of 10,928 Gram-negative bacilli—8,640 Enterobacteriaceae, 1,967 Pseudomonas aeruginosa, and 321 Acinetobacter sp. isolates—were collected from 73 U.S. hospitals and tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories, North Liberty, IA, USA). Ceftazidime was combined with avibactam at a fixed concentration of 4 μg/ml. Overall, 99.8% of Enterobacteriaceae strains were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. Ceftazidime-avibactam was active against extended-spectrum β-lactamase (ESBL)-phenotype Escherichia coli and Klebsiella pneumoniae, meropenem-nonsusceptible (MIC ≥ 2 μg/ml) K. pneumoniae, and ceftazidime-nonsusceptible Enterobacter cloacae. Among ESBL-phenotype K. pneumoniae strains, 61.1% were meropenem susceptible and 99.3% were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. Among P. aeruginosa strains, 96.9% were inhibited at a ceftazidime-avibactam MIC of ≤8 μg/ml, and susceptibility rates for meropenem, ceftazidime, and piperacillin-tazobactam were 82.0, 83.2, and 78.3%, respectively. Ceftazidime-avibactam was the most active compound tested against meropenem-nonsusceptible P. aeruginosa (MIC₅₀/MIC₉₀, 4/16 μg/ml; 87.3% inhibited at ≤8 μg/ml). Acinetobacter spp. (ceftazidime-avibactam MIC₅₀/MIC₉₀, 16/>32 μg/ml) showed high rates of resistance to most tested agents. In summary, ceftazidime-avibactam demonstrated potent activity against a large collection of contemporary Gram-negative bacilli isolated from patients in U.S. hospitals in 2012, including organisms that are resistant to most currently available agents, such as K. pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and meropenem-nonsusceptible P. aeruginosa.     

Comparison of Toxicity of Acute Overdoses with Citalopram and Escitalopram

Background: Seizures and QTc prolongation are associated with citalopram poisoning; however, overdose experience with escitalopram is more limited. Objectives: The goals of this study were to compare citalopram's vs. escitalopram's clinical effects in overdose, including the incidence of seizures. Methods: A retrospective review was conducted for single-substance acute overdoses with citalopram and escitalopram, managed in hospitals, that were reported to six U.S. poison centers from 2002–2005. Results: There were 374 citalopram and 421 escitalopram overdose cases. Gender and ages were similar between the two, with 68–70% females and a median age of 20 years for citalopram and 18 years for escitalopram. Median dose by history was 310 mg for citalopram and 130 mg for escitalopram. More serious outcomes were associated with citalopram overdoses (p < 0.001). Most frequently reported clinical effects with citalopram and escitalopram were tachycardia, drowsiness, hypertension, and vomiting. Seizures (30 vs. 1, respectively, p < 0.001) and tremor (32 vs. 13, respectively, p = 0.001) were more common with citalopram. QTc prolongation occurred in 14 citalopram cases and 7 escitalopram cases (p = 0.109). There was an association between increasing dose and severity of outcome for citalopram (p < 0.001) and escitalopram (p = 0.011). In children < 6 years old, 12 of 66 citalopram and 5 of 57 escitalopram cases experienced toxicity, such as drowsiness, nausea/vomiting, and tachycardia. There were no seizures in this age group. Conclusions: Escitalopram seems to be less toxic than citalopram after an acute overdose; seizures and tremors were more common with citalopram. Initial management of overdoses should include seizure precautions for citalopram and cardiac monitoring for both drugs.