Sarah Vecchio

Metformin accumulation: Lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy

Abstract Objective. The relationship between metformin accumulation and lactate increase is still debated. This observational case series aims to evaluate the correlation of metformin plasma levels with the pH, lactate and creatinine levels, and with the mortality rate in selected patients with metformin accumulation confirmed through metformin plasma concentration detection at hospital admission. Material and methods. All cases of lactic acidosis (pH, ≤ 7.35; arterial lactate, ≥ 5 mmol/L) related to metformin accumulation (plasma level ≥ 4 mcg/mL) from 2007 to 2011 were retrospectively reviewed. Erroneous ingestion and voluntary overdoses were excluded. Epidemiological, medical history, clinical and laboratory data were evaluated in all cases. Results. Sixty-six patients were included. Thirty-one patients (47%) had contraindication to therapy with metformin. All patients showed severe lactic acidosis (pH, 6.91 ± 0.18; lactate, 14.36 ± 4.90 mmol/L) and acute renal failure (creatinine, 7.24 ± 3.29 mg/dL). The mean metformin plasma concentration was 40.68 ± 27.70 mcg/mL. Metformin plasma concentrations showed a correlation, statistically significant even if not strong, with creatinine (p = 0.002, R = 0.37), pH (p < 0.0001, R = − 0.43) and plasma lactate levels (p = 0.001, R = 0.41). Sixty-two (94%) underwent dialysis. Early mortality (before discharge from ICU) was 26% (17 cases). Lactate and metformin concentrations had mean levels not statistically different in surviving and deceased patients. Conclusions. Patients on chronic therapy with metformin may develop a mitochondrial-related toxicity that should be considered when patients present with lactic acidosis, renal failure, and frequently, a medical history of gastrointestinal manifestations during the days preceding the hospital admission. The correlation between metformin plasma concentrations and creatinine, pH, and lactate levels seems to be related to the mechanism of action (inhibition of complex I of the mitochondrial respiratory chain) and to the kinetic properties (high distribution volume and low protein binding) of the drug. The relevant early mortality seems not correlated with the levels of metformin or lactates: this could be due to the possible role of concurrent illness even if, such as for the relationships with lactate and creatinine, a more proper toxicological evaluation could be obtained by assessing metformin erythrocyte concentrations instead of the plasmatic ones.

Adverse Effects of Plant Food Supplements and Plants Consumed as Food: results from the Poisons Centres-Based PlantLIBRA Study

Plant food supplements (PFS) are products of increasing popularity and wide‐spread distribution. Nevertheless, information about their risks is limited. To fill this gap, a poisons centres‐based study was performed as part of the EU project PlantLIBRA. Multicentre retrospective review of data from selected European and Brazilian poisons centres, involving human cases of adverse effects due to plants consumed as food or as ingredients of food supplements recorded between 2006 and 2010. Ten poisons centres provided a total of 75 cases. In 57 cases (76%) a PFS was involved; in 18 (24%) a plant was ingested as food. The 10 most frequently reported plants were Valeriana officinalis, Camellia sinensis, Paullinia cupana, Melissa officinalis, Passiflora incarnata, Mentha piperita, Glycyrrhiza glabra, Ilex paraguariensis, Panax ginseng, and Citrus aurantium. The most frequently observed clinical effects were neurotoxicity and gastro‐intestinal symptoms. Most cases showed a benign clinical course; however, five cases were severe. PFS‐related adverse effects seem to be relatively infrequent issues for poisons centres. Most cases showed mild symptoms. Nevertheless, the occurrence of some severe adverse effects and the increasing popularity of PFS require continuous active surveillance, and further research is warranted. Copyright

Neurotoxicity of European viperids in Italy: Pavia Poison Control Centre case series 2001-2011

Abstract Context. Some clinical aspects about neurotoxicity after snakebites by European viper species remain to be elucidated. Objective. This observational case series aims to analyze neurological manifestations due to viper envenomation in Italy in order to describe the characteristic of neurotoxicity and to evaluate the clinical response to the antidotic treatment, the outcome, and the influence of individual variability in determining the appearance of neurotoxic effects. Materials and methods. All cases of snakebite referred to Pavia Poison Centre (PPC) presenting peripheral neurotoxic effects from 2001 to 2011 were included. Cases were assessed for time from bite to PPC evaluation, Grade Severity Score (GSS), onset/duration of clinical manifestations, severity/time course of local, non-neurological and neurological effects, and antidotic treatment. Results. Twenty-four were included (age, 3–75 years) and represented on average of 2.2 cases/year (about 5% of total envenomed patients). The mean interval time of PPC evaluation from snakebite was 10.80 ± 19.93 hours. GSS at ED-admission was 0 (1 case), 1 (10 cases), and 2 (13 cases). All patients showed local signs: 41.6%, minor; 58.4%, extensive swelling and necrosis. The main systemic non-neurological effects were as follows: vomiting (86.7%), diarrhea (66.7%), abdominal discomfort (53.3%), and hypotension (20%). Neurotoxic effects were accommodation troubles and diplopia (100%), ptosis (91.7%), ophtalmoplegia (58.3%), dysphagia (20.8%), drowsiness (16.6%), cranial muscle weakness (12.5%), and dyspnea (4.2%). Neurotoxicity was the unique systemic manifestation in 9 cases; in 4 cases, they were associated with only mild local swelling. In 10 patients the onset of neurotoxic effects followed the resolution of systemic non-neurological effects. Antidote was intravenously administered in 19 (79.2%) patients. The mean duration of manifestations in untreated versus treated groups was 53.5 ± 62.91 versus 41.75 ± 21.18 hours (p = 0.68, local effects) and 9.77 ± 3.29 versus 8.25 ± 12.23 hours (p = 0.1, systemic non-neurological effects) and 43.4 ± 14.69 versus 26.58 ± 20.62 hours (p = 0.03, neurotoxic effects). Conclusions. Neurotoxicity may appear late (11 hours after the bite in 58.3% of cases), in contrast with the data reported in medical literature. Neurotoxic effects have been reversible in all cases and may be the unique systemic manifestation of envenomation. Neurotoxic effects are shorter in treated group. The antidotic treatment of patients considered as GSS 2 only for neurotoxic effects (with mild local effects) may not be necessary. Variable factors such as different amount of venom injected, concentration of PLA2 component, and individual susceptibility may explain the less percentage of patients presenting neurotoxic effects.

Recurrent tonic - clonic seizures and coma due to ingestion of Type I pyrethroids in a 19-month-old patient

Abstract Context. Pyrethroids are synthetic pyrethrin analogues that induce sodium-channel depolarization and hyperexcitation. Severe pyrethroid poisoning is manifested by a “Tremor Syndrome” (Type I cyano-agents) or a “Choreoathetosis/Salivation Syndrome” (Type II non cyano-agents). Very few reports of neurotoxic effects caused by Type I pyrethroids ingestion are available, and no human data concerning Type I pyrethroid blood levels in pediatric poisoning are reported in the medical literature. Case details. A 19-month-old female patient presented with irritability and inconsolable crying that rapidly worsened to tonic–clonic seizures and coma (GCS 6). On admission vital signs including BP 110/70 mmHg, HR 110 beats/min, and SpO2 98% on room air were normal. Orotracheal intubation, oxygen administration, and midazolam infusion (4 μg/kg/min) were performed. Intravenous thiopental sodium, up to 18 mg/kg/hour, was administered to control convulsions. An inquiry revealed that 9 h before presentation the patient had ingested an unknown amount of an insecticide containing 7% piperonyl-butoxide and a mixture of the Type I pyrethroids bifenthrin (5%) and esbiothrin (3%). Consequently, gastric lavage was performed, followed by administration of activated charcoal and cathartics. On the subsequent 48 h, the patient returned progressively alert; she was extubated on day 4 and discharged asymptomatically 12 days after hospitalization. After 9, 48, and 72 h of ingestion, the plasma levels were 500, 95, and 40 ng/mL for bifenthrin and 1,640, 640, and 165 ng/mL for piperonyl-butoxide respectively. Discussion. This pediatric case showed severe pyrethroid neurotoxicity associated with measurable plasma levels of bifenthrin and piperonyl-butoxide. In pediatric pyrethroid poisoning, coma and seizures may represent the main life-threatening features. First-aid therapy including airway maintenance and control of muscle fasciculation and seizures is of major importance. Benzodiazepines and high-dose thiopental sodium were effective treatments for convulsion.

Fatal course of foodborne botulism in an eight-month old infant

An 8-month old girl, weighing 9 kg, was brought by her parents at 8.15 am to the Emergency Department (ED) for a progressive worsening of weakness and acute respiratory failure. On admission, the baby presented with poor oral intake, a weak cry and extremely weak muscular body control. Poor gag and suck, unreactive mydriasis, hypotonia, lethargy and absence of peristalsis were noted. Laboratory data showed severe respiratory acidosis. Chest X-ray, electroencephalography, encephalic CT scan and MRI were all normal, as were cerebrospinal fluid analysis and viral tests. Orotracheal intubation and continuous mechanical ventilation were applied. The patient received fluids, corticosteroids, aerosol therapy, large-spectrum antibiotics and enteral-nutrition. Further investigation revealed ingestion of an improperly prepared home-canned homogenized turkey meal. Type A botulinum neurotoxin was identified. Trivalent botulinum antitoxin, prostigmine and oral activated charcoal were administered. Generalized flaccid paralysis, areflexic bilateral mydriasis, gastric stasis and deep coma persisted for the duration of the hospital stay, and the patient died of severe respiratory failure and cardiac arrest 12 days after ED admission. Botulism poisoning should be suspected in any infant presenting with feeding difficulties, constipation, descendent paralysis or acute respiratory failure. Supportive treatment and antidotal therapy should be performed as soon as a clinical diagnosis is made. We describe a case of foodborne botulism in an 8-month old infant caused by ingestion of an improperly prepared home-canned homogenized turkey meal, representing the youngest fatal case reported in medical literature.

N-Acetyl-Cysteine as Effective and Safe Chelating Agent in Metal-on-Metal Hip-Implanted Patients: Two Cases

Systemic toxicity associated with cobalt (Co) and chromium (Cr) containing metal hip alloy may result in neuropathy, cardiomyopathy, and hypothyroidism. However clinical management concerning chelating therapy is still debated in literature. Here are described two metal-on-metal hip-implanted patients in which N-acetyl-cysteine decreased elevated blood metal levels. A 67-year-old male who underwent Co/Cr hip implant in September 2009 referred to our Poison Control Centre for persisting elevated Co/Cr blood levels (from March 2012 to November 2014). After receiving oral high-dose N-acetyl-cysteine, Co/Cr blood concentrations dropped by 86% and 87% of the prechelation levels, respectively, and persisted at these latter concentrations during the following 6 months of follow-up. An 81-year-old female who underwent Co/Cr hip implant in January 2007 referred to our Centre for detection of high Co and Cr blood levels in June 2012. No hip revision was indicated. After a therapy with oral high-dose N-acetyl-cysteine Co/Cr blood concentrations decreased of 45% and 24% of the prechelation levels. Chelating agents reported in hip-implanted patients (EDTA, DMPS, and BAL) are described in few cases. N-acetyl-cysteine may provide chelating sites for metals and in our cases reduced Co and Cr blood levels and resulted well tolerable.

Retrospective poisons centres-based study on adverse effects due to plant food supplements

Objective: On-site drug tests (ODTs) are frequently used in hospitals to screen the urine of patients admitted for suspected poisoning. The purpose of this study is to evaluate the accuracy of such ...1. Methanol outbreak in the Czech Republic in 2012: Epidemiology and clinical features Daniela Pelclova1, Sergej Zakharov1, Tomas Navratil1 Knut Erik Hovda2 1Toxicological Information Centre, 1st Medical Faculty, Charles University in Prague, Czech Republic; 2The Norwegian Center for NBC Medicine, Department of Acute Medicine, Oslo University Hospital, Norway Objective: Mass methanol poisonings are a challenge for treating physicians due to the unpredictable onset and scenario, diagnostic difficulties, severe toxicity, expensive treatment, high mortality and frequently serious sequelae.1–4 We report the features of a large methanol outbreak that started in the Czech republic in September 2012 due to the illegal production and sale of adulterated spirits. Methods: Discharge reports and questionnaires of hospitalized patients with confirmed methanol poisoning, received by the Toxicological Information Centre were analyzed. Statistical evaluation used: normality of distribution, arithmetic mean, standard deviation, skew, median, mode, Student’s t-test, F-test, confidence intervals, correlation coefficient, and Chi-Square-test. Results: A total of 73 discharge reports were analyzed. A further 20 patients died at home or before hospital and 5 reports of recently deceased subjects could not yet be analyzed. Among the 73 hospitalized patients, 56 (77%) were males, mean age 51 (range 25–79) years, and 17 (23%) females, mean age 54 (range 23–69) years. Only 9 patients (12%) were admitted within 12 hours of ingestion, 50% after 12–48 hours, and 38% later. All patients who died were admitted 12 or more hours after ingestion. The methanol content of the beverage drunk (25–50%) was known in 42/73 patients (58%), 18/73 (25%) subjects drank other alcoholic beverages (wine, beer, whisky, home-made spirits) in addition. There were 32/73 (44%) daily alcohol users. Admission data: Median serum methanol was 0.939 g/L (range 0–7.307), i.e. 29.4 mmol/L (range 0–229); median ethanol level 0.437 g/L, (range 0–4.460), i.e. 9.6 mmol/L (range 0–98). Median pH was 7.17 (6.57–7.46; N 7.37–7.43), median pCO2 4.07 kPa (0.97-14.9 kPa; N 4.3-6.0), median HCO3  8.8 mmol/L (2–25.5; N 21.8-27.6), median base deficit 17.2 mmol/L (range 0.1–38.1; N 3–3), median lactic acid 3 mmol/L (0–19.4; N 0.6–2.1), median anion gap 28.8 mmol/L (range 11.1–54.8; N 16–20), median osmolality 348 mmol/kg (283–529, N 275–295), and osmolal gap 45.8 mmol/kg (2.4–235, N 10–25). Clinical symptoms: Only 12/73 patients (26%) were asymptomatic on admission, 7 appeared inebriated; at least 3 of them without measurable ethanol in blood. Among the 61 symptomatic patients, the most frequent symptoms were gastrointestinal (63%), visual disturbances (59%), dyspnoea (46%), coma (29%) and chest pain (17%). Other symptoms included fatigue, headache, dizziness, hangover, somnolence, anxiety, tremor, seizures, alcoholic delirium, respiratory and cardiac arrest. Treatment included alkalinization in 64%, ethanol in 79%, fomepizole in 5%, or a combination of antidotes in 12% patients. because there was limited availability of fomepizole, it was only recommended for the most severely poisoned subjects with methanol level above 0.500 g/L (15.65 mmol/L) or formic acid above 0.400 g/L (8.7 mmol/L) or pH lower than 7.0. Folates were administered in 72% of subjects (folic acid in 33 patients, folinic acid in 20 patients); whereas haemodialysis was performed in 58/73 (79.5%) subjects and started on average 4 hours after admission to the hospital (range 0.5–44). Continuous veno-venous haemodialysis (CVVHD) was performed in 50% of subjects; lasting a median of 36 hours (range 3.5–95). Conventional intermittent haemodialysis (IHD) was performed for a median duration of 8 hours (range 4–18.5). Outcomes: There were 13/73 (18%) fatalities, 44/73 (60%) survivors without sequelae, and 16/73 (22%) survivors with sequelae: visual impairment alone in 7/73 (10%), central nervous system (CNS) impairment in 5/73 (6.5%) and both visual and CNS damage in 4/73 (5.5%). The mortality was 75% among the patients admitted with respiratory arrest and 52% among those comatose on admission. The patients who died were more (p  0.05) acidotic (median pH 6.75, median base deficit 30 mmol/L) than the survivors with sequelae (median pH 7.02, median base deficit 19 mmol/L) and than those without (median pH 7.26, median base deficit 8 mmol/L), (p  0.05). No significant differences were found between the 3 groups regarding serum methanol, osmolal gap, and HCO3 . The groups differed only in pCO2, pH and base deficit (all p  0.05). Among the patients who recovered without sequelae, there was a trend towards lower pCO2 when pH was decreasing, whilst the trend was the opposite amongst the victims (pH decreased and pCO2 increased). The difference between these groups was highly significant (p  0.001). Lactic acid was significantly higher in victims than survivors (p  0.01). Among the 58 patients treated with ethanol, 9 (16%) died, 9 (16%) survived with sequelae, and 40 (68%) recovered fully. Among the 13 patients treated with fomepizole or the combination of antidotes, 3 (23%) died, 6 (46%) survived with sequelae, and 4 (31%) recovered, i.e. the outcome was worse in the second group (p  0.023). There was no difference in survival between the patients treated with continuous veno-venous haemodialysis (CVVHD) and IHD (p  0.17).Background: Of the 90,000 exposures involving children younger than 6 years of age reported to German poison centers (PCs) every year a !fth are caused by plants. A list of especially poisonous plants, which should not be planted in children’s playgrounds, was published in the “Bundesanzeiger” (Federal Gazette) in 2000. The BfR-Committee “Assessment of Intoxications” founded a work- ing group to re-assess the toxicity of plants to protect especially children from severe plant poisoning. Methods: The members of the working group de!ned criteria for risk assessment of plants in the close proximity of children’s playgrounds. Human exposure data, provided by the German PCs in Berlin, Freiburg and Erfurt and by the Swiss PC Zurich were reviewed as well as scienti!c publications about human exposures and about toxicity of ingredients of plants. Following the assess- ment of the toxicity of chemicals in analogy to the German Regula- tions on Dangerous Substances, poisonous plants were re-classifed into three categories, namely plants which could lead to minor poisoning, moderate poisoning and severe or deadly poisoning. Results: Out of 43,000 con!rmed accidental plant exposures from PCs in Freiburg and Berlin moderate or severe poisoning was expe- rienced in 1.3% restricted to 39 plants. Altogether, 280 plants were re-evaluated. Risk assessment changed for some of the especially poisonous plants of the 2000 list. For example the formerly moder- ate poisonous plants Lantana camara, Ilex spec., and Euonymus spec. were re-assessed as minor poisonous, and the formerly minor toxic Chelidonium majus was re-assessed as moderately toxic for the eyes. Conclusion: Human data about the risk of health damage after accidental ingestion of small amounts or by accidental dermal or ocular contact are mainly restricted to published case reports. The toxicity of ingredients and of preparations of plants for medical or psychoactive purposes may be completely different. The exposure data of PCs are very useful for risk assessment of plants present in the close proximity of children’s playgrounds, kindergartens, etc. The re-assessment and the !nal table of especially poisonous plants will be published again in the “Bundesanzeiger”.Background On the 21st June 2010, the management advice on TOXBASE® (the UK poisons database) for toothpaste ingestion changed, from advising medical assessment in patients developing anything other than minor gastrointestinal symptoms to advising observations in patients ingesting over 5 mg/kg fluoride, and further management in those ingesting over 10 mg/kg fluoride. We investigated the amounts ingested, features present, and advice given in cases of acute toothpaste ingestion reported to the NPIS three years before, and two years after, this change.Background: In 2009, in a joint cooperation, the Federal Institute for Risk Assessment (BfR) carried out an investigation concerning the poisoning situation of children, but with indifferent results for the poisoning risks in migrants. Between 2010 and 2011 some scientific assumptions were published in Germany that migrants could carry a higher risk of childhood poisoning. A feasibility study in Berlin, however, evaluated the options for achieving access to families with a migrant background in order to develop a framework for further, enlarged and systematically established scientific studies. Method: Existing data on migration background were evaluated regarding risks of chemical consumer products being responsible for childhood household poisoning accidents. The main instrument was a semi-standardised questionnaire for parents. Subject matter was focused on poisoning accidents which had occurred; knowledge about chemical products; attitudes towards the use of those products, their household storage and safety aspects and an important item “looking through the keyhole”. This means that if respondents agreed an expert would make a home-visit to evaluate real household product knowledge together with poisoning risks for children. Results: Regarding the cases of childhood poisoning accidents, the study did not support the assumption of a higher rate of relevant accidents in families with a migrant background - on the contrary, accidents occurred mainly in families with minor chemical use. There was no obvious correlation between age of the parents, family status, job, dwelling, knowledge about the products or their possible risks and causes of poisonings. In three-quarters of the cases, the affected children were the eldest. Possible impacts to be evaluated are e.g. the knowledge which might well have its origin in a specific cultural setting - about handling and risks of chemical products and the level of knowledge of the German language. Furthermore, more than half of the respondents agreed to an expert’s visit to their home. Conclusion: In order to develop adequate means of prevention in childhood poisoning, the focus has to be taken to special target groups and the evaluation of specific instruction materials. It is of nationwide importance to get personal access to the migrants. A combination of legal and educationally oriented measures seems promising.Objective: Since 20 January 2009, the EU-CLP Regulation (EC) No. 1272/2008 (Classification, labelling and packaging of substances and mixtures) has been in effect. Article 45 stipulates compulsory reporting of formulations of mixtures by industry for emergency health services. For adaptation of the CLP Regulation on a national level, the German government implemented Art. 45 CLP-Regulation into the § 16e (Chemicals Law - Chemikaliengesetz). For a transition period (9th November 2011 limited to the 1st July 2014) German industry can already start to use “Art. 45-Electronic Product Notification” via an adapted BfR-Electronic Product Notification Portal. Methods: Since 2007, notification of formulations of detergents and cleaning agents has been performed by file transfer in XML-format. This procedure was developed by the BfR and had been well adopted by industry. This format was refined by the BfR to ensure that data on all notifiable products and data reported on a voluntary basis can be transmitted in XML-format. This prototype and the procedures have been practice-tested in cooperation with a major enterprise (Henkel, Dusseldorf). After final testing the BfR-database has been adapted to the new requirements of the CLP-Regulation on e.g. labelling and all important data, including clear identifiers (e.g. product identification element) which can be exchanged in the new format. Results: The § 16e (new) has been successfully adapted to the CLP Regulation (EC) No. 1272/2008: 1) governed by public law with a transition period in awaiting the EU-harmonisation dataset for product notifications and 2) technical in having an adapted BfR-XML Electronic Notification Portal which carries all the requirements for the rapid adaptation to the future EU standard data set. With the new § 16e the notification of dangerous mixtures is considerably extended. Products with all hazard identifiers – commercial/non-commercial – have to be notified. The increase is already visible in 2012. From January to October 38,735 dangerous mixtures (excluding biocides) had been notified. This represents a 25-fold increase compared to 2011. Conclusion: A universal electronic notification procedure for industry will enable BfR to considerably increase the number of product notifications received, processed and communicated to German PCCs.Background A survey of all European Poisons Centres (PCs) was carried out in 2012 by the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) in order to identify staffing, organisation, In 2012 all centres required information staff to have at least a university degree, with the exception of one that employed nongraduate nurses (96.9% compared with 81.7% requiring a university degree in 2000). services provided, research and training. The objective was to describe the working of the centres and perhaps to provide help where needed in the future.

Treatment of foodborne botulism in current clinical toxicology: authors’ reply

Dr. Zamani pointed out the role of the whole bowel irrigation (WBI) with polyethylene glycol as an appropriate adjunctive option of gastrointestinal decontamination in severe botulism poisoning. Secondly, the author underline the early administration of trivalent antitoxin as soon as clinical suspicion of botulism poisoning is made.1 However in the case described there are some considerations that need to be evaluated.2 First of all, regarding the gastrointestinal decontamination in severe botulism poisoned patient, all procedures aimed to remove spores and toxin from the gut should be applied. In details when post-pyloric decontamination with cathartic agents must be performed, sorbitol should be preferable than magnesium salts because the latter may exacerbate neuromuscular blockade.3 WBI may have a theoretical role in decontamination and it could be evaluated in severe poisoning.3 However, these procedures may be difficult and their efficacy may be reduced in the presence of drug- or toxin-induced ileus.4 In some cases prostigmine, which inhibits the enzymatic degradation of acetylcholine, appears to be useful in reversing ileus.5 In our case, the prolonged absence of peristalsis and the gastric stasis made cathartic agents administration difficult; in fact gastrointestinal decontamination with nasogastric tube, activated charcoal oral administration and intravenous prostigmine were performed to reduce the toxin absorption and to promote the gut peristalsis. About the timing of antidote administration, it should keep in mind that the aim of the antitoxin therapy consists in neutralizing the circulating toxin molecules still unbound to the nerve endings: this mechanism of action limits the involvement of new nerve endings, but cannot reverse the paralysis nor neutralize the toxins already bound to the nerve receptors.4 The clinical picture of our baby was severe still at admission (severe respiratory failure with hypoxemia and metabolic acidosis) and rapidly worsening consistent with the ingestion of a large dose of type A toxin, the most potent type of botulinum neurotoxins. In our case, trivalent antitoxin was administered about 10 hours after laboratory confirmation. Little age of the infant, the insidious onset of clinical manifestation, the rapid worsening of respiratory and neurological features and initial lack of specific history for a food source at hospital admission made the diagnostic suspicion difficult and delayed by differential diagnosis procedures (e.g. chest X-ray, electroencephalogram, cranial-computed tomography and magnetic resonance imaging scan, cerebrospinal analysis). Moreover when foodborne botulism was suspected, the antidote was immediately requested and obtained from the Health Ministry Stockpile after the laboratory confirmation was obtained. As Dr. Zamani correctly observed, an immediate antitoxin administration should be evaluated both in symptomatic patients and asymptomatic individuals recently exposed to a presumptive food source.1 In fact, the antitoxin should be administered also before the laboratory results, immediately as soon as clinical suspicion of botulism poisoning is suspected.4 In our case: i) a positive history for food consumption was not promptly reported on hospital admission, ii) the clinical suspicion for botulism poisoning was difficult and unfortunately hypothesized late and iii) antitoxin research was performed only after laboratory confirmation: these aspects made the diagnosis and the treatment of this case of severe foodborne botulism complicated and not as timely and prompt as theoretically desired.