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Aquilino Neadstine
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Background: Antimicrobials are the most commonly prescribed drugs. Many studies have evaluated antibiotic prescriptions in the paediatric outpatient but few studies describing the real antibiotic consumption in Italian children's hospitals have been published. Point-prevalence survey (PPS) has been shown to be a simple, feasible and reliable standardized method for antimicrobials surveillance in children and neonates admitted to the hospital. In this paper, we presented data from a PPS on antimicrobial prescriptions carried out in 7 large Italian paediatric institutions.
Methods: A 1-day PPS on antibiotic use in hospitalized neonates and children was performed in Italy between October and December 2012 as part of the Antibiotic Resistance and Prescribing in European Children project (ARPEC). Seven institutions in seven Italian cities were involved. The survey included all admitted patients less than 18 years of age present in the ward at 8:00 am on the day of the survey, who had at least one on-going antibiotic prescription. For all patients data about age, weight, underlying disease, antimicrobial agent, dose and indication for treatment were collected.
Conclusions: Our study provides insight on the Italian situation in terms of antibiotic prescriptions in hospitalized neonates and children. An over-use of third generation cephalosporins both for prophylaxis and treatment was the most worrisome finding. A misuse and abuse of carbapenems and quinolones was also noted. Antibiotic stewardship programs should immediately identify feasible targets to monitor and modify the prescription patterns in children's hospital, also considering the continuous and alarming emergence of MDR bacteria.
A 1-day PPS on antibiotic use in hospitalized neonates and children was performed in Italy between October and December 2012 as part of the Antibiotic Resistance and Prescribing in European Children project (ARPEC). Seven institutions in seven Italian cities were involved. The survey included all admitted patients less than 18 years of age present in the ward at 8:00 am on the day of the survey, who had at least one on-going antibiotic prescription. For all patients data about age, weight, underlying disease, antimicrobial agent, dose and indication for treatment were collected.
Copyright: 2016 De Luca et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Antimicrobials are the most commonly prescribed drugs in the community and hospital setting, especially among paediatric patients [1]. However, antibiotics are often unnecessarily used both in the community, where too many children receive broad-spectrum antibiotics for viral infections, and in the hospital, where long courses of broad-spectrum antibiotics are frequently prescribed [2]. Recent studies have found that up to 50% of antimicrobial prescriptions are inappropriate [3,4].
Many studies have evaluated antibiotic prescriptions in the paediatric outpatient population highlighting the problem that Italian prescribing habits that differ from those of other European countries. An Italian child is more likely to be exposed to antibiotics than children are in North Europe [10] and, in particular, the prevalence of antibiotic prescriptions in childhood have been reported to be 4 times higher than in the UK and 6 times higher than in the Netherlands [11,12]. Moreover, Italy reported the highest prescription rate (1.3 per infants per year) in a study comparing antibiotic use in the first year of life in five European countries [13]. In fact, data from the Gagliotti et al study in 2006 show that the 55% of Italian infants in the community have already received at least one course of antibiotics at 1 year of age and 84% at 2 years of age [14].
In this paper, we present the results of a point-prevalence survey (PPS) on antibiotic prescriptions carried out in seven large Italian paediatric institutions in 2012. The aims of our study were: i) to describe prevalence rates of antibiotic prescriptions for prophylaxis and treatment of infections for neonatal (
This research has been conducted according to the principles expressed in the Declaration of Helsinki. Ethical approval has been obtained for the coordinating centre. No consent was given, because data were collected by reviewing medical charts and were analyzed anonymously. Every patient record was given a unique non-identifiable survey number, which was automatically generated by a computer program specifically designed for anonymous data entry.
A 1-day PPS on antibiotic use in hospitalized children was performed in Italy between October and December 2012 as part of the Antibiotic Resistance and Prescribing in European Children project (ARPEC). Seven paediatric or mixed adult-paediatric hospitals in seven Italian cities were involved (Genoa, Milan, Padua, Florence, Viareggio, Rome and Naples). The survey included all admitted patients less than 18 years of age present in the ward at 8:00 am on the day of the survey who had at least one on-going antibiotic prescription. The wards of admission were: medical (general neonatal and maternal wards, and general paediatric wards), special medical (cardiology, nephrology, onco-hematology, neuromuscolary, neurology, bronchopneumology, infectious diseases unit), neonatal and paediatric intensive care (NICUs and PICUs), surgical (neonatal surgery, paediatric surgery, orthopedics, neurosurgery). For feasibility reasons, one hospital provided data from randomly selected wards, maintaining the patient distribution among medical, special medical, surgical and intensive care units, in agreement with the coordinating centre. Full details of the ARPEC methodology are described elsewhere [18].
Characteristics of all patients enrolled are summarized in Table 2. Median patient age was 24 months and 12.3% were less than 30 days old. Overall, 24.6% of patients were affected by a medical/surgical underlying condition and the most frequent was an oncologic/hematologic disease. Noteworthy is that the rate of oncologic/hematologic patients admitted to the hospital at the time of the survey was 5% (45/899), but this rate increased to 22.3% (78/349) looking at the group of patients receiving antibiotics. These data reflect the fact that oncologic and hematologic patients were responsible for a large proportion of antibiotic consumption in our survey.
The main indication to prescribe antibiotic prophylaxis was medical risk factors (e.g. prematurity, maternal fever during labor, prolonged rupture of the membranes), accounting for 55.8% of all indications for antibiotic therapy in the neonatal subset. The other neonatal patients were receiving prophylaxis for surgical reasons. Monotherapy was prescribed in 10 of the 27 patients on prophylaxis (37%), and penicillin was the most prescribed antibiotic (7/10). Combination therapies in the other 17/27 patients (63%) were variable: penicillins were combined with aminoglycosides in 7/17 cases, while glycopeptides were used with third generation cephalosporins in 3 cases and with aminoglycosides in 3 cases. The last 4 patients received 3 drug combination therapy, including glycopeptides plus aminoglycosides combined with metronidazole (2/4) or penicillin (2/4).
Among all the indications for antibiotic treatment of infection in neonates, the most common was sepsis (30.2%, 13/43). Monotherapy was used just in two cases (one case treated with ampicillin and the other treated with meropenem). Penicillins plus aminoglycosides was by far the preferred combination therapy (8/11), while in the other patients (3/11) glycopeptides were used widely in combination with other classes of antibiotics.
The 1-day ARPEC PPS provided very useful data on hospital antibiotic prescriptions for paediatric and neonatal patients in Italy. According to data collected in seven large Italian institutions, 38.9% of inpatients received at least one antibiotic prescription during hospitalization. This rate is similar to the mean rate reported from the worldwide ARPEC PPS (36.7%) [18].
In the paediatric group, the rate of antibiotic prescriptions for prophylaxis was 35.5% of all the prescriptions. Approximately, half of these patients were receiving antibiotics for surgical prophylaxis in accordance with previous European reports in which the proportion of children receiving surgical prophylaxis ranged from 13 to 42% [25, 26]. Third generation cephalosporins ranked first in prescription frequency in this scenario, used often in monotherapy but combined with metronidazole in some cases, confirming their alarming overuse for this indication. This problem in fact was already raised by Ciofi et al in 2008 [16], but a recent paper published by Buccellato et al in 2015 shows that a limitation on the prescriptions of these drugs has not yet been reached [17]. However, it is worth noting that this finding was very variable among the seven centers, since some hospitals preferred the first generation cephalosporins for surgical prophylaxis, as suggested by international guidelines [27].
Cotrimoxazole was the most prescribed antibiotic for medical prophylaxis, used alone in most cases. As explanation, most of the treated children were affected by onco-hematological diseases and cotrimoxazole is the best treatment to prevent Pneumocystis jirovecii pneumonia in immunocompromised patients [28].
Regarding the prescription patterns for treatment of infection, the 37.2% of our neonatal cohort was prescribed at least one antibiotic for treating an infection, the main reason was sepsis and the most common antibiotic class was penicillins, combined with aminoglycosides in a large number of patients, in line with international literature [29, 30]. It is hard to compare prescription habits in our centres with other NICUs because of a wide variability of the rate of neonates prescribed antibiotics across hospitals, as shown by a recent multicenter study involving 127 NICUs in the US [31]. The 40-fold variations in prescription frequencies noted in this study did not appear to be related to higher infection burden, necrotizing enterocolitis incidence, surgical volume or mortality rate [31]. They have instead been attributed to frequent inappropriate courses of antibiotics in inpatient neonates, more commonly owing to an unnecessary antibiotic continuation than starting of a non-required therapy [32].
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