Substandard and falsified antimicrobials in selected east African countries: A systematic review.

BACKGROUND: Globally, millions of people have been affected by fraudulent pharmaceutical products, particularly those in developing countries. Although the problem of falsified and substandard drugs is acknowledged, the extent of the issue is ever-changing, has a dynamic nature, and should be quantified and captured in a recent snapshot. OBJECTIVE: This systematic review seeks to examine the data that can quantify and provide a current snapshot of the prevalence of SF antimicrobials in selected east Africa countries. METHODS: Scientific studies on antimicrobial quality were searched in PubMed, Embase, Scopus, and Google Scholar from 2017 to February 2023. The search strategy focused on scientific articles published in peer-reviewed scientific journals written in English and the studies exclusively done in any of the selected countries of east Africa. The articles were carefully reviewed by two individuals for inclusion independently, first by title followed by abstract and the full-text retrieval. To minimize bias associated with the methodology used for data collection, the quality of the studies was assessed for quality according to the Medicine Quality Assessment Reporting Guidelines (MEDQUARG). The reporting of this systematic review was done following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). RESULTS: Fifteen studies that estimated the prevalence of poor-quality antimicrobial medicines in selected four east African countries were included. The overall percentage of samples of antimicrobials that failed at least one quality test was 22.6% (151/669) with each class's prevalence of 17% in antibiotics (73/432), 24% in antimalarial (41/171), and 56% in anthelmintics (37/66). Quality control parameters of API content were the most commonly examined in the included studies, accounting for 14/15 (93%) studies. Fifty (33.1%) of the failing samples failed assay API- content determination, while 26.5% (n = 40) failed the visual inspection and packaging analysis; 19.2% (29) failed dissolution; 14% (n = 21) flawed hardness or friability; 4%(n = 6) failed uniformity, as well as 3.2% (n = 5) failed disintegration test of the quality control parameter. CONCLUSION: It was found that this review was general in these selected east African countries and was a catalyst for combating the menace of poor-quality medications that affect millions of lives.

Ceftolozane/tazobactam versus meropenem in patients with ventilated hospital-acquired bacterial pneumonia: subset analysis of the ASPECT-NP randomized, controlled phase 3 trial.

BACKGROUND: Ceftolozane/tazobactam is approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) at double the dose approved for other infection sites. Among nosocomial pneumonia subtypes, ventilated HABP (vHABP) is associated with the lowest survival. In the ASPECT-NP randomized, controlled trial, participants with vHABP treated with ceftolozane/tazobactam had lower 28-day all-cause mortality (ACM) than those receiving meropenem. We conducted a series of post hoc analyses to explore the clinical significance of this finding. METHODS: ASPECT-NP was a multinational, phase 3, noninferiority trial comparing ceftolozane/tazobactam with meropenem for treating vHABP and VABP; study design, efficacy, and safety results have been reported previously. The primary endpoint was 28-day ACM. The key secondary endpoint was clinical response at test-of-cure. Participants with vHABP were a prospectively defined subgroup, but subgroup analyses were not powered for noninferiority testing. We compared baseline and treatment factors, efficacy, and safety between ceftolozane/tazobactam and meropenem in participants with vHABP. We also conducted a retrospective multivariable logistic regression analysis in this subgroup to determine the impact of treatment arm on mortality when adjusted for significant prognostic factors. RESULTS: Overall, 99 participants in the ceftolozane/tazobactam and 108 in the meropenem arm had vHABP. 28-day ACM was 24.2% and 37.0%, respectively, in the intention-to-treat population (95% confidence interval [CI] for difference: 0.2, 24.8) and 18.2% and 36.6%, respectively, in the microbiologic intention-to-treat population (95% CI 2.5, 32.5). Clinical cure rates in the intention-to-treat population were 50.5% and 44.4%, respectively (95% CI - 7.4, 19.3). Baseline clinical, baseline microbiologic, and treatment factors were comparable between treatment arms. Multivariable regression identified concomitant vasopressor use and baseline bacteremia as significantly impacting ACM in ASPECT-NP; adjusting for these two factors, the odds of dying by day 28 were 2.3-fold greater when participants received meropenem instead of ceftolozane/tazobactam. CONCLUSIONS: There were no underlying differences between treatment arms expected to have biased the observed survival advantage with ceftolozane/tazobactam in the vHABP subgroup. After adjusting for clinically relevant factors found to impact ACM significantly in this trial, the mortality risk in participants with vHABP was over twice as high when treated with meropenem compared with ceftolozane/tazobactam. TRIAL REGISTRATION: clinicaltrials.gov, NCT02070757. Registered 25 February, 2014, clinicaltrials.gov/ct2/show/NCT02070757.

Treatment of the lung injury of drowning: a systematic review.

BACKGROUND: Drowning is a cause of significant global mortality. The mechanism of injury involves inhalation of water, lung injury and hypoxia. This systematic review addressed the following question: In drowning patients with lung injury, what is the evidence from primary studies regarding treatment strategies and subsequent patient outcomes? METHODS: The search strategy utilised PRISMA guidelines. Databases searched were MEDLINE, EMBASE, CINAHL, Web of Science and SCOPUS. There were no restrictions on publication date or age of participants. Quality of evidence was evaluated using GRADE methodology. RESULTS: Forty-one papers were included. The quality of evidence was very low. Seventeen papers addressed the lung injury of drowning in their research question and 24 had less specific research questions, however included relevant outcome data. There were 21 studies regarding extra-corporeal life support, 14 papers covering the theme of ventilation strategies, 14 addressed antibiotic use, seven papers addressed steroid use and five studies investigating diuretic use. There were no clinical trials. One retrospective comparison of therapeutic strategies was found. There was insufficient evidence to make recommendations as to best practice when supplemental oxygen alone is insufficient. Mechanical ventilation is associated with barotrauma in drowning patients, but the evidence predates the practice of lung protective ventilation. There was insufficient evidence to make recommendations regarding adjuvant therapies. CONCLUSIONS: Treating the lung injury of drowning has a limited evidentiary basis. There is an urgent need for comparative studies of therapeutic strategies in drowning.

A comparison of E. coli susceptibility for amoxicillin/clavulanic acid according to EUCAST and CLSI guidelines.

In our tertiary care center, the reported susceptibility of E. coli blood isolates to amoxicillin/clavulanic acid exceeded 90% in 2005 and showed a progressive decrease to 50% by 2017. In this study, we investigate whether there is a real increase in resistant E. coli strains or if this apparent decline in reported susceptibility might be attributed to the substitution of CLSI by EUCAST guidelines in 2014. We randomly selected 237 E. coli blood isolates (stored at - 80 °C) from 1985 to 2018 and reassessed their MIC values, applying both the CLSI (fixed ratio of clavulanic acid) and EUCAST guidelines (fixed concentration of clavulanic acid). In parallel, the susceptibility of these isolates was retested by disk diffusion, according to the EUCAST guidelines. Whole genome sequencing was successfully performed on 233 of the 237 isolates. In only 130 of the 237 isolates (55.0%), testing according to the EUCAST and CLSI criteria delivered identical MIC values for amoxicillin/clavulanic acid. In 64 of the 237 isolates (27.0%), the MIC values diverged one dilution; in 38 (16.0%), two dilutions; and in five (2.1%), three dilutions. From these 107 discrepant results, testing according to EUCAST methodology revealed more resistant profiles in 93 E. coli strains (94.1%). Also, phenotypical susceptibility testing according to EUCAST guidelines tends to correlate better with the presence of beta-lactamase genes compared to CLSI testing procedure. This study highlights the low agreement between EUCAST and CLSI methodologies when performing MIC testing of amoxicillin/clavulanic acid. More strains are categorized as resistant when EUCAST guidelines are applied. The low agreement between EUCAST and CLSI was confirmed by WGS, since most of EUCAST resistant/CLSI sensitive isolates harbored beta-lactamase genes.

Prevalence of Substandard Amoxicillin Oral Dosage Forms in the National Capital District of Papua New Guinea.

Antibiotics are commonly reported as being substandard or falsified in low- to middle-income countries, having potential to contribute to the development of antimicrobial resistance and drug-resistant infections. Amoxicillin, used to treat a number of infections and listed by the WHO as an essential medicine, presented as a good drug candidate for this study. We aimed to measure the prevalence of substandard and falsified amoxicillin oral products (tablets, capsules, and suspensions) in the National Capital District of Papua New Guinea (PNG). These oral products were surveyed in 2018 and 2019 from retail pharmacies, private and public health facilities, and the Area Medical Store, representing more than 90% of licensed medicine outlets. The product packaging was visually inspected, and the samples were analyzed for amoxicillin content using a validated high-performance liquid chromatography method. Although no falsified products were identified, 15% of the 190 products analyzed contained substandard amounts of amoxicillin. Quality varied with the dosage form (P = 0.002), with capsules exhibiting the lowest incidence of substandard content (4% in 2019) and tablets collected in 2018 experiencing the highest failure rate (50%). Suspension (40%) quality was compromised by failure to achieve homogeneity on reconstitution. A higher incidence of substandard content (P = 0.002) was associated with one major retail group. Routine testing of medicines by resource-poor countries is often unachievable, leading to the circulation of poor quality drugs, which is a global public health concern. Our study highlighted that substandard amoxicillin oral products are indeed prevalent in the NCD of PNG.

Preparation and evaluation of an innovative antibacterial bi-layered composite dressing for skin wound healing.

AIM OF THE STUDY: The aim of the current study was to develop collagen-based bi-layered composite dressings with antibacterial property and evaluate the efficiency for wound healing. MATERIALS AND METHODS: A bi-layered composite wound dressing was fabricated using two marine biomacromolecules (collagen and chitosan or carboxymethyl chitosan). Non-crosslinked and N-Ethyl-N'-(3-dimethylaminopropyl) carbodiimide/N-Hydroxy succinimide (EDC/NHS) cross-linked collagen sponges fabricated by vacuum freeze-drying technology was used as the inner layer. The medical spun-laced nonwoven coated with chitosan and carboxymethyl chitosan was used as the outer layer. The antibacterial activities against E. coli and S. aureus were evaluated by the inhibition zone assay. Deep second-degree scald model was performed to evaluate the efficiency of bi-layered composite dressings for wound healing. RESULTS: In view of comprehensive evaluation of appearance and in vitro antibacterial activity, medical spun-laced nonwoven coated with 3% of chitosan solution was chosen to be used as the optimized preparation conditions to produce the outer layer of composite dressing, which acted as a barrier against microorganisms and provided mechanical support. Furthermore, the results of wound closure and histopathological analysis indicated that EDC/NHS cross-linked collagen-based bi-layered composite dressing was superior to non-crosslinked and commercial products, which stimulated the wound healing process and accomplished deep second-degree scalded skin healing within a time span of 28 days. CONCLUSION: The EDC/NHS cross-linked collagen-based bi-layered composite dressing had immense potential to be applied for an ideal wound dressing for more efficient and faster wound healing. Therefore, the findings provided the essential theoretical basis for great potential of collagen-based composite dressing used in wound healing applications.

Changes in treatment of community-onset Clostridioides difficile infection after release of updated guidelines, Atlanta, Georgia, 2018.

Updated Clostridioides difficile infection (CDI) guidelines published in 2018 recommend vancomycin as first-line treatment. Of 833 community-onset CDI cases in metropolitan Atlanta, Georgia in 2018, over half did not receive first-line treatment, although guideline adherence increased over the year. Second-line treatment was more common in patients treated in ambulatory settings.

Antibiotic Safety and Effectiveness in Premature Infants With Complicated Intraabdominal Infections.

BACKGROUND: In premature infants, complicated intraabdominal infections (cIAIs) are a leading cause of morbidity and mortality. Although universally prescribed, the safety and effectiveness of commonly used antibiotic regimens have not been established in this population. METHODS: Infants ≤33 weeks gestational age and <121 days postnatal age with cIAI were randomized to ≤10 days of ampicillin, gentamicin, and metronidazole (group 1); ampicillin, gentamicin, and clindamycin (group 2); or piperacillin-tazobactam and gentamicin (group 3) at doses stratified by postmenstrual age. Due to slow enrollment, a protocol amendment allowed eligible infants already receiving study regimens to enroll without randomization. The primary outcome was mortality within 30 days of study drug completion. Secondary outcomes included adverse events, outcomes of special interest, and therapeutic success (absence of death, negative cultures, and clinical cure score >4) 30 days after study drug completion. RESULTS: One hundred eighty infants [128 randomized (R), 52 nonrandomized (NR)] were enrolled: 63 in group 1 (45 R, 18 NR), 47 in group 2 (41 R, 6 NR), and 70 in group 3 (42 R, 28 NR). Thirty-day mortality was 8%, 7%, and 9% in groups 1, 2, and 3, respectively. There were no differences in safety outcomes between antibiotic regimens. After adjusting for treatment group and gestational age, mortality rates through end of follow-up were 4.22 [95% confidence interval (CI): 1.39-12.13], 4.53 (95% CI: 1.21-15.50), and 4.07 (95% CI: 1.22-12.70) for groups 1, 2, and 3, respectively. CONCLUSIONS: Each of the antibiotic regimens are safe in premature infants with cIAI. CLINICAL TRIAL REGISTRATION: NCT0199499.

Comparative Quality Evaluation of Selected Brands of Cefuroxime Axetil Tablets Marketed in the Greater Accra Region of Ghana.

The ever-growing commercialization of poor-quality and substandard medicines, especially anti-infectives characterized by inadequate postmarket surveillance by stakeholders remains a major global health challenge, particularly in developing countries, where antibiotic drug resistance and its repercussions on human health remain dominant. This research sought to evaluate the pharmaceutical quality of six randomly selected brands of cefuroxime axetil tablets (250 mg) marketed in the Greater Accra region of Ghana. The selected brands were coded and subjected to both compendial and noncompendial tests. Statistical analysis and model-independent parameter (similarity factor, f2) were employed in analyzing the dissolution profiles of all the brands. All brands including the reference brand conformed to the pharmacopeial specifications for both compendial and noncompendial tests, indicating that they were of good quality. However, there were significant variations (p < 0.05) in the disintegration time amongst the various brands. All the brands had ƒ2 values > 50 indicating similarity of their drug release profiles with the innovator. Hence, all the sampled cefuroxime axetil brands can be considered as pharmaceutical equivalents to the innovator drug. These brands can, therefore, be used as a substitute for the innovator drug by physicians to patients in cases of unaffordability or unavailability of the innovator brand.

Treatment of Impetigo and Antimicrobial Resistance.

BACKGROUND: Impetigo is a contagious bacterial infection that affects the superficial skin layers. Increasing worldwide antimicrobial resistance (AMR) to existing topical agents commonly prescribed to treat impetigo is central to treatment failure. The Worldwide Health Organization developed a global action plan on AMR, but omitted information about AMR stewardship programs for topical antibiotics. OBJECTIVES: The review aims to provide information to clinicians and stakeholders regarding AMR and antimicrobial stewardship on topical antimicrobial drugs for impetigo treatment. METHODS: The literature searches reviewed the status of AMR to current topical antibiotics in impetigo, current therapeutic behavior, and concordance with antimicrobial stewardship principles. Two international panels convened to discuss the output of the searches, and the results of the panel discussions were used in the development of the manuscript. RESULTS: The literature search included clinical trials, research studies, clinical guidelines, consensus papers, and reviews (if they provided original data), published between January 2008 and May 2019. The articles were selected based on clinical relevancy of impetigo management, clinical efficacy, and safety of the treatment and antimicrobial resistance. The searches resulted in one-hundred and ninety-eight articles. After applying the eligibility criteria, nineteen articles met inclusion criteria and were considered in the present review. CONCLUSIONS: While published antimicrobial stewardship guidelines have focused on systemic antibiotics, few studies have attempted to evaluate topical antibiotic prescribing practices for impetigo treatment. Many of the topical impetigo treatments currently in use have developed resistance. The appropriate use of topical ozenoxacin can help eradicate impetigo while minimizing AMR.J Drugs Dermatol. 20(4):366-372. doi:10.36849/JDD.5795.

Prophylaxis With Trimethoprim/Sulfamethoxazole Is Not Necessary in Children With Solid Tumors Treated With Low-medium Intensity Chemotherapy.

Prophylaxis of Pneumocystis jiroveci pneumonia (PJP) with trimethoprim/sulfamethoxazole is a standard of care for children with hematologic malignancies, while its use in solid tumor patients is still debated. A retrospective study focusing on the use of PJP prophylaxis in patients with solid tumors was performed among 16 AIEOP centers: 1046/2863 patients did not receive prophylaxis and no cases of PJP were reported.

1H nuclear magnetic resonance-based metabolite profiling of guava leaf extract: an attempt to develop a prototype for standardization of plant extracts.

BACKGROUND: Herbal medicines are fast gaining popularity. However, their acceptability by modern practitioners is low which is often due to lack of standardization. Several approaches towards standardization of herbals have been employed. The current study attempted to recognize key peaks from 1H NMR spectra which together would comprise of a spectral fingerprint relating to efficacy of Psidium guajava (guava) leaf extract as an antidiarrhoeal when a number of unidentified active principles are involved. METHODS: Ninety samples of guava leaves were collected from three locations over three seasons. Hydroalcoholic (water and ethanol, 50:50) extracts of these samples were prepared and their 1H NMR spectra were acquired. Spectra were also obtained for quercetin, ferulic acid and gallic acid as standards. Eight bioassays reflecting different stages of diarrhoeal pathogenesis were undertaken and based on pre-decided cut-offs, the extracts were classified as 'good' or 'poor' extracts. The bioactivity data was then correlated with the 1H NMR profiles using Regression or Orthogonal Partial Least Square-Discriminant Analysis (OPLS-DA). RESULTS: OPLS-DA showed seasonal and regional segregation of extracts. Significant models were established for seven bioassays, namely those for anti-bacterial activity against Shigella flexneri and Vibrio cholerae, adherence of E. coli, invasion of E. coli and S. flexneri and production and binding of toxin produced by V. cholerae. It was observed that none of the extracts were good or bad across all the bioassays. The spectral analysis showed multiple peaks correlating with a particular activity. Based on NMR and LC-MS/MS, it was noted that the extracts contained quercetin, ferulic acid and gallic acid. However, they did not correlate with the peaks that segregated extracts with good and poor activity. CONCLUSIONS: The current study identified key peaks in 1H NMR spectra contributing to the anti-diarrhoeal activity of guava leaf extracts. The approach of using spectral fingerprinting employed in the present study can thus be used as a prototype towards standardization of plant extracts with respect to efficacy.

A study of the microbiological profile of filler-induced skin necrosis.

Skin necrosis is one of the most severe complications following filler injections, and can result in permanent aesthetic defects. Although an increasing number of studies have addressed the management of dermal filler complications, no study has described the spectrum of microbial pathogens. The aim of this study was to delineate the bacterial profile and prognostic factors of filler-related skin necrosis by reviewing the clinical and microbiological features of these patients. A retrospective medical record review of patients undergoing treatment for skin necrosis induced by fillers was conducted. In total, 10 cases were identified, with injection sites being the nasolabial fold (70%; n = 7), nasal dorsum (20%; n = 2) and nasal tip (10%; n = 1). Reviewing the culture results, the true culture-positive rate was found to be 50% after cases of contamination were excluded. To avoid permanent sequelae, all physicians should be aware of possible secondary infections when treating filler-induced skin necrosis.

Intrapartum and Postpartum Management of Intra-amniotic Infection.

IMPORTANCE: Intra-amniotic infection (IAI) is a common condition with potentially devastating maternal and neonatal complications. However, there are incomplete data regarding the most effective antimicrobial treatment regimen for this condition. OBJECTIVE: This article aims to review the current evidence and recommendations for intrapartum and postpartum management of IAI. EVIDENCE ACQUISITION: Original research articles, review articles, and guidelines on IAI were reviewed. RESULTS: Numerous known risk factors for IAI exist, some of which are modifiable. Serious neonatal complications can result from exposure to IAI including increased risk of preterm birth and neonatal death. Possible maternal complications include increased risk of cesarean delivery, postpartum hemorrhage, and postpartum endometritis. Antibiotics are the mainstay of treatment for IAI for both mothers and neonates, although there is no consensus on which antimicrobial agents are best and the appropriate duration of therapy. CONCLUSIONS AND RELEVANCE: Monitoring patients for signs of IAI, proper treatment, and communication of the diagnosis with the pediatric team are essential for preventing maternal and neonatal complications of IAI. More research is needed to determine the proper treatment regimens for both mothers diagnosed with IAI and their neonates.

Analysis of risk factors, pathogenic bacteria of maternal sepsis in term pregnant women with positive blood culture during hospitalization.

ABSTRACT: The objective of this study was to evaluate the risk factors, pathogenic bacteria and drug sensitivity of maternal sepsis, and provide evidence for clinical prevention and treatment.A retrospective investigation of pregnant women with full-term maternal sepsis was performed to analyze the risk factors, pathogenic bacteria, and drug sensitivity of maternal sepsis.Univariate analysis showed that temperature, serum procalcitonin (PCT) and C-reactive protein (CRP) at admission, white blood cell count (WBC), PCT, CRP and neutrophilic granulocyte percentage (N%) during fever, premature rupture of membranes (PROM), antibiotic use within 1 week, mode of production, onset and duration of fever, between groups were statistically significant (P < .05). Logistic regression analysis showed that cesarean section was an independent risk factor for sepsis (OR = 11.839, 95%CI: 3.121-44.906). Apparent increase was found in body temperature (OR = 3.664, 95%CI: 1.722-7.795), duration of fever (OR = 1.953, 95%CI: 1.242-3.071), and PCT (OR = 1.080, 95%CI: 1.002-1.163). Also, increasing neutrophil ratio (OR = 1.180, 95%CI: 1.073-1.297) indicated a high possibility of maternal sepsis. The organism Escherichia coli (E. coli) was the most common pathogenic bacteria in the positive blood culture group (90%), and the sensitivity to carbapenems (meropenem and imipenem/cilastatin) was 100%, that to piperacillin-tazobactam and amoxicillin sulbactam was over 90%, and that to ceftazidime was 95%.Cesarean section was an independent risk factor for maternal sepsis in term pregnant women with positive blood culture. Besides, the E. coli was the most common pathogenic bacteria in the positive blood culture group. Antibiotics should be used in time and reasonably when the temperature was significantly increased with elevated PCT and N% after a cesarean section.

Airway Pseudomonas aeruginosa density in mechanically ventilated patients: clinical impact and relation to therapeutic efficacy of antibiotics.

BACKGROUND: The bacterial density of Pseudomonas aeruginosa is closely related to its pathogenicity. We evaluated the effect of airway P. aeruginosa density on the clinical course of mechanically ventilated patients and the therapeutic efficacy of antibiotics. METHODS: We retrospectively analyzed data of mechanically ventilated ICU patients with P. aeruginosa isolated from endotracheal aspirates. Patients were divided into three groups according to the peak P. aeruginosa density during ICU stay: low (≤ 104 cfu/mL), moderate (105‒106 cfu/mL), and high (≥ 107 cfu/mL) peak density groups. The relationship between peak P. aeruginosa density and weaning from mechanical ventilation, risk factors for isolation of high peak density of P. aeruginosa, and antibiotic efficacy were investigated using multivariate and propensity score-matched analyses. RESULTS: Four-hundred-and-sixty-one patients were enrolled. Patients with high peak density of P. aeruginosa had higher inflammation and developed more severe respiratory infections. High peak density of P. aeruginosa was independently associated with few ventilator-free days on day 28 (P < 0.01) and increased ICU mortality (P = 0.047). Risk factors for high peak density of P. aeruginosa were prolonged mechanical ventilation (odd ratio [OR] 3.07 95% confidence interval [CI] 1.35‒6.97), non-antipseudomonal cephalosporins (OR 2.17, 95% CI 1.35‒3.49), hyperglycemia (OR 2.01, 95% CI 1.26‒3.22) during ICU stay, and respiratory diseases (OR 1.9, 95% CI 1.12‒3.23). Isolation of commensal colonizer was associated with lower risks of high peak density of P. aeruginosa (OR 0.43, 95% CI 0.26‒0.73). Propensity score-matched analysis revealed that antibiotic therapy for patients with ventilator-associated tracheobronchitis improved weaning from mechanical ventilation only in the high peak P. aeruginosa group. CONCLUSIONS: Patients with high peak density of P. aeruginosa had worse ventilator outcome and ICU mortality. In patients with ventilator-associated tracheobronchitis, antibiotic therapy was associated with favorable ventilator weaning only in the high peak P. aeruginosa density group, and bacterial density could be a good therapeutic indicator for ventilator-associated tracheobronchitis due to P. aeruginosa.

Use of multiple metrics to assess antibiotic use in Italian children's hospitals.

Quantification of antibiotic utilization is an essential component of antibiotic stewardship programs. In this multicentric study, we used different metrics to evaluate inpatient antibiotic use in children. The study objectives were to describe point prevalence of antibiotic use by indication and patient characteristics, to evaluate DOTs, LOTs and PDDs, and to compare PDDs to DDDs, which assume average maintenance dose per day in adults. All children hospitalized on the days of the study were included. Trained personnel collected demographic and clinical data from patients' clinical records. We recorded information about antibiotics administered on the date of data collection, and in the previous 30 days of hospitalization. Of 810 patients, 380 (46.9%; CI 95%: 43.4-50.4) received one or more antibiotics; prevalence of use was 27.0% for prophylaxis (219/810), and 20.7% (168/810) for treatment. Overall, 587 drugs were issued to the 380 patients receiving antibiotics (1.5 antibiotic per patient). When considering treatments, DOT and LOT per 100 patient-days were 30.5 and 19.1, respectively, resulting in a DOT/LOT ratio of 1.6. PDDs increased with age and approached DDDs only in children aged ≥ 10 years; the ratio between PDDs estimated in children aged ≥ 10 years and in 0-11 month-old infants ranged from 2 for sulfamethoxazole and trimethoprim, to 25 for meropenem. Our results confirm that DOT, LOT and PDD are better alternatives to DDD in children.