Forecasting the long-term impact of COVID-19 on hepatitis C elimination plans in Italy: A mathematical modelling approach.

BACKGROUND: Italy has a high HCV prevalence, and despite the approval of a dedicated fund for 'Experimental screening' for 2 years, screening has not been fully implemented. We aimed to evaluate the long-term impact of the persisting delay in HCV elimination after the Coronavirus disease 2019 (COVID-19) pandemic in Italy. METHODS: We used a mathematical, probabilistic modelling approach evaluating three hypothetical 'Inefficient', 'Efficient experimental' and 'WHO Target' screening scenarios differing by treatment rates over time. A Markov chain for liver disease progression evaluated the number of active infections, decompensated cirrhosis (DC), hepatocellular carcinoma (HCC) and HCV liver-related deaths up to the years 2030 and 2050. RESULTS: The 'WHO Target' scenario estimated 3900 patients with DC and 600 with HCC versus 4400 and 600 cases, respectively, similar for both 'Inefficient' and 'Efficient experimental' screening up to 2030. A sharp (10-fold) decrease in DC and HCC was estimated by the 'WHO Target' scenario compared with the other two scenarios in 2050; the forecasted number of DC was 420 cases versus 4200 and 3800 and of HCC <10 versus 600 and 400 HCC cases by 'WHO Target,' 'Inefficient' and 'Efficient experimental' scenarios, respectively. A significant decrease of the cumulative estimated number of liver-related deaths was observed up to 2050 by the 'WHO Target' scenario (52000) versus 'Inefficient' or 'Efficient experimental' scenarios (79 000 and 74 000 liver-related deaths, respectively). CONCLUSIONS: Our estimates highlight the need to extensively and efficiently address HCV screening and cure of HCV infection in order to avoid the forecasted long-term HCV adverse outcomes in Italy.

Safety and effectiveness of 8 weeks of Glecaprevir/Pibrentasvir in challenging HCV patients: Italian data from the CREST study.

INTRODUCTION: Glecaprevir/pibrentasvir (G/P) has demonstrated high rates (>95%) of sustained virologic response at posttreatment Week 12 (SVR12) in treatment-naïve (TN) patients with hepatitis C virus (HCV) infection and compensated cirrhosis (CC). Here, in a key real-world subset of TN Italian patients with CC, we evaluated the effectiveness and safety of 8-week G/P treatment, including subgroups of interest such as those with genotype 3 (GT3) infection, elderly patients, and those with more advanced liver disease. METHODS: Subanalysis of Italian patients enrolled in the CREST study. The full analysis set (FAS) included all patients enrolled in the study; the modified analysis set (MAS) excluded patients who discontinued G/P for nonvirologic failure or who had missing SVR12 results. Primary and secondary endpoints included SVR12 and safety, respectively. RESULTS: Of 42 patients included in the FAS, 1 discontinued for unknown reasons, and 2 had missing SVR12 data, leaving 39 patients included in the MAS. At treatment initiation, 74% of patients had ≥1 comorbidity, and 62% were receiving concomitant medications, including some that may potentially interact with G/P. SVR12 was achieved in 100% of patients in the MAS, and in 95% in the FAS. In subgroups of interest, the proportion of patients achieving SVR12 in the MAS (and FAS) was: 100% (94%) for patients ≥65 years, 100% (86%) for GT3, and 100% (100%) for patients with platelet count <150 × 109/L and FibroScan® >20 kPa. Overall, 2 (5%) patients had an adverse event and neither were serious. CONCLUSION: Results from this real-world Italian cohort demonstrated the safety and effectiveness of 8-week G/P, with SVR12 rate >95%, even in elderly patients. These findings further support real-world evidence of the use of short-course G/P treatment in all patients with CC, including those with GT3, and those with advanced liver disease.

Prevalence of hepatitis C virus estimates of undiagnosed individuals in different Italian regions: a mathematical modelling approach by route of transmission and fibrosis progression with results up to January 2021.

This study provides an update on hepatitis C virus (HCV) estimates across Italy up to January 2021. A mathematical probabilistic modelling approach, including a Markov chain for liver disease progression, was used to estimate current HCV viraemic burden. Prevalence was defined by geographic area using an estimated annual historical HCV incidence by age, treatment, and migration rate from the Italian National database (ISTAT). Viraemic infection was estimated for the main HCV transmission routes by stages F0-F3 (patients without liver cirrhosis, i.e., potentially asymptomatic liver disease) and F4 (patients with liver cirrhosis, i.e., potentially symptomatic liver disease). By January 2021, we estimated that there were 398,610 individuals in Italy with active HCV infection (prevalence of 0.66%; 95% CI: 0.66-0.67), of which 287,730 (0.48%; 95% CI: 0.46-0.59%) were stage F0-F3. Prevalence values for all individuals with active HCV infection were: North 0.54% (95% CI: 0.53-0.54%), Central 0.88% (95% CI: 0.87-0.89%), South 0.72% (95% CI: 0.71-0.73%), and the Isles 0.67% (95% CI: 0.66-0.68%). The population at risk for previous/current drug injection accounted for 48.6% of all individuals with active HCV infection. A modelling approach such as this to estimate and update the prevalence of active HCV infection could be a useful methodology for the evaluation of healthcare policies related to HCV elimination plans.

Criteria for identification of advanced Parkinson's disease: the results of the Italian subgroup of OBSERVE-PD observational study.

BACKGROUND: Frequency of Advanced Parkinson's Disease (APD) and its clinical characteristics are still not well defined. Here, we aimed to assess APD prevalence in the Italian OBSERVE-PD cohort, as well as treatment eligibility to device-aided therapies (DAT), and to compare the APD clinical judgment with the established Delphi criteria. METHODS: This sub-group analysis of the OBSERVE-PD study was performed on patients enrolled by 9 Movement Disorders centers in Italy. Motor and non-motor symptoms, PD characteristics, activities of daily living, and quality of life were assessed. Patient eligibility for DAT, response to current PD treatments, referral process, and the concordance between APD physician's judgment and Delphi criteria were also assessed. RESULTS: According to physician's judgment, 60 out of 140 patients (43%) had APD. The correlation between physician's judgment and the overall APD Delphi criteria was substantial (K = 0.743; 95%CI 0.633-0.853), mainly driven by a discrete concordance found for the presence of ≥ 2 h of daily OFF time, presence of troublesome dyskinesia, ≥ 5 times daily oral levodopa dosing, and activities of daily living limitation. Forty-four (73%) APD patients were considered eligible to DAT but only 18 of them (41%) used these therapies, while most patients, independently from their eligibility, continued to use 3-5 oral daily medications, due to fear of invasive solutions and need to have a longer time to decide. CONCLUSION: APD was frequent in the Italian OBSERVE-PD population. DAT in the eligible APD population proved to be underused, in spite of unsatisfactory symptoms control with oral medications in 67% of patients.

A mathematical model by route of transmission and fibrosis progression to estimate undiagnosed individuals with HCV in different Italian regions.

BACKGROUND: Although an increase in hepatitis C virus (HCV) prevalence from Northern to Southern Italy has been reported, the burden of asymptomatic individuals in different Italian regions is currently unknown. METHODS: A probabilistic approach, including a Markov chain for liver disease progression, was applied to estimate current HCV viraemic burden. The model defined prevalence by geographic area using an estimated annual historical HCV incidence by age, treatment rate, and migration rate from the Italian National database. Viraemic infection by age group was estimated for each region by main HCV transmission routes of individuals for stage F0-F3 (i.e. patients without liver cirrhosis and thus potentially asymptomatic) and F4 (patients with liver cirrhosis, thus potentially symptomatic). RESULTS: By January 2020, it was estimated that there were 409,184 Italian individuals with HCV (prevalence of 0.68%; 95% CI: 0.54-0.82%), of which 300,171 (0.50%; 95% CI: 0.4-0.6%) were stage F0-F3. Considering all individuals with HCV in stage F0-F3, the geographical distributions (expressed as the proportion of HCV infected individuals by macroarea within the overall estimated number of F0-F3 individuals and prevalence values, expressed as the percentage of individuals with HCV versus the overall number of individuals for each macroarea) were as follows: North 42.1% (0.45%; 95% CI: 0.36-0.55%), Central 24.1% (0.61%; 95% CI: 0.48-0.74%), South 23.2% (0.50%; 95% CI: 0.4-0.61%), and the Isles 10.6% (0.49%; 95% CI: 0.39-0.59%). The population of people who inject drugs accounted for 50.4% of all individuals infected (F0-F3). Undiagnosed individuals (F0-F3) were ~ 15 years younger (⁓ 50 years) compared with patients with stage F4 (⁓ 65 years), with similar age distributions across macroareas. In contrast to what has been reported on HCV epidemiology in Italy, an increasing trend in the proportion of potentially undiagnosed individuals with HCV (absolute number within the F0-F3) from South (23.2%) to North (42.1%) emerged, independent of similar regional prevalence values. CONCLUSION: This targeted approach, which addresses the specific profile of undiagnosed individuals, is helpful in planning effective elimination strategies by region in Italy and could be a useful methodology for other countries in implementing their elimination plans.

Addressing HCV Elimination Barriers in Italy: Healthcare Resource Utilization and Cost Impact Using 8 Weeks' Glecaprevir/Pibrentasvir Therapy.

INTRODUCTION: In Italy, hepatitis C virus (HCV) elimination is achievable; however, barriers remain to achieving the World Health Organization's elimination targets, and have become more pronounced with the spread of COVID-19. Glecaprevir/pibrentasvir (G/P) is a direct-acting antiviral therapy for HCV, approved for 8-week treatment in patients without cirrhosis, and with compensated cirrhosis (CC). Previously, 12 weeks of therapy was recommended for patients with CC. Shortened treatment may reduce the burden on healthcare resources, allowing more patients to be treated. This study presents the benefits that 8-week vs 12-week treatment with G/P may have in Italy. METHODS: A multicohort Markov model was used to assess the collective number of healthcare visits and time on treatment with 8-week vs 12-week G/P in the HCV-infected population of Italy from 2019 to 2030, using healthcare resource data from post-marketing observational studies of G/P. Increased treatment capacity and downstream clinical and economic benefits were also assessed assuming the reallocation of saved healthcare visits to treat more patients. RESULTS: Modeled outcomes showed that by 2030, 8-week treatment saved 27,006 years on therapy compared with 12-week treatment, with 21,065 fewer hepatologist visits. Reallocating these resources to treat more patients could increase capacity to treat 5064 (1.4%) more patients with 8 weeks of G/P, all with CC. This increased treatment capacity would further avoid 2257 cases of end-stage liver disease, 893 liver-related deaths, and provide net savings to the healthcare system of nearly €70 million. CONCLUSION: The modeled comparisons between 8- and 12-week treatment with G/P show that shorter treatment duration can lead to greater time and resource savings, both in terms of healthcare visits and downstream costs. These benefits have the potential to enable the treatment of more patients to overcome elimination barriers in Italy through programs aimed to engage and treat targeted HCV populations.

Estimated prevalence of undiagnosed HCV infected individuals in Italy: A mathematical model by route of transmission and fibrosis progression.

BACKGROUND: The universal treatment of diagnosed patients with chronic HCV infection has been widely conducted in Italy since 2017. However, the pool of individuals diagnosed but yet to be treated in Italy has been estimated to end around 2025, leaving a significant proportion of infected individuals undiagnosed/without care. Estimates of this population are currently unknown. METHODS: A probabilistic modelling approach was applied to estimate annual historical HCV incident cases by their age-group (0-100 years) distribution from available literature and Italian National database (1952 to October 2019). Viraemic infection rates were modelled on the main infection routes in Italy: people who inject drugs (PWID), tattoos, sexual transmission, glass syringe use, blood transfusion and vertical transmission. Annual liver fibrosis stage transition probabilities were modelled using a Markov model. The number of HCV viraemic asymptomatic (fibrosis stage F0-F3:potentially undiagnosed/unlinked to care) and symptomatic (fibrosis stage F4: potentially linked to care) individuals was estimated. RESULTS: By October 2019, total viraemic HCV individuals in Italy (excluding treated patients since 1992) were estimated to be 410,775 (0.68 % of current population of Italy; 95 % CI: 0.64-0.71%, based on the current Italian population), of which 281,809 (0.47 %; 95 % CI:0.35-0.60%) were fibrosis stage F0-F3. Among different high risk groups in stage F0-F3, the following distribution was estimated: PWID; 52.0 % (95 % CI:37.9-66.6 %), tattoo; 28.8 % (95 % CI:23-32.3 %), sexual transmission; 12.0 % (95 % CI:9.6-13.7 %), glass syringe and transfusion; 6.4 % (95 % CI:2.4-17.8 %), and vertical transmission; 0.7 % (95 % CI:0.4-1.2 %). CONCLUSION: Under the assumption that most untreated HCV-infected individuals with stage F0-F3 are undiagnosed, more than 280,000 individuals are undiagnosed and/or unlinked to care in Italy. Marked heterogeneity across the major routes of HCV transmission was estimated. This modelling approach may be a useful tool to characterise the HCV epidemic profile also in other countries, based on country specific epidemiology and HCV main transmission routes.

Impact of the 2014 American Academy of Pediatrics recommendation and of the resulting limited financial coverage by the Italian Medicines Agency for palivizumab prophylaxis on the RSV-associated hospitalizations in preterm infants during the 2016-2017 epidemic season: a systematic review of seven Italian reports.

BACKGROUND: The only pharmacologic prophylaxis against respiratory syncytial virus (RSV) infection in preterm infants is the humanized monoclonal antibody palivizumab. After the 2014 modification of the American Academy of Pediatrics (AAP) recommendations, the Italian Medicines Agency (AIFA) limited the financial coverage for palivizumab prescriptions to otherwise healthy preterm infants with < 29 weeks of gestational age (wGA) aged < 12 months at the beginning of the 2016-2017 RSV season. However, due to the effect on disease severity and hospitalizations following this limitation, shown by several Italian clinical studies, in November 2017 AIFA reinstated the financial coverage for these infants. In this systematic review, we critically summarize the data that show the importance of palivizumab prophylaxis. METHODS: Data from six Italian pediatric institutes and the Italian Network of Pediatric Intensive Care Units (TIPNet) were retrieved from the literature and considered. The epidemiologic information for infants 29-36 wGA, aged < 12 months and admitted for viral-induced acute lower respiratory tract infection were retrospectively reviewed. RSV-associated hospitalizations were compared between the season with running limitation, i.e. 2016-2017, versus 2 seasons before (2014-2015 and 2015-2016) and one season after (2017-2018) the AIFA limitation. RESULTS: During the 2016-2017 RSV epidemic season, when the AIFA limited the financial coverage of palivizumab prophylaxis based on the 2014 AAP recommendation, the study reports on a higher incidences of RSV bronchiolitis and greater respiratory function impairment. During this season, we also found an increase in hospitalizations and admissions to the Pediatric Intensive Care Units and longer hospital stays, incurring higher healthcare costs. During the 2016-2017 epidemic season, an overall increase in the number of RSV bronchiolitis cases was also observed in infants born full term, suggesting that the decreased prophylaxis in preterm infants may have caused a wider infection diffusion in groups of infants not considered to be at risk. CONCLUSIONS: The Italian results support the use of palivizumab prophylaxis for otherwise healthy preterm (29-36 wGA) infants aged < 6 months at the beginning of the RSV season.

Observational study on the QUality of life of Italian Axial SpondyloARthritis patients (QUASAR): baseline data.

OBJECTIVES: To describe the baseline characteristics of the patients enrolled in the QUality of life in patients with Axial SpondyloARthritis (QUASAR) study in terms of quality of life (QoL), disease activity, therapy adherence, and work ability in a real-world setting. METHODS: QUASAR is an Italian multicentre, prospective 12-month observational study, including consecutive adult patients classified as axial spondyloarthritis (axSpA) according to the Assessment of SpondyloArthritis international Society criteria for axSpA. RESULTS: Of 512 patients enrolled in 23 rheumatology centres, 80.7% had ankylosing spondylitis (AS) and 19.3% had non-radiographic axSpA (nr-axSpA). Mean ages were 34.1±13.3 years at axSpA symptoms onset and 39.5±13.0 years at diagnosis. Of the patients, 51.4% presented with ≥1 extra articular manifestation (EAM); the most common were psoriasis (17.8%) and uveitis (16.4%). Patients with nr-axSpA and AS had similar EAM rates, disease activity, and QoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs; 83.2%) were the most commonly received medication, followed by conventional synthetic DMARDs (22.9%) and non-steroidal anti-inflammatory drugs (NSAIDs; 16.6%). At baseline, higher treatment satisfaction was reported with bDMARDs which, together with NSAIDs, were associated with the best overall scores for disease activity, function, and QoL in the overall population and AS subgroup. CONCLUSIONS: QUASAR is the first Italian prospective study that comprehensively evaluated a large axSpA patient sample in a real-world setting. This interim analysis at baseline confirmed that i) patients with AS and nr-axSpA have similar QoL and disease burden, ii) nearly all axSpA patients receive treatment, and iii) bDMARDs and NSAIDs, overall, yield better disease activity and QoL.

Ultrasonographic and Clinical Assessment of Peripheral Enthesitis in Patients with Psoriatic Arthritis, Psoriasis, and Fibromyalgia Syndrome: The ULISSE Study.

OBJECTIVE: The purpose of the ULISSE study was to evaluate the prevalence of clinical and ultrasonographic (US) entheseal involvement in patients with psoriatic arthritis (PsA), psoriasis, and fibromyalgia syndrome (FMS). METHODS: In this cross-sectional multicenter study, patients with PsA and psoriasis (not taking systemic therapy) and FMS underwent a clinical evaluation of the entheses, and a B-mode and power Doppler examination of 6 pairs of entheses. RESULTS: The study analyzed 140 patients with PsA, 51 with psoriasis, and 51 with FMS. Clinical and US examinations were performed in 1960 and 1680 entheses in the PsA group, and 714 and 612 entheses both in the psoriasis group and in the FMS group. In both per-patient and per-enthesis evaluation, the frequency of entheseal tenderness was higher in patients with FMS (92% of the patients and 46% of the entheses, compared with 66%/23% in the PsA group and 59%/18% in the psoriasis group). With US examination, signs of entheseal involvement were more frequent in both the per-patient and per-enthesis evaluation in PsA and psoriasis (about 90% of patients in both the PsA and psoriasis groups and 75% of patients in the FMS group had at least 1 site affected, and 54%, 41%, and 27% of the pairs of entheses in, respectively, PsA, psoriasis, and FMS patients showed at least 1 enthesis involved). CONCLUSION: The ULISSE study indicated that enthesitis is a common feature in patients with PsA, those with psoriasis, and in those with FMS if only clinical examination is used. US entheseal assessment showed findings more consistent with the 3 disorders.

Epidemiological features and disease-related concerns of a large cohort of Italian patients with active Crohn's disease.

BACKGROUND-AIMS: The SOLE study was conducted on a large cohort of Italian patients with moderate-severe Crohn's disease (CD) to assess epidemiological and disease characteristics and their correlation with disease-related worries, treatment satisfaction and adherence, workability. METHODS: The following tools were used over 12 months to assess: Results were correlated with demographic and clinical variables with linear regression models. RESULTS: 552 patients with active CD (51% men) were recruited. Higher worries were having an ostomy bag and undergoing surgery. Variables associated with a higher RFIPC score included female sex, higher disease activity, lower treatment adherence (p < 0.001), previous surgical treatments (p = 0.003). 60% of patients claimed difficulties with activities of daily living. Lower VAS scores were reported by patients with disease duration >6years; treatment satisfaction/adherence was higher with anti-TNF-α treatment. Decreased hospitalizations during follow-up and improved workability/daily activities occurred with adalimumab, infliximab, azathioprine (p < 0.001). CONCLUSION: Worries included having an ostomy bag, undergoing surgery, developing cancer: conditions significantly associated with worsened disease activity and low treatment adherence. Higher treatment adherence scores/greater workability improvements were observed in patients treated with anti-TNF-α agents.

Risk factors for severe RSV-induced lower respiratory tract infection over four consecutive epidemics.

UNLABELLED: Variability in severity among different respiratory syncytial virus (RSV) seasons may influence hospital admission rates for RSV-induced lower respiratory tract infection (LRTI) in young children. The aim of the present study was to identify through logistic regression analysis, risk factors associated with higher likelihood to acquire RSV-induced LRTI, in children with symptoms severe enough to lead to hospital admission. Over four consecutive RSV seasons (2000-2004), records from children <4 years of age admitted for RSV-induced LRTI ("cases") were compared with those from children with LRTI not due to RSV and not requiring hospitalization ("controls"). 145 "case-patients" and 295 "control-patients" were evaluated. Independent from the severity of the four epidemic seasons, seven predictors for hospitalization for RSV infection were found in the bivariate analysis: number of children in the family, chronological age at the onset of RSV season, birth weight and gestational age, birth order, daycare attendance, previous RSV infections. In the logistic regression analysis, only three predictors were detected: chronological age at the beginning of RSV season [aOR =8.46; 95% CI:3.09-23.18]; birth weight category [aOR =7.70; 95% CI:1.29-45.91]; birth order (aOR =1.92; 95% CI:1.21-3.06). CONCLUSIONS: Independent from the RSV seasonality, specific host/environmental factors can be used to identify children at greatest risk for hospitalization for RSV infection.

Four year incidence of respiratory syncytial virus infection in infants and young children referred to emergency departments for lower respiratory tract diseases in Italy: the "Osservatorio VRS" Study (2000-2004).

Respiratory Syncytial Virus (RSV) is a frequent cause of hospital admission in young children and high risk babies such as premature newborns, or babies with underlying cardiac or pulmonary disease, or immunodeficiency. Outbreaks occur most frequently in the cold season in areas with temperate and Mediterranean climates. Aim of the "Osservatorio VRS" Study was to describe the time-related pattern of RSV epidemics in Italy, across four consecutive epidemics, from 2000 to 2004. Nasal specimens for RSV detection were obtained and tested by an immunoenzymatic test. A total of 2110 children were tested for RSV determination, the rate of children with RSV infection was 21%, and that of children hospitalized for RSV disease was 49%. Considering the whole study period, the RSV epidemics started in October-November and ended in May, showing a peak incidence in February, with a median of 28.1% and a maximum of 48.9%. Analysis of monthly distribution of each year of the study showed a biennial trend for an earlier appearance. A different epidemiological pattern of the infection was observed among the three national areas. In conclusion, even though the mechanism governing RSV infection periodicity remains unknown, its awareness in the absence of an RSV surveillance system as in Italy, may be useful for scheduling RSV prophylaxis and for hospital resource management.

Incidence of respiratory syncytial virus infection in infants and young children referred to the emergency departments for lower respiratory tract diseases in Italy.

BACKGROUND: Respiratory Syncytial Virus (RSV) is the leading cause of emergency visits and hospitalization for acute lower respiratory tract infections (LRTI) in infants and young children worldwide. To collect specific epidemiological data on the incidence of RSV infection among infants referred to Emergency Departments (ED) for LRTI in a Mediterranean country, an Italian multicenter epidemiological surveillance program was established. METHODS: Eight pediatric centers throughout Italy participated in this study. The study population included 272 children < or =4 years of age, admitted to the ED between October 2000 and April 2001 for respiratory problems that might be possibly related to LRTI. 152 children were <1 year of age, 50 between 1 and 2 years, and 70 >2 years of age. Data regarding medical history and physical examination were recorded for each child, whereas an immunoenzymatic RSV test (TestPack RSV, Abbott) was performed on nasal and pharyngeal secretions. RESULTS: Out of 272 tested children, 85 were positive for RSV. The peak of the RSV epidemic occurred in February, with an earlier start and end of the RSV season in the northern and central regions, compared to the southern regions. Major risk factors for RSV infection were younger age (p<0.05) and low weight at birth (p<0.05). Among children positive for RSV infection, 55.2% were <1 year of age, 18.3% were between 1 and 2 years, and 25.7% were > 2 years of age. RSV positivity was associated with a higher rate of hospitalization in the whole study population (p<0.01) and especially in the children < or =12 months of age (p<0.01). Clinical evidence of lower respiratory tract involvement, was also more frequently observed in RSV positive than in RSV negative children, both in the whole study population (p<0.01) and in the < or =12 months of age subgroup (p<0.01). CONCLUSION: These data confirm that the patterns of RSV infection in Italy are similar to those reported for other countries in the northern hemisphere: RSV is associated with a higher risk of hospitalization and clinically evident LRTI involvement than respiratory infections of other etiologies, especially in infants.

Antimicrobial susceptibility of Streptococcus pneumoniae from children attending day-care centers in a central Italian city.

OBJECTIVE: To undertake a survey of nasopharyngeal carriage of Streptococcus pneumoniae, which reflects strains causing infection, in 100 children under 3 years of age attending day-care centers in Frosinone, a city near Rome. METHODS: Fifty-three unique isolates of S. pneumoniae, isolated from 41 of the children tested, were tested for antimicrobial susceptibility to penicillin, cefotaxime, erythromycin, clindamycin, tetracycline, chloramphenicol and trimethoprim---sulfamethoxazole. RESULTS: Resistance rates were as follows: penicillin, 20.7% (15% intermediate; 5.7% resistant); trimethoprim---sulfamethoxazole, 64.2%; erythromycin, 64.2%; clindamycin, 30.2%; tetracycline, 32.1%; and chloramphenicol, 3.8%. Except for three intermediate strains, all strains were susceptible to cefotaxime. Only five strains were susceptible to all of the antibiotics tested. An unusual finding of this study was that 23 of the 34 erythromycin-resistant strains were penicillin susceptible, whereas erythromycin-resistant strains found in other countries are predominantly penicillin resistant as well. In addition, 18 of the 34 erythromycin-resistant strains were susceptible to clindamycin. Serogroups 6, 14, 19 and 23 accounted for 84.9% of the isolates. CONCLUSIONS: These data show that carriage of antibiotic-resistant pneumococci in children under 3 years of age is high in Frosinone, Italy. Information on resistance rates in pneumococcal disease in different age groups and on prevalence of drug resistance in other parts of the country is urgently needed.