Expressions of Type I and III Interferons, Endogenous Retroviruses, TRIM28, and SETDB1 in Children with Respiratory Syncytial Virus Bronchiolitis.

Interferons (IFNs) and IFN-stimulated genes (ISGs) play essential roles for the control of viral infections. Their expression in infants with respiratory syncytial virus (RSV) bronchiolitis is poorly defined. Human endogenous retroviruses (HERVs) represent 8% of our genome and modulate inflammatory and immune reactions. TRIM28 and SETDB1 participate in the epigenetic regulation of genes involved in the immune response, including IFNs and HERVs. No study has explored the expression of HERVs, TRIM28, and SETDB1 during RSV bronchiolitis. We assessed, through a PCR real-time Taqman amplification assay, the transcription levels of six IFN-I ISGs, four IFNλs, the pol genes of HERV-H, -K, and -W families, the env genes of Syncytin (SYN)1 and SYN2, and of TRIM28/SETDB1 in whole blood from 37 children hospitalized for severe RSV bronchiolitis and in healthy children (HC). The expression of most IFN-I ISGs was significantly higher in RSV+ patients than in age-matched HC, but it was inhibited by steroid therapy. The mRNA concentrations of IFN-λs were comparable between patients and age-matched HC. This lack of RSV-driven IFN-III activation may result in the defective protection of the airway mucosal surface leading to severe bronchiolitis. The expression of IFN-III showed a positive correlation with age in HC, that could account for the high susceptibility of young children to viral respiratory tract infections. The transcription levels of every HERV gene were significantly lower in RSV+ patients than in HC, while the expressions of TRIM28/SETDB1 were overlapping. Given the negative impact of HERVs and the positive effects of TRIM28/SETDB1 on innate and adaptive immune responses, the downregulation of the former and the normal expression of the latter may contribute to preserving immune functions against infection.

Meningitis-retention syndrome: a review and update of an unrecognized clinical condition.

OBJECTIVES: We summarized the clinical and radiological characteristics of meningitis-retention syndrome (MRS), its therapeutic options, and urological outcome, to better understand the pathogenesis of this syndrome and to evaluate the effectiveness of corticosteroids in reducing the period of urinary retention. METHODS: We reported a new case of MRS in a male adolescent. We also reviewed the previously 28 reported cases of MRS, collected from inception up to September 2022. RESULTS: MRS is characterized by aseptic meningitis and urinary retention. The mean length of the interval between the onset of the neurological signs and the urinary retention was 6.4 days. In most cases, no pathogens were isolated in cerebrospinal fluid, except for 6 cases in which Herpesviruses were detected. The urodynamic study resulted in a detrusor underactivity, with a mean period for urination recovery of 4.5 weeks, regardless of therapies. DISCUSSION: Neurophysiological studies and electromyographic examination are not pathological, distinguishing MRS from polyneuropathies. Although there are no encephalitic symptoms or signs, and the magnetic resonance is often normal, MRS may represent a mild form of acute disseminated encephalomyelitis, without radiological detectable medullary involvement, due to the prompt use of steroids. It is believed that MRS is a self-limited disease, and no evidence suggests the effectiveness of steroids, antibiotics, and antiviral treatment in its clinical course.

Antimicrobial stewardship experience in paediatrics: first-year activity report.

Antimicrobial resistance is one of the most relevant threats in public health worldwide. Strategies as antimicrobial stewardship programs, aiming to preserve our antibiotic armamentarium, have been implemented since 2007 in adult and paediatric patients. We aim to describe the first experience of a paediatric antimicrobial stewardship program. We conducted a retrospective observational study in a tertiary care children's hospital. A team composed of a microbiologist, an infectious diseases physician, and a paediatrician led the project. All positive blood and cerebrospinal fluid cultures and other biological samples yielding multi-drug-resistant bacteria were collected and reviewed through a prospective-audit-with-feedback strategy. We recorded patient characteristics and worth monitoring prescribed antibiotics. The antimicrobial stewardship audit could end in intervention (step-up/step-down and broadening/narrowing) or recommendation(s). We then checked out wards staff compliance. The team performed 192 interventions out of 584 reviews, mostly suggesting discontinuation of antibiotics (in 76.0% of cases and 39.7% of running molecules). The antibiotic spectrum was more likely tapered than expanded (p < 0.0001), and we ordered more narrow-spectrum antibiotic molecules than local medical staff straightaway did (p = 0.0113). Interventions were most likely needed in case of documented infections (p < 0.0001) and in surgical patients (p = 0.0002). In 85.9% of interventions, ward teams fully agreed with our argument. This study demonstrated an antimicrobial stewardship program to be a suitable method for improving the appropriateness of antimicrobial use in hospitalized children.

COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases.

Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. TRIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children and in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19 children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection.

Detection of faecal SARS-CoV-2 RNA in a prospective cohort of children with multisystem inflammatory syndrome (MIS-C).

BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but severe illness associated with SARS-CoV-2 infection. A dysregulated immune response is recognized as the main pathogenic mechanism. Previous studies demonstrated the presence of SARS-CoV-2 RNA in faeces of almost one-third of patients with COVID-19, while data are currently missing about MIS-C. OBJECTIVES: to evaluate faecal sample positivity to SARS-CoV-2 in MIS-C and to compare the positivity rate between MIS-C and COVID-19 hospitalised children.  DESIGN: observational descriptive study with prospective patient enrollment. SETTING AND PARTICIPANTS: the SARS-CoV-2 positivity was evaluated in stool samples obtained in a prospective series of 63 paediatric patients admitted to Regina Margherita Children's Hospital (Azienda Ospedaliero Universitaria - Città della Salute e della Scienza, Turin, Northern Italy) with diagnosis of MIS-C (N. 31) or COVID-19 (N. 32), during the first year of pandemic emergency. The real-time reverse transcription polymerase chain reaction (real-time RT-PCR), was performed using a validated kit measuring 3 target SARS-CoV-2 genes: E gene, N gene, and ORF1ab gene MAIN OUTCOME MEASURES: SARS-CoV-2 stool positivity and concomitant gastrointestinal symptoms. RESULTS: overall, 16/63 (25%) stool samples revealed the presence of SARS-CoV-2 mRNA. In patients with COVID-19, faecal samples were collected 8 days as median (IQR 7) after the presumed viral exposure and were positive in 12/31 (39%; 95%CI 23.2-56.2); among children with MIS-C, stools were collected 27.5 days as median (IQR 26.25) after presumed contact and the positivity rate was 12.5% (95%CI 4.4-27.0) (4/32). More than 80% of the children with MIS-C presented gastrointestinal symptoms, but the frequency of gastrointestinal symptoms in patients with positive stools for SARS-CoV-2 RNA is not higher than patients tested negative (p=0.092). CONCLUSIONS: MIS-C patients frequently experienced gastrointestinal symptoms, confirming the intestinal involvement in MIS-C already described in the literature. The presence of SARS-CoV-2 mRNA in faecal samples is confirmed in more than 10% of MIS-C patients and stool positivity was also detected many days after presumed first contact with the virus. This data suggests the possibility of tracing SARS-COV-2 also in faeces for a better description of its circulation and spread in the environment.

Safety of Sotrovimab use in children with COVID-19: an Italian experience.

Sotrovimab is a monoclonal antibody approved in adult and adolescents at high risk for COVID-19. Thirty-three children evaluated in five Italian paediatric centres received Sotrovimab infusion and were retrospectively enrolled from December 2021 to April 2022. In more than half of cases (19/33, 57.6%) Sotrovimab was prescribed off-label. Overall, the infusion was well tolerated with no significative differences in those receiving an off-label prescription. All children had a complete recovery. Data on the safety of Sotrovimab should be investigated in a larger paediatric cohort, considering the continuous selection of new SARS CoV-2 variants which may be more or less susceptible to the effects of the Sotrovimab.

Long COVID-19/post-COVID condition in children: do we all speak the same language?

Post-COVID condition is a new and highly debated entity that is still to be outlined in its complexity, especially in the pediatric population. In response to the article by Trapani and colleagues, we report the results of a long-term follow-up conducted in the outpatient clinic of the Pediatric Infectious Diseases Unit on children admitted to our hospital with SARS-CoV-2 infection.

A Neuropsychiatric Assessment of Children with Previous SARS-CoV-2 Infection.

AIM: Concerns have been raised about possible neuropsychiatric sequelae of COVID-19. The objective of this study was to examine the plausibility of long-term mental health consequences of COVID-19 by assessing a sample of children after the resolution of the acute SARS-CoV-2 infection. METHOD: As part of a systematic follow-up assessment of pediatric patients with COVID-19 conducted at two university children's hospitals, 50 children (56% males) aged 8 to 17 years (median 11.5), 26% with previous multisystem inflammatory syndrome in children (MIS-C), without a prior history of neuropsychiatric disorders, received a battery of clinical neuropsychiatric and neuropsychological rating scales that included the Pediatric Migraine Disability Assessment (PedMIDAS), Sleep Disturbance Scale for Children (SDSC), Multidimensional Anxiety Scale for Children (MASC-2), Child Depression Inventory (CDI-2), Child Behavior Checklist (CBCL), and the NEPSY II (Neuropsychological Assessment, Second Edition). The assessments were conducted between 1 and 18 months (median 8 months) after the acute infection. RESULTS: The CBCL internalizing symptoms score was in the clinical range for 40% of the participants (vs. a population expected rate of about 10%, p < 0.001). A sleep disturbance was detected in 28%, clinically significant anxiety in 48%, and depressive symptoms in 16%. The NEPSY II scores showed impairment in attention and other executive functions in 52%, and memory deficits in 40% of the children. CONCLUSIONS: These data from direct assessment of a sample of children who had SARS-CoV-2 infection show higher than expected rates of neuropsychiatric symptoms, thus supporting the possibility that COVID-19 may have mental health sequelae long after the resolution of the acute infection.

The Importance of RSV Epidemiological Surveillance: A Multicenter Observational Study of RSV Infection during the COVID-19 Pandemic.

The restrictive measures adopted worldwide against SARS-CoV-2 produced a drastic reduction in respiratory pathogens, including RSV, but a dramatic rebound was thereafter reported. In this multicenter retrospective observational study in 15 Pediatric Emergency Departments, all children <3 years old with RSV infection admitted between 1 September and 31 December 2021 were included and compared to those admitted in the same period of 2020 and 2019. The primary aim was to evaluate RSV epidemiology during and after the COVID-19 pandemic peak. The secondary aims were to evaluate the clinical features of children with RSV infection. Overall, 1015 children were enrolled: 100 in 2019, 3 in 2020 and 912 in 2021. In 2019, the peak was recorded in December, and in 2021, it was recorded in November. Comparing 2019 to 2021, in 2021 the median age was significantly higher and the age group 2-3 years was more affected. Admissions were significantly higher in 2021 than in 2020 and 2019, and the per-year hospitalization rate was lower in 2021 (84% vs. 93% in 2019), while the duration of admissions was similar. No difference was found in severity between 2019-2020-2021. In conclusion, after the COVID-19 pandemic, an increase in RSV cases in 2021 exceeding the median seasonal peak was detected, with the involvement of older children, while no difference was found in severity.

Imported malaria in children: A 13 years retrospective study.

Malaria is not endemic in Italy, however every year about 600-700 imported cases are detected in people born or living in Italy who return from a stay in their country of origin (visiting friends and relatives - VFR). Children account for 20% of this population and they have an higher risk of severe disease. Socio-economic problems and deficiencies in the doctor-patient relationship often lead to a lack of awareness of the importance of prophylaxis, making the category of VFRs at increased risk of disease. The aim of this study is to analyze the characteristics of pediatric imported malaria, with a specific focus on prevention and risk factors for severe malaria. All malaria cases diagnosed from 2007 to 2019 in Ospedale Infantile Regina Margherita in Turin were retrospectively observed. Epidemiological and clinical data were described. A total of 72 patients were reported: 98.6% had African origins and 73.6% traveled as VFRs. Plasmodium falciparum was the species most commonly isolated (94.4%). Twenty-four patients (33.3%) underwent chemoprophylaxis and never appropriately. Patients not undergoing prophylaxis and those undergoing incomplete prophylaxis showed not statistically significant difference in term of disease severity (p = 0.26). Nineteen cases were considered severe, including 3 with cerebral malaria. High levels of parasitemia were statistically significantly correlated with severe anemia (p = 0.049) and severe thrombocytopenia (p = 0.036). In 25% of cases the first diagnosis was incorrect. The therapeutic use of artemisinin derivatives has resulted in a significant shortening of the parasitemia clearance time compared to the use of other drugs (p < 0.001). Families have to be educated about the serious implications of a malaria infection and the importance of a correct and complete prophylaxis. Clinicians should always consider malaria in the differential diagnoses in patients with fever and a history of a recent travel to an endemic area. Prompt diagnosis and use of appropriate drugs, according to the latest guidelines, could guarantee a better outcome for patients.

Intrapartum use of zidovudine in a large cohort of pregnant women living with HIV in Italy.

BACKGROUND: Intravenous administration of zidovudine (ZDV) during labour is a key step for vertical HIV transmission (VT) prevention, but there is no evidence of benefit when maternal HIV-RNA at delivery is <50 copies/mL. The aim of this study is evaluating the appropriateness of intrapartum ZDV use in Italy. METHODS: Observational study including mother-infant pairs with perinatal HIV exposure during 2002-2019, enrolled in the Italian Register for HIV Infection in Children. Univariable and multivariable logistic regression were used to evaluate factors associated with VT. RESULTS: A total of 3,861 infants, born from 3,791 pregnancies were included. The frequency of ZDV use was 79.9%, 92.1%, 93.7% and 92.8% when HIV-RNA was not available, ≥400 copies, between 50 and 399 copies, and <50 copies/mL. Thirty-three out of 3861 (0.85%) infants were subsequently diagnosed with HIV, 25/3861 (0.6%) of them born to mothers receiving intrapartum ZDV, and 31 (93.9%) to mothers with HIV-RNA ≥50 copies/mL or not available. In women with HIV-RNA < 50 copies/mL, ART discontinuation during pregnancy was the strongest risk factor for VT (odds ratio, OR, 23.1, 95%CI 2.4-219.3), while a higher gestational age (OR 0.6, 95%CI 0.4-0.8) and PEP administration to the newborn (aOR 0.004, 95%CI <0.0001-0.4) were protective factors. Intrapartum ZDV administration did not influence the final outcome in this group. CONCLUSIONS: In ART era, more transmission events may occur in utero, limiting value of intrapartum ZDV, particularly for women with suppressed HIV-RNA load. More attention to the HIV-RNA testing of mothers before delivery may avoid unnecessary ZDV use.

COVID-19 in Infants Less than 3 Months: Severe or Not Severe Disease?

Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature. Methods: Subjects under 90 days of age admitted to 35 Italian institutions for COVID-19 were included. The severity of COVID-19 was scored as mild/moderate or severe/critical following the classification reported in the literature by Venturini, Dong, Kanburoglu, and Gale. To assess the diagnostic accuracy of each classification system, we stratified all enrolled patients developing a posteriori severity score based on clinical presentation and outcomes and then compared all different scores analyzed. Results: We included 216 infants below 90 days of age. The most common symptom was fever, followed by coryza, poor feeding, cough, and gastrointestinal manifestations. According to Venturini, Dong, Kanburoglu, and Gale's severity scores, 18%, 6%, 4.2%, and 29.6% of infants presented with severe/critical disease, respectively. A correlation analysis between these four scores and the a posteriori severity score assigned to all enrolled subjects was performed, and a crescent strength of correlation from Gale (R = 0.355, p < 0.001) to Venturini (R = 0.425, p < 0.001), Dong (R = 0.734, p < 0.001), and Kanburoglu (R = 0.859, p < 0.001) was observed. Conclusions: The percentage of infants with severe COVID-19 varies widely according to the score systems. A unique clinical score should be designed for neonates and infants with COVID-19.

Corrigendum: MIS-C Treatment: Is IVIG Always Necessary?

[This corrects the article DOI: 10.3389/fped.2021.753123.].

MIS-C Treatment: Is IVIG Always Necessary?

Background: MIS-C is a potentially severe inflammatory syndrome associated with SARS-CoV-2 exposure. Intravenous immunoglobulin (IVIG) is considered the first-tier therapy, but it implies infusion of large fluid volumes that may worsen cardiac function. Patients and Methods: Since April 2020, we have developed a treatment protocol that avoids the infusion of IVIG as first-line therapy in the early phase of MIS-C. In this study, we retrospectively analyzed a cohort of consecutive patients treated according to this protocol between 01/04/2020 and 01/04/2021. Results: In the last year, 31 patients have been treated according to the protocol: 25 with high-dose pulse MP (10 mg/kg) and 6 with 2 mg/kg. 67.7% of the patients responded to the initial treatment, while the others needed a step-up, either with Anakinra (25.8%) or with MP dose increase (6.5%). IVIG was administered in four patients. Overall, only one patient (3.2%) needed ICU admission and inotropic support; one patient developed a small coronary artery aneurysm. Conclusions: Timely start of MP therapy and careful fluid management might improve the outcomes of MIS-C patients.

Association of Ethnicity With Multisystem Inflammatory Syndrome in Children Related to SARS-CoV-2 Infection: An International Case-Referent Study.

Background: It has been suggested that children and infants can develop multisystem inflammatory syndrome in children (MIS-C) in response to a SARS-CoV-2 infection and that Black children are overrepresented among cases. The aim of the current study was to quantify the association between Black, Asian, or other non-White genetic background and COVID-19-related MIS-C in children and infants. Methods: Eight different research groups contributed cases of MIS-C, potentially related to SARS-CoV-2 infection. Several sensitivity analyses were performed, including additional data available from the literature. Analyses were stratified by geographical region. Results: Seventy-three cases from nine distinct geographical regions were included in the primary analyses. In comparison to White children, the relative risk for developing MIS-C after SARS-CoV-2 infection was 15 [95% confidence interval (CI): 7.1 to 32] for Black children, 11 (CI: 2.2 to 57) for Asian, and 1.6 (CI: 0.58 to 4.2) for other ethnic background. Conclusion: Pediatricians should be aware of the fact that the risk of COVID-19-related MIS-C is severely increased in Black children.

First diagnosis of multisystem inflammatory syndrome in children (MIS-C): an analysis of PoCUS findings in the ED.

Children with multisystem inflammatory syndrome (MIS-C) tend to develop a clinical condition of fluid overload due both to contractile cardiac pump deficit and to endotheliitis with subsequent capillary leak syndrome. In this context, the ability of point-of-care ultrasound (PoCUS) to simultaneously explore multiple systems and detect polyserositis could promote adequate therapeutic management of fluid balance. We describe the PoCUS findings in a case-series of MIS-C patients admitted to the Emergency Department. At admission 10/11 patients showed satisfactory clinical condition without signs and symptoms suggestive for cardiovascular impairment/shock, but PoCUS showed pathological findings in 11/11 (100%). In particular, according to Rapid Ultrasound in SHock (RUSH) protocol, cardiac hypokinesis was detected in 5/11 (45%) and inferior vena cava dilatation in 3/11 (27%). Peritoneal fluid was reported in 6/11 cases (54%). Lung ultrasound (LUS) evaluation revealed an interstitial syndrome in 11/11 (100%), mainly localized in posterior basal lung segments. We suggest PoCUS as a useful tool in the first evaluation of children with suspected MIS-C for the initial therapeutic management and the following monitoring of possible cardiovascular deterioration.

SARS-COV-2-associated coagulopathy and thromboembolism prophylaxis in children: A single-center observational study.

BACKGROUND: Multiple investigators have described an increased incidence of thromboembolic events in SARS-CoV-2-infected individuals. Data concerning hemostatic complications in children hospitalized for COVID-19/multisystem inflammatory syndrome in children (MIS-C) are scant. OBJECTIVES: To share our experience in managing SARS-CoV-2-associated pro-coagulant state in hospitalized children. METHODS: D-dimer values were recorded at diagnosis in children hospitalized for SARS-CoV-2-related manifestations. In moderately to critically ill patients and MIS-C cases, coagulation and inflammatory markers were checked at multiple time points and median results were compared. Pro-thrombotic risk factors were appraised for each child and thromboprophylaxis was started in selected cases. RESULTS: Thirty-five patients were prospectively enrolled. D-dimer values did not discriminate COVID-19 of differing severity, whereas were markedly different between the COVID-19 and the MIS-C cohorts. In both cohorts, D-dimer and C-reactive protein levels increased upon clinical worsening but were not accompanied by decreased fibrinogen or platelet values, with all parameters returning to normal upon disease resolution. Six patients had multiple thrombotic risk factors and were started on pharmacological thromboprophylaxis. No deaths or thrombotic or bleeding complications occurred. CONCLUSIONS: COVID-19 pediatric patients show mildly altered coagulation and inflammatory parameters; on the other hand, MIS-C cases showed laboratory signs of an inflammatory driven pro-coagulant status. Universal anticoagulant prophylaxis in hospitalized children with SARS-CoV-2-related manifestations is not warranted, but may be offered to patients with other pro-thrombotic risk factors in the context of a multi-modal therapeutic approach.

Epidemiology, Clinical Features and Prognostic Factors of Pediatric SARS-CoV-2 Infection: Results From an Italian Multicenter Study.

Background: Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear and optimal treatment is debated. The objective of our study was to investigate epidemiological, clinical and therapeutic characteristics of pediatric SARS-CoV-2 infection, focusing on risk factors for complicated and critical disease. Methods: The present multicenter Italian study was promoted by the Italian Society of Pediatric Infectious Diseases, involving both pediatric hospitals and general pediatricians/family doctors. All subjects under 18 years of age with documented SARS-CoV-2 infection and referred to the coordinating center were enrolled from March 2020. Results: As of 15 September 2020, 759 children were enrolled (median age 7.2 years, IQR 1.4; 12.4). Among the 688 symptomatic children, fever was the most common symptom (81.9%). Barely 47% of children were hospitalized for COVID-19. Age was inversely related to hospital admission (p < 0.01) and linearly to length of stay (p = 0.014). One hundred forty-nine children (19.6%) developed complications. Comorbidities were risk factors for complications (p < 0.001). Viral coinfections, underlying clinical conditions, age 5-9 years and lymphopenia were statistically related to ICU admission (p < 0.05). Conclusions: Complications of COVID-19 in children are related to comorbidities and increase with age. Viral co-infections are additional risk factors for disease progression and multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) for ICU admission.

Ceftolozane/Tazobactam for Treating Children With Exacerbations of Cystic Fibrosis Due to Pseudomonas aeruginosa: A Review of Available Data.

Ceftolozane-tazobactam is a novel fifth-generation cephalosporin/ß-lactamase inhibitor combination recently approved for treatment of both complicated intra-abdominal and urinary tract infections in adults. Considering its potent bactericidal activity against Pseudomonas aeruginosa, it might represent an important option also for treating children with exacerbations of cystic fibrosis due to Pseudomonas aeruginosa when other alternative treatments have been exhausted. We hereby review available data on the use of ceftolozane-tazobactam in children, focusing on cystic fibrosis.