Severe cellulitis from methicillin-resistant Staphylococcus aureus (MRSA) in a couple of preterm twins: a case report.

BACKGROUND: Preterms are at risk of systemic infections as the barrier function of their immature skin is insufficient. The long period of hospitalization and the huge number of invasive procedures represent a risk factor for complications. Among the nosocomial infections of the skin, methicillin-resistant Staphylococcus aureus (MRSA) is associated with significant morbidity and mortality. We report a clinical case of cellulitis and abscess in two preterm twins caused by MRSA in a tertiary level Neonatal Intensive Care Unit (NICU). CASE PRESENTATION: Two preterm female babies developed cellulitis from MRSA within the first month of extrauterine life. The first one (BW 990 g) showed signs of clinical instability 4 days before the detection of a hyperaemic and painful mass on the thorax. The second one (BW 1240 g) showed signs of clinical instability contextually to the detection of an erythematous, oedematous and painful area in the right submandibular space. In both cases the diagnosis of cellulitis was confirmed by ultrasound. A broad spectrum, multidrug antimicrobial therapy was administered till complete resolution. CONCLUSIONS: Due to the characteristic antibiotic resistance of MRSA and the potential complications of those infections in such delicate patients, basic prevention measures still represent the key to avoid the spreading of neonatal MRSA infections in NICUs, which include hand hygiene and strict precautions, as well as screening of patients for MRSA on admission and during hospital stay, routine prophylactic topical antibiotic of patients, enhanced environmental cleaning, cohorting and isolation of positive patients, barrier precautions, avoidance of ward crowding, and, in some units, surveillance, education and decolonization of healthcare workers and visiting parents.

Clinical and Radiological Features of Pneumocystis jirovecii Pneumonia in Children: A Case Series.

BACKGROUND: Pneumocytis jirovecii pneumonia (PJP) has high mortality rates in immunocompromised children, even though routine prophylaxis has decreased in incidence. The aim of this case series is to present the radiological and clinical pathway of PJP in a pediatric population. DESCRIPTION OF CASES: All PJP cases in non-HIV/AIDS patients diagnosed at Istituto Giannina Gaslini Pediatric Hospital in Genoa (Italy) from January 2012 until October 2022 were retrospectively evaluated. Nine cases were identified (median age: 8.3 years), and of these, 6/9 underwent prophylaxis with trimethoprim/sulfamethoxazole (TMP/SMX; five once-a-week schedules and one three times-a-week schedule), while 3/9 did not receive this. PJP was diagnosed by real-time PCR for P. jirovecii-DNA in respiratory specimens in 7/9 cases and two consecutive positive detections of ß-d-glucan (BDG) in the serum in 2/9 cases. Most patients (6/8) had a CT scan with features suggestive of PJP, while one patient did not undergo a scan. All patients were treated with TMP/SMX after a median time from symptoms onset of 3 days. In 7/9 cases, empirical TMP/SMX treatment was initiated after clinical suspicion and radiological evidence and later confirmed by microbiological data. Clinical improvement with the resolution of respiratory failure and 30-day survival included 100% of the study population. DISCUSSION: Due to the difficulty in obtaining biopsy specimens, PJP diagnosis is usually considered probable in most cases. Moreover, the severity of the clinical presentation often leads physicians to start TMP/SMX treatment empirically. BDG proved to be a useful tool for diagnosis, and CT showed good accuracy in identifying typical patterns. In our center, single-day/week prophylaxis was ineffective in high-risk patients; the three-day/week schedule would, therefore, seem preferable and, in any case, should be started promptly in all patients who have an indication of pneumonia.

Whipple Disease Presenting as Isolated Transverse Myelitis with Permanent Neurological Damage in a Patient with Systemic Lupus Erythematosus: A Case Report of a Difficult Diagnosis with a Literature Review.

We describe an atypical case of Whipple disease exclusively involving the spinal cord in an adolescent receiving immunosuppressive therapy for systemic lupus erythematosus. The diagnosis was particularly difficult since lupus and Whipple disease can present similar clinical features and the patient's prolonged contact with sewage was initially not mentioned. A literature review of the clinical, imaging, diagnostic, and therapeutic challenges of Whipple disease is also performed.

Application of the Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide the empiric antibiotic treatment of febrile neutropenia in oncological paediatric patients: experience from two paediatric hospitals in Northern Italy.

BACKGROUND: Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres. METHODS: We included blood cultures from patients with a bloodstream infection and neutropenia admitted to the Paediatric Haematology-Oncology wards in Padua and Genoa Hospitals from 2016 to 2021. WISCAs were developed by estimating the coverage of 20 antibiotics as monotherapy and of 21 combined regimens with a Bayesian probability distribution. RESULTS: We collected 350 blood cultures, including 196 g-negative and 154 g-positive bacteria. Considering the most used antibiotic combinations, such as piperacillin-tazobactam plus amikacin, the median coverage for the pool of bacteria collected in the study was 78%. When adding a glycopeptide, the median coverage increased to 89%, while the replacement of piperacillin-tazobactam with meropenem did not provide benefits. The developed WISCAs showed that no monotherapy offered an adequate coverage rate for the identified pathogens. CONCLUSIONS: The application of WISCA offers the possibility of maximizing the clinical utility of microbiological surveillance data derived from large hospitals to inform the choice of the best empiric treatment while contributing to spare broad-spectrum antibiotics.

Therapeutic drug monitoring of glycopeptide antimicrobials: An overview of liquid chromatography-tandem mass spectrometry methods.

Therapeutic drug monitoring (TDM) is a critical clinical tool used to optimize the safety and effectiveness of drugs by measuring their concentration in biological fluids. These fluids are primarily plasma or blood. TDM, together with real-time dosage adjustment, contributes highly to the successful management of glycopeptide antimicrobial therapies. Understanding pharmacokinetic/pharmacodynamic (PK/PD) properties is vital for optimizing antimicrobial therapies, as the efficacy of these therapies depends on both the exposure of the patient to the drug (PK) and pharmacodynamic (PD) parameters such as the in vitro estimated minimum drug concentration that inhibits bacterial growth (MIC). Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is widely recognized as the gold standard for measuring small molecules, such as antibiotics. This review provides a comprehensive overview of LC-MS/MS methods available for TDM of glycopeptide antibiotics, including vancomycin, teicoplanin, dalbavancin, oritavancin, and telavancin.

Real-Life Vancomycin Therapeutic Drug Monitoring in Coagulase-Negative Staphylococcal Bacteremia in Neonatal and Pediatric Intensive Care Unit: Are We Underestimating Augmented Renal Clearance?

Bloodstream infections (BSI) from coagulase-negative-staphylococci (CoNS) are among the most frequent healthcare-related infections. Their treatment involves the use of vancomycin, a molecule whose optimal pharmacokinetic/pharmacodynamic (PK/PD) target for efficacy and safety is an area-under-curve/minimum inhibitory concentration (AUC/MIC) ratio ≥ 400 with AUC < 600. BSIs from CoNS in pediatric and neonatal intensive care unit that occurred at the Gaslini Institute over five years were evaluated to investigate the efficacy of vancomycin therapy in terms of achieving the desired PK/PD target and determining whether any variables interfere with the achievement of this target. AUC/MIC ≥ 400 with AUC < 600 at 48 and 72 h after therapy initiation was achieved in only 21% of the neonatal population and 25% of the pediatric population. In the pediatric population, an inverse correlation emerged between estimated glomerular filtration rate (eGFR) and achieved AUC levels. Median eGFR at 72 h was significantly higher (expression of hyperfiltration) in events with AUC < 400, compared with those with AUC ≥ 400 (p < 0.001). A cut-off value of eGFR in the first 72 h has been identified (145 mL/min/1.73 m2), beyond which it is extremely unlikely to achieve an AUC ≥ 400, and therefore a higher dose or a different antibiotic should be chosen.

Clostridioides difficile infection in the allogeneic hematopoietic cell transplant recipient.

Clostridioides difficile (CD) is one of the most important causes of diarrhea in hospitalized patients, in particular those who undergo an allogeneic hematopoietic cell transplant (allo-HCT) and who are more at risk of developing a CD infection (CDI) due to frequent hospitalizations, iatrogenic immunosuppression, and prolonged antibiotic cycles. CDI may represent a severe condition in allo-HCT patients, increasing the length of hospitalization, influencing the intestinal microbiome with a bidirectional association with graft-versus-host disease, and leading to unfavorable outcomes, including death. The diagnosis of CDI requires the exclusion of other probable causes of diarrhea in HCT patients and is based on highly sensitive and highly specific tests to distinguish colonization from infection. In adult patients, fidaxomicin is recommended as first-line, with oral vancomycin as an alternative agent. Bezlotoxumab may be used to reduce the risk of recurrence. In pediatric patients, vancomycin and metronidazole are still suggested as first-line therapy, but fidaxomicin will probably become standard in pediatrics in the near future. Because of insufficient safety data, fecal microbiota transplantation is not routinely recommended in HCT in spite of promising results for the management of recurrences in other populations.

Clinical and Microbiological Characteristics of Deep Neck Abscesses in Pediatrics: Analysis of a Case Series from a 3rd Level Pediatric Hospital.

As there is currently no consensus on managing deep neck infections in pediatric populations, we report a case series from a large pediatric hospital. Clinical data of patients discharged from Istituto Gaslini-Children's Hospital from January 2014 to June 2020 with peritonsillar, parapharyngeal, or retropharyngeal abscess diagnoses were collected. A total of 59 patients were identified. Patients underwent surgical drainage in 47% of cases. Streptococcus mitis/oralis was the most isolated pathogen. Surgically treated patients did have larger abscesses compared to others, but there were no differences in the duration of hospitalization. Children who received NSAIDs at home had significant delays in diagnosis (median 4 vs. 1.5 days, p = 0.008). In our experience, clinical presentation of DNIs is often evocative, but evaluation should include imaging with CT/MRI. Surgery is effective in larger abscesses, allowing for etiological diagnosis with consequent antibiotic adjusting. From an anamnestic point of view, home medications such as NSAIDs could delay diagnosis.

Pediatric SARS-CoV-2-Related Diplopia and Mesencephalic Abnormalities.

Objective: This case report describes a patient with mesencephalic MRI signal abnormality and diplopia, possibly associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods: We describe a boy with binocular diplopia and nystagmus. The pattern of serology positivity and negative direct research of SARS-CoV-2 RNA in our patient allowed us to consider novel coronavirus as the trigger of possible immune-mediated phenomena against the central nervous system. Results: During hospitalization, blood tests revealed a recent SARS-CoV-2 infection. MRI revealed hyperintensity of the mesencephalic tegmentum and periaqueductal region, consistent with an inflammatory lesion of the midbrain tegmentum. Viral and bacterial molecular screening on cerebrospinal fluid and isoelectrofocusing analysis, anti-myelin oligodendrocyte glycoprotein, anti-aquaporine-4, and anti-N-methyl-d-aspartate antibodies were negative. The patient was treated with steroids and immunoglobulin therapy with complete remission of neurologic symptoms. Discussion: This report expands the spectrum of pediatric COVID-19-associated neurologic symptoms and highlights a possible isolated neurologic COVID-19-related symptom.

Epidemiology of Antibiotic Resistant Pathogens in Pediatric Urinary Tract Infections as a Tool to Develop a Prediction Model for Early Detection of Drug-Specific Resistance.

Antibiotic resistance is an increasing problem, especially in children with urinary tract infections. Rates of drug-specific resistant pathogens were reported, and an easy prediction model to guide the clinical decision-making process for antibiotic treatment was proposed. Data on microbiological isolation from urinoculture, between January 2007−December 2018 at Istituto Gaslini, Italy, in patients aged <19 years were extracted. Logistic regression-based prediction scores were calculated. Discrimination was determined by the area under the receiver operating characteristic curve; calibration was assessed by the Hosmer and Lemeshow test and the Spiegelhalterz test. A total of 9449 bacterial strains were isolated in 6207 patients; 27.2% were <6 months old at the first episode. Enterobacteriales (Escherichia coli and other Enterobacteriales) accounted for 80.4% of all isolates. Amoxicillin-clavulanate (AMC) and cefixime (CFI) Enterobacteriales resistance was 32.8% and 13.7%, respectively, and remained quite stable among the different age groups. On the contrary, resistance to ciprofloxacin (CIP) (overall 9.6%) and cotrimoxazole (SXT) (overall 28%) increased with age. After multivariable analysis, resistance to AMC/CFI could be predicted by the following: sex; age at sampling; department of admission; previous number of bacterial pathogens isolated. Resistance to CIP/SXT could be predicted by the same factors, excluding sex. The models achieved very good calibration but moderate discrimination performance. Specific antibiotic resistance among Enterobacteriales could be predicted using the proposed scoring system to guide empirical antibiotic choice. Further studies are needed to validate this tool.

Early and Late Onset Neonatal Sepsis: Epidemiology and Effectiveness of Empirical Antibacterial Therapy in a III Level Neonatal Intensive Care Unit.

Bloodstream infections play an important role in neonatal morbidity and mortality. In this study, we retrospectively analyzed etiology and antibiotic resistance profiles of bacteria isolated from blood or Cerebro Spinal Fluid (CSF) cultures to evaluate the appropriateness of initial empirical therapy of neonatal sepsis. METHODS: microbiological data from patients admitted to Neonatal Intensive Care Unit (NICU), from January 2005 to October 2018, were anonymously extracted from the Laboratory of Microbiology database. According to the neonatal sepsis definition for patients admitted to NICU, positive cultures obtained within the first 72 h of life were labeled as Early Onset Sepsis (EOS); and Late Onset Sepsis (LOS) for those obtained later. RESULTS: 859 bacterial strains, 846 from blood and 13 from CSF, were detected in 611 neonates. In EOS, 75 blood cultures were found: 61 yielded Gram-positives and 14 Gram-negatives. Coagulase Negative Staphylococci (CoNS) represented the majority (52% n = 39). Streptococcus agalactiae and Escherichia coli were both isolated in 8% (n = 6) of cases. 784 strains were isolated in LOS: 686 (87%) Gram-positives and 98 (13%) Gram-negatives. CoNS represented most pathogens (n = 560, 71.4%) followed by Staphylococcus aureus (n = 57, 7.3%) and Enterococcus faecalis (n = 33, 4.2%). Ampicillin/gentamicin therapy resulted effective in 15/20 (75%) of EOS isolates. Internal protocol for LOS initial empirical therapy, calling for piperacillin/tazobactam and vancomycin resulted effective in 98.5% (734/745) of LOS strains. CONCLUSIONS: knowledge of local epidemiology of resistant pathogens, both in EOS and LOS, is fundamental to set up an effective empirical therapy in NICU. Aminoglycosides were fundamental in EOS. On the other side, LOS empirical therapy with vancomycin is sustained by the observation of 38% of methicillin resistance among S. aureus and about 95% in CoNS.

Factors Associated with Inadequate Intravenous Colistin Dosages: Post Hoc Analysis of a Multicenter, Cross-Sectional Study.

Colistin is a last-resort agent for the treatment of infections due to Gram-negative bacteria with difficult-to-treat resistance. The primary objective of this post hoc analysis of a cross-sectional study conducted in 22 Italian hospitals was to assess factors associated with inadequate intravenous colistin dosage. Overall, 187 patients receiving intravenous colistin were included in the analyses. Inadequate colistin dosages were administered in 27% of cases (50/187). In multivariable analysis, AKI (dummy variable with KDIGO stage 0 as a reference, odds ratio (OR) 3.98 with 95% confidence interval (CI) 1.48-10.74 for stage 1, OR 4.44 with 95% CI 1.17-16.93 for stage 2, OR 9.41 with 95% CI 1.59-55.70 for stage 3; overall p = 0.001) retained an independent association with inadequate colistin dosage, whereas the presence of a central venous catheter was associated with adequate colistin dosage (OR: 0.34 for inadequate dosage, 95% CI: 0.16-0.72, p = 0.004). These results were confirmed in an additional multivariable model with the center as a random effect. The association between AKI and inadequate dosage may reflect the perception of an increased risk of nephrotoxicity in patients with impaired renal function, which nonetheless should not be accompanied by dosage reductions beyond those recommended and could represent the target of dedicated antimicrobial stewardship efforts.

Contact tracing, use of surgical masks, hand hygiene and social distancing represent a bundle of effective measures to control SARS-CoV-2 spreading among healthcare workers in a paediatric hospital.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent of pandemic coronavirus disease 2019 (COVID 19) Protection from virus exposure in children's hospital is a pivotal aspect of SARS-COV-2 pandemic control. Healthcare workers (HCW) could play an important role in viral infection in-hospital spread. Infection control measures were thus implemented to protect fragile patients and healthcare workers.We retrospectively described a HCW infectionscase-series due to SARS-CoV-2 from February 24th to July 31stat the IRCCS Istituto Giannina Gaslini. Seven separate cases of SARS-CoV-2 infection were observed among healthcare workers, with a total of 395 contacts, and 23 (6%) secondary case. A program of contact tracing and quarantine of SARS-CoV-2 positive HCW, screening of asymptomatic HCW, use of surgical masks, hand hygiene, social distancing and use of PPE in COVID-19 cases assistance prevented the spread of the virus to patients and blocked the diffusion within the hospital.

Impact of rotavirus vaccine in reducing hospitalization rates in pediatric patients: a single center experience in Italy.

Rotavirus is a major cause of acute gastroenteritis in children under 5 years of age, with severe illness occurring in 30-40% of cases. In Italian region of Liguria, vaccination with a two-dose human attenuated vaccine was introduced in 2013. We conducted a retrospective study to assess the impact of rotavirus vaccine on hospitalizations for rotavirus-related gastroenteritis (RVGE) at the IRCCS Istituto Giannina Gaslini. Every hospitalization due to laboratory-confirmed RVGE and acute gastroenteritis of unknown origin (AGUO) in patients aged 0-14 years in the period 2008-2019 were anonymously extracted. Vaccine coverage were obtained from the regional vaccination registry. The results were divided in 2008-2012 (before RV vaccine) and 2013-2019 (after) periods. From 2008 to 2012, there was a continuous reduction of AGUO hospitalizations while RVGE increased. Since 2013, a reduction in hospitalization rate was observed for RVGE with a sharp decrease from 17.81 per 10.000 children in 2012 to 0.79 per 10,000 in 2019, parallel with the ascending values of RV vaccination coverage that increased from 36.3% in 2013 to 63.9% in 2019. A significant negative correlation was found between the proportions of vaccinated newborns and RVGE rates (p = .012). Intussusception-related hospitalization did not show substantial modifications. We confirm vaccination as a safe practice that has a significant impact in pediatric hospitalization rates.

First Case of Candida auris Colonization in a Preterm, Extremely Low-Birth-Weight Newborn after Vaginal Delivery.

Candida auris is a multidrug-resistant, difficult-to-eradicate pathogen that can colonize patients and health-care environments and cause severe infections and nosocomial outbreaks, especially in intensive care units. We observed an extremely low-birth-weight (800 g), preterm neonate born from vaginal delivery from a C. auris colonized mother, who was colonized by C. auris within a few hours after birth. We could not discriminate whether the colonization route was the birth canal or the intensive care unit environment. The infant died on her third day of life because of complications related to prematurity, without signs or symptoms of infections. In contexts with high rates of C.auris colonization, antifungal prophylaxis in low-birth-weight, preterm neonates with micafungin should be considered over fluconazole due to the C. auris resistance profile, at least until its presence is excluded.

Antibiotic susceptibility of Staphylococcus aureus isolated from skin lesions in children. A retrospective analysis from a tertiary care Italian pediatric hospital.

Antibiotic susceptibility of S. aureus was retrospectively assessed in 1833 strains isolated from skin lesions observed in an Italian tertiary care hospital. Methicillin resistance was more frequent in outpatients than in inpatients (18% vs. 14%, p = 0.04) as well as resistance to cotrimoxazole (8% vs. 4.1%, p < 0.001). Resistance to ampicillin was 99% in both groups, while for clindamycin it was 11% and 14%, respectively. Among topical antibiotics fusidic acid showed the better resistance profile (3%). Antibiotic resistance in pediatric skin infection in outpatients could represent a therapeutic problem in Italy.

Resistance to Antibiotics of Uropathogen Bacteria Isolated From Urine and Blood in Pediatric Cancer Patients: A Single Center, 12-year Study.

Resistant pathogens have become a major healthcare problem in children with cancer, causing different kinds of infections such as the bloodstream ones, most common, and most frequently described and the urinary tract ones, of which less data are available. We analyzed and compared the proportions, and the trends of resistance in pathogens isolated from blood and urines in children with cancer followed in IRCCS Istituto Giannina Gaslini, Genova, Italy, from January 2007 to December 2018. Overall, 345 strains detected in urines and 282 in bloodstream infections were analyzed. Enterobacteriales were the most frequently isolated pathogens. During the study period in urines, there was a significant increase of resistance to ceftazidime, ciprofloxacin, piperacillin/tazobactam, and trimethoprim-sulfamethoxazole, but pathogens from blood were significantly more frequently resistant to amikacin, piperacillin/tazobactam, and combination therapy piperacillin/tazobactam+amikacin, even if with a decreasing trend during the study period. These data confirm the importance of surveillance of isolated microorganism and antibiotic resistance in cancer children.

Intravenous isavuconazole can be administered 5 days-a-week. A possibility suggested by a real-life observation.

In this report it is shown that intravenous formulation of isavuconazole could be administered 5/7 days a week in patients who can not swallow capsules, once the steady state has been stably reached and maintained, thanks to its very long half-life. In this case TDM should be highly recommended.