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1.
Eur J Pediatr ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780652

ABSTRACT

We performed this study to evaluate factors associated with antibiotic prescriptions in children with adenovirus infection, since no studies have attempted to address this aspect in the pediatric population. Retrospective study of children younger than 18 years of age tested positive for adenovirus on a syndromic nasopharyngeal test from 2018 to 2023. We compared the need of pediatric intensive care unit (PICU), invasive ventilation, and other respiratory support, viral etiologies, clinical presentations, imaging, and laboratory results in the precovid (2018-2019) and covid (2020-2022) period. The use of antibiotics was studied with multivariable logistic regression including demographic as well as clinical data as covariates. Two hundred fifty-eight patients were enrolled. One hundred fifty-eight patients received an antibiotic (mean duration 6.2 (±2.7) days (median 4; IQR: 4-7)). Presence of seizures and C-reactive protein values as predictors for antibiotic prescription (OR for seizures: 12.17; 95% CI: 1.42-103.91; p = 0.022; OR for CrP: 1.03; 95% CI: 1.01-1.04; p = 0.001). Seventy-four patients received intravenous antibiotics (74/156, 47.4%). Risk factors for intravenous antibiotic were the presence of decay (OR: 3.74; 95% CI: 1.25-11.71; p = 0.018), CrP values (OR: 1.02; 95% CI: 1.00-1.03; p = 0.001), and presence of seizures (OR: 16.34; 95% CI: 2.65-100.83; p = 0.003). Duration of intravenous antibiotics correlated with the presence of seizures (Coeff: 1.6; 95% CI: 0.41-2.89; p = 0.009) even when adjusted for CrP values.    Conclusion: The clinical presentation of adenovirus infection in children is non-specific, leading to frequent antibiotic prescription despite bacterial co-infections was rare. Higher CrP values and presenting with seizures are significantly associated with a higher risk of receiving antibiotics. Rapid microbiological tests and newer biomarkers can help clinicians to improve antibiotic prescription in this cohort of children. What is Known: • Adenovirus infection is a common cause of fever and respiratory tract infections in children. • Children with adenovirus infections frequently receive antibiotics, but determinants of this practice are poorly established. What is New: • Higher C-reactive protein values and presenting with seizures are significantly associated with antibiotic prescription. • Since the beginning of COVID-19 and implementation of rapid diagnostics, less children with adenovirus infection received antibiotics.

2.
Pediatr Infect Dis J ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38713816

ABSTRACT

BACKGROUND: Cardiopulmonary exercise testing (CPET) is a noninvasive and nonexpensive diagnostic tool, that provides a comprehensive evaluation of the pulmonary, cardiovascular, and skeletal muscle systems' integrated reactions to exercise. CPET has been extensively used in adults with Long COVID (LC), while the evidence about its role in children with this condition is scarce. METHODS: Prospective, case-controlled observational study. Children with LC and a control group of healthy children underwent CPET. CPET findings were compared within the 2 groups, and within the LC groups according to main clusters of persisting symptoms. RESULTS: Sixty-one children with LC and 29 healthy controls were included. Overall, 90.2% of LC patients (55 of 61) had a pathologic test vs 10.3% (3/29) of the healthy control. Children with LC presented a statistically significant higher probability of having abnormal values of peak VO2 (P = 0.001), AT% pred (P <0.001), VO2/HR % (P = 0.03), VO2 work slope (P = 0.002), VE/VCO2 slope (P = 0.01). The mean VO2 peak was 30.17 (±6.85) in LC and 34.37 (±6.55) in healthy patients (P = 0.007). CONCLUSIONS: Compared with healthy controls, children with LC have objective impaired functional capacity (expressed by a low VO2 peak), signs of deconditioning and cardiogenic inefficiency when assessed with CPET. As such, CPET should be routinely used in clinical practice to objectify and phenotype the functional limitations of children with LC, and to follow-up them.

3.
Children (Basel) ; 11(2)2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38397338

ABSTRACT

Introduction: Fever is among the most common reason for medical assessment and antibiotic prescription in practice. The aim of this study was to evaluate positive and negative predictive values of rapid nasopharyngeal swabs for respiratory pathogens to discriminate viral from bacterial infections. Methods: We prospectively tested children with signs and/or symptoms of infections (e.g., fever, cough, wheezing, suspected urinary tract infection) admitted to a paediatric department. Following discharge, clinical phenotypes were assigned defining a cohort of children having probable/certain viral infection, probable/certain bacterial infection, other inflammatory conditions or healthy controls. Results: In this study, 190 children were enrolled (50.5% females, median age 30.5 (8-86) months). In total, 102 patients (53.7%) were affected by respiratory viral infections, 16 (8.4%) by bacterial infections, 29 (15.3%) were healthy controls and 43 (22.6%) were affected by another pathological condition manifested with fever. In total, 84.3% of patients classified as viral infection tested positive for viruses, compared with 18.8% of patients with bacterial infection (p < 0.001), 18.6% of patients with other condition (p < 0.001) and 17.2% of control patients (p < 0.001). The positive predictive value of NPSs in the diagnosis of viral infection was 88.6% and the negative predictive value was 75.0%. Conclusion: Our findings suggest that rapid NPS tests for respiratory viruses are a useful tool to confirm viral infections in children with fever and improve antibiotic use.

4.
Heliyon ; 9(9): e19206, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37662770

ABSTRACT

INTRODUCTION: We performed a single-center, prospective, observational study of newborns born from mothers with microbiologically confirmed SARS-CoV-2 infection in pregnancy or at time of delivery to evaluate acute and mid-term multidisciplinary outcomes. METHODS: Infants were offered a multidisciplinary follow-up consisting of nasopharyngeal Polymerase Chain Reaction test at birth and at 48-72 h of life, auxological and ophthalmological assessments, and serologic testing. RESULTS: 791 women and their 791 children (52.3% males) were included. Most placentas (94.9%) had abnormal inflammatory findings. 171 (27.3%) and 36 (13.7%) children respectively had pathological TEOAEs in at least one ear and bilaterally, while only four of the 85 children that underwent ABR had pathological findings (4.7%). 64 children underwent fluorescein angiography, which resulted pathological only in 1 case (1.6%). Anti-SARS-CoV-2 IgGs were found in up to 60% of children tested at six months of age. Our findings showed no association between the maternal vaccination status or the presence of maternal symptoms during pregnancy and neonatal outcomes. CONCLUSIONS: Our study shows that the large majority of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life have optimal outcomes. Our previous report of abnormal ophthalmologic findings was not confirmed on a larger cohort, while further studies are needed to better characterize audiological outcomes. Further prospective, case-controlled studies are still needed.

5.
J Antimicrob Chemother ; 78(10): 2505-2514, 2023 10 03.
Article in English | MEDLINE | ID: mdl-37606528

ABSTRACT

OBJECTIVES: To assess the impact of carbapenem resistance on mortality in Klebsiella pneumoniae bloodstream infection (BSI) in the era of novel ß-lactam/ß-lactamase inhibitor combinations. MATERIAL AND METHODS: Retrospective study of patients with K. pneumoniae BSI between January and August 2020 in 16 centres (CARBANEW study within the MULTI-SITA project). RESULTS: Overall, 426 patients were included: 107/426 (25%) had carbapenem-resistant K. pneumoniae (CR-Kp) BSI and 319/426 (75%) had carbapenem-susceptible K. pneumoniae (CS-Kp) BSI. Crude cumulative 30 day mortality was 33.8% and 20.7% in patients with, respectively, CR-Kp BSI and CS-Kp BSI (P = 0.027). Carbapenemase production or carbapenemase-encoding genes were detected in 84/98 tested CR-Kp isolates (85.7%), mainly KPC (78/84; 92.9%). Ceftazidime/avibactam was the most frequently used appropriate therapy for CR-Kp BSI (80/107; 74.7%). In multivariable analyses, variables showing an unfavourable association with mortality after correction for multiple testing were age-adjusted Charlson comorbidity index (HR 1.20; 95% CI 1.10-1.31, P < 0.001) and Pitt score (HR 1.33; 95% CI 1.15-1.55, P < 0.001), but not carbapenem resistance (HR 1.28, 95% CI 0.74-2.22, P = 0.410). In a propensity score-matched analysis, there was no difference in mortality between patients appropriately treated with ceftazidime/avibactam for CR-Kp BSI and patients appropriately treated with other agents (mainly meropenem monotherapy or piperacillin/tazobactam monotherapy) for CS-Kp BSI (HR 1.07; 95% CI 0.50-2.29, P = 0.866). CONCLUSIONS: Our results suggest that the increased mortality in CR-Kp BSI compared with CS-Kp BSI is not (or no longer) dependent on the type of therapy in areas where ceftazidime/avibactam-susceptible KPC-producing isolates are the most prevalent type of CR-Kp.


Subject(s)
Bacteremia , Klebsiella Infections , Sepsis , Humans , Ceftazidime/pharmacology , Klebsiella pneumoniae , Klebsiella Infections/drug therapy , Klebsiella Infections/epidemiology , Retrospective Studies , Bacteremia/drug therapy , Azabicyclo Compounds/therapeutic use , Azabicyclo Compounds/pharmacology , beta-Lactamases/genetics , Bacterial Proteins/genetics , Sepsis/drug therapy , Carbapenems/pharmacology , Carbapenems/therapeutic use , beta-Lactamase Inhibitors/therapeutic use , Drug Combinations , Disease Susceptibility , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use
6.
Am J Transplant ; 23(7): 1022-1034, 2023 07.
Article in English | MEDLINE | ID: mdl-37028515

ABSTRACT

We aimed to compare the efficacy of ceftazidime-avibactam (CAZ-AVI) versus the best available therapy (BAT) in solid organ transplant (SOT) recipients with bloodstream infection caused by carbapenemase-producing Klebsiella pneumoniae (CPKP-BSI). A retrospective (2016-2021) observational cohort study was performed in 14 INCREMENT-SOT centers (ClinicalTrials.gov identifier: NCT02852902; Impact of Specific Antimicrobials and MIC Values on the Outcome of Bloodstream Infections Due to ESBL- or Carbapenemase-producing Enterobacterales in Solid Organ Transplantation: an Observational Multinational Study). Outcomes were 14-day and 30-day clinical success (complete resolution of attributable manifestations, adequate source control, and negative follow-up blood cultures) and 30-day all-cause mortality. Multivariable logistic and Cox regression analyses adjusted for the propensity score to receive CAZ-AVI were constructed. Among 210 SOT recipients with CPKP-BSI, 149 received active primary therapy with CAZ-AVI (66/149) or BAT (83/149). Patients treated with CAZ-AVI had higher 14-day (80.7% vs 60.6%, P = .011) and 30-day (83.1% vs 60.6%, P = .004) clinical success and lower 30-day mortality (13.25% vs 27.3%, P = .053) than those receiving BAT. In the adjusted analysis, CAZ-AVI increased the probability of 14-day (adjusted odds ratio [aOR], 2.65; 95% confidence interval [CI], 1.03-6.84; P = .044) and 30-day clinical success (aOR, 3.14; 95% CI, 1.17-8.40; P = .023). In contrast, CAZ-AVI therapy was not independently associated with 30-day mortality. In the CAZ-AVI group, combination therapy was not associated with better outcomes. In conclusion, CAZ-AVI may be considered a first-line treatment in SOT recipients with CPKP-BSI.


Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Klebsiella Infections , Sepsis , Humans , Anti-Bacterial Agents/therapeutic use , Klebsiella pneumoniae , Retrospective Studies , Drug Combinations , Microbial Sensitivity Tests , Klebsiella Infections/drug therapy
7.
Children (Basel) ; 11(1)2023 Dec 30.
Article in English | MEDLINE | ID: mdl-38255368

ABSTRACT

We aimed to investigate if children with their first UTI and a concomitant positive blood culture have a higher risk of abnormalities. We performed a retrospective study of children younger than 18 years of age with their first UTI. Multivariate logistic regression and receiver operating characteristic (ROC) curves were used to evaluate if positive blood cultures are associated with urinary abnormalities. After the screening process, we considered the enrolled 161 children with UTIs. The median age was three months, and 83 were females (43.2%). In multivariate analysis, age (p = 0.001, 95% CI 1.005-1.020), the presence of Pseudomonas aeruginosa or unusual germs in urine cultures (p = 0.002, 95% CI 2.18-30.36) and the positivity of blood cultures (p = 0.001, 95% CI 2.23-18.98) were significantly associated with urinary abnormalities. A model based on these parameters has an AUC of 0.7168 to predict urinary malformations (p = 0.0315). Conclusions include how greater age, a positive blood culture and the presence of Pseudomonas aeruginosa or unusual germs in urine culture in children hospitalised for their first episode of a UTI are factors associated with a significantly higher risk of urinary abnormalities. These data can guide the implementation of more personalized strategies to screen for urinary abnormalities that may be included in future guidelines.

8.
Antibiotics (Basel) ; 11(5)2022 Apr 26.
Article in English | MEDLINE | ID: mdl-35625223

ABSTRACT

P. aeruginosa is still one of the most threatening pathogens responsible for serious hospital-acquired infections. It is intrinsically resistant to many antimicrobial agents and additional acquired resistance further complicates the management of such infections. High rates of combined antimicrobial resistance persist in many countries, especially in the eastern and south-eastern parts of Europe. The aim of this narrative review is to provide a comprehensive assessment of the epidemiology, latest data, and clinical evidence on the current and new available drugs active against P. aeruginosa isolates with limited treatment options. The latest evidence and recommendations supporting the use of ceftolozane-tazobactam and ceftazidime-avibactam, characterized by targeted clinical activity against a significant proportion of P. aeruginosa strains with limited treatment options, are described based on a review of the latest microbiological and clinical studies. Cefiderocol, with excellent in vitro activity against P. aeruginosa isolates, good stability to all ß-lactamases and against porin and efflux pumps mutations, is also examined. New carbapenem combinations are explored, reviewing the latest experimental and initial clinical evidence. One section is devoted to a review of new anti-pseudomonal antibiotics in the pipeline, such as cefepime-taniborbactam and cefepime-zidebactam. Finally, other "old" antimicrobials, mainly fosfomycin, that can be used as combination strategies, are described.

9.
J Fungi (Basel) ; 8(4)2022 Apr 17.
Article in English | MEDLINE | ID: mdl-35448646

ABSTRACT

Patients with coronavirus disease 19 (COVID-19) admitted to the intensive care unit (ICU) often develop respiratory fungal infections. The most frequent diseases are the COVID-19 associated pulmonary aspergillosis (CAPA), COVID-19 associated pulmonary mucormycosis (CAPM) and the Pneumocystis jirovecii pneumonia (PCP), the latter mostly found in patients with both COVID-19 and underlying HIV infection. Furthermore, co-infections due to less common mold pathogens have been also described. Respiratory fungal infections in critically ill patients are promoted by multiple risk factors, including epithelial damage caused by COVID-19 infection, mechanical ventilation and immunosuppression, mainly induced by corticosteroids and immunomodulators. In COVID-19 patients, a correct discrimination between fungal colonization and infection is challenging, further hampered by sampling difficulties and by the low reliability of diagnostic approaches, frequently needing an integration of clinical, radiological and microbiological features. Several antifungal drugs are currently available, but the development of new molecules with reduced toxicity, less drug-interactions and potentially active on difficult to treat strains, is highly warranted. Finally, the role of prophylaxis in certain COVID-19 populations is still controversial and must be further investigated.

10.
Front Pediatr ; 10: 774281, 2022.
Article in English | MEDLINE | ID: mdl-35425724

ABSTRACT

Background: There is increasing evidence that the COVID-19 pandemic disrupted childhood immunization services. However, detailed reports on immunizations and preventive antimalarial prophylactic treatments delivered and how the trends changed in referral centers in low-income countries are still missing. Methods: We performed a retrospective cross-sectional study. Data for vaccinations administered to children <5 years of age, according to the local vaccination schedule, were extracted from the official records of the Kent Community Health Post, Sierra Leone, in the period between April 2019 and March 2021. We compared the vaccinations performed in the first year, considered as a pre-Covid period, with the second year, post-Covid period. Both the period was then divided in four trimester each and the same analysis was operated for each trimester. A Chi-square goodness of fit test was performed to compare the number of vaccinations performed both in the 2 years and in the 8 trimesters. Findings: Seven thousand two hundred and eighty-three vaccinations were administered: 4,641 in the period between April 2019 and March 2020 and 2,642 between April 2020 and March 2021. The drop in immunizations performed began as soon as the first cases were described in China. The drops were statistically significant when the first three trimesters of the two study periods were compared, while no statistically significant differences were observed for all the vaccines performed in the 4th trimesters. Vaccines administered at birth (BCG) were less affected compared to booster vaccinations. Conclusions: Immunizations administered in a referral health center in Sierra Leone significantly declined during the pandemic. Although the decline was less pronounced in the last months of the pandemic, we don't think that the small increase would indicate the recovery of previously missed vaccinations. These findings open new public health challenges for the coming years.

11.
JAC Antimicrob Resist ; 4(1): dlac022, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35265842

ABSTRACT

Objectives: To explore the real-life performance of meropenem/vaborbactam for treating serious KPC-producing Klebsiella pneumoniae infections, including those resistant to ceftazidime/avibactam. Methods: A retrospective observational cohort study was conducted in 12 Italian hospitals. Enrolled patients had K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) infections (59.5% of which were ceftazidime/avibactam resistant). Patients who received ≥72 h of meropenem/vaborbactam therapy (with or without other antimicrobials) in a compassionate-use setting were included. Results: The 37 infections (all hospital-acquired) were mainly bacteraemic (BSIs, n = 23) or lower respiratory tract infections (LRTIs, n = 10). Clinical cure was achieved in 28 (75.6%) cases and microbiologically confirmed in all 25 with follow-up cultures. Three (10.7%) of the 28 clinical cures (all BSIs, 2/3 microbiologically confirmed) were followed by in-hospital recurrences after meropenem/vaborbactam was discontinued (median interval: 18 days). All three recurrences were susceptible to meropenem/vaborbactam and successfully managed with meropenem/vaborbactam combined with colistin or fosfomycin. Nine patients (24.3%) (all with BSIs or LRTIs) died in hospital with persistent signs of infection. Most were aged over 60 years, with high comorbidity burdens and INCREMENT scores ≥8. Only one had received meropenem/vaborbactam monotherapy. Six began meropenem/vaborbactam therapy >48 h after infection onset. Outcomes were unrelated to the isolate's ceftazidime/avibactam susceptibility status. The single adverse event observed consisted of severe leukopenia with thrombocytopenia. Conclusions: With the well-known limitations of real-life retrospective studies, our results support previous findings indicating that meropenem/vaborbactam therapy will be a safe, effective tool for managing serious KPC-Kp infections, including the increasing proportion displaying resistance to ceftazidime/avibactam.

12.
Antibiotics (Basel) ; 11(2)2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35203796

ABSTRACT

BACKGROUND: Pseudomonas aeruginosa represents, among the nosocomial pathogens, one of the most serious threats, both for the severity of its clinical manifestations and its ability to develop complex profiles of resistance; Methods: we retrospectively collected the data of 21 patients admitted to a tertiary-care University Hospital of Rome with infections due to XDR-P. aeruginosa isolates during the second half of 2020; Results: in our institution, the percentage of XDR-P. aeruginosa isolates is 3.1%. None of the patients was admitted to the intensive care unit at the moment of the infection's onset. Susceptibility to colistin was preserved in all the tested isolates. Rates of resistance to ceftolozane/tazobactam and ceftazidime/avibactam in these XDR strains were consistent; Conclusions: XDR-P. aeruginosa can be a threatening problem even outside the ICUs, especially in frail patients in wards with features of long-term acute care hospitals. In such a setting, ceftolozane/tazobactam and ceftazidime/avibactam should be administered with caution taking into account the microbiological susceptibility results. Colistin, even with its known safety and efficacy limits, could represent the only available therapeutic option due to its highly preserved susceptibility against XDR isolates of P. aeruginosa.

13.
Antibiotics (Basel) ; 10(12)2021 Dec 19.
Article in English | MEDLINE | ID: mdl-34943767

ABSTRACT

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.

14.
Clin Infect Dis ; 73(9): 1664-1676, 2021 11 02.
Article in English | MEDLINE | ID: mdl-33618353

ABSTRACT

BACKGROUND: A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. METHODS: We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. RESULTS: The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P = .79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock (P = .002), neutropenia (P < .001), or an INCREMENT score ≥8 (P = .01); with lower respiratory tract infection (LRTI) (P = .04); and with CAZ-AVI dose adjustment for renal function (P = .01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P = .006). All associations remained significant after propensity score adjustment. CONCLUSIONS: CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug's seemingly more limited efficacy in LRTIs and potential survival benefits of prolonging CAZ-AVI infusions to ≥3 hours.


Subject(s)
Klebsiella Infections , Klebsiella pneumoniae , Adult , Anti-Bacterial Agents/therapeutic use , Azabicyclo Compounds/therapeutic use , Bacterial Proteins , Ceftazidime/therapeutic use , Drug Combinations , Humans , Klebsiella Infections/drug therapy , Microbial Sensitivity Tests , Retrospective Studies , beta-Lactamases
15.
Sci Rep ; 10(1): 20203, 2020 11 19.
Article in English | MEDLINE | ID: mdl-33214601

ABSTRACT

Brown adipose tissue (BAT) thermogenesis is considered a potential target for treatment of obesity and diabetes. In vitro data suggest dopamine receptor signaling as a promising approach; however, the biological relevance of dopamine receptors in the direct activation of BAT thermogenesis in vivo remains unclear. We investigated BAT thermogenesis in vivo in mice using peripheral administration of D1-agonist SKF38393 or D2-agonist Sumanirole, infrared thermography, and in-depth molecular analyses of potential target tissues; and ex vivo in BAT explants to identify direct effects on key thermogenic markers. Acute in vivo treatment with the D1- or D2-agonist caused a short spike or brief decrease in BAT temperature, respectively. However, repeated daily administration did not induce lasting effects on BAT thermogenesis. Likewise, neither agonist directly affected Ucp1 or Dio2 mRNA expression in BAT explants. Taken together, the investigated agonists do not seem to exert lasting and physiologically relevant effects on BAT thermogenesis after peripheral administration, demonstrating that D1- and D2-receptors in iBAT are unlikely to constitute targets for obesity treatment via BAT activation.


Subject(s)
Adipose Tissue, Brown/drug effects , Dopamine Agonists/pharmacology , Receptors, Dopamine D1/agonists , Receptors, Dopamine D2/agonists , Thermogenesis/drug effects , 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology , Adipose Tissue, Brown/metabolism , Animals , Benzimidazoles/pharmacology , Male , Mice , Signal Transduction/drug effects , Thermography
16.
Open Forum Infect Dis ; 7(8): ofaa233, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32766378

ABSTRACT

BACKGROUND: Candida species are among the most frequent causative agents of health care-associated bloodstream infections, with mortality >40% in critically ill patients. Specific populations of critically ill patients may present peculiar risk factors related to their reason for intensive care unit admission. The primary objective of the present study was to assess the predictors of candidemia after open heart surgery. METHODS: This retrospective, matched case-control study was conducted in 8 Italian hospitals from 2009 to 2016. The primary study objective was to assess factors associated with the development of candidemia after open heart surgery. RESULTS: Overall, 222 patients (74 cases and 148 controls) were included in the study. Candidemia developed at a median time (interquartile range) of 23 (14-36) days after surgery. In multivariable analysis, independent predictors of candidemia were New York Heart Association class III or IV (odds ratio [OR], 23.81; 95% CI, 5.73-98.95; P < .001), previous therapy with carbapenems (OR, 8.87; 95% CI, 2.57-30.67; P = .001), and previous therapy with fluoroquinolones (OR, 5.73; 95% CI, 1.61-20.41; P = .007). Crude 30-day mortality of candidemia was 53% (39/74). Septic shock was independently associated with mortality in the multivariable model (OR, 5.64; 95% CI, 1.91-16.63; P = .002). No association between prolonged cardiopulmonary bypass time and candidemia was observed in this study. CONCLUSIONS: Previous broad-spectrum antibiotic therapy and high NYHA class were independent predictors of candidemia in cardiac surgery patients with prolonged postoperative intensive care unit stay.

17.
Int J Infect Dis ; 97: 23-26, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32497794

ABSTRACT

Economical and psychological consequences of the lockdown in low-resource setting in rural Africa are unknown. We drafted a survey in order to address the social impact of COVID-19 lockdown on a rural village in Sierra Leone. The survey developed by the study group and translated in the local language, distributed to the householders of the village on April 13th and responses collected on April 14th, when Sierra Leone was on day 11 of lockdown. The questions aimed to assess in the community the following items: age group, main activities before lockdown, change in income and ability to feed the family during lockdown, anxiety during lockdown. 78 householders (100% of Bureh Town) replied. All, expect one, declared a 51-80% (19.2%) to 81-100% (79.4%) reduction of weekly income compared with the pre-lockdown period, declaring difficulties in providing food for the family members (82%), and anxiety (60%). Our analyses showed that people lost their jobs and have difficulties in providing food for their families. Highlights: Our analyses in a low resource setting in rural Africa in Sierra Leone, West Africa, showed that people lost their jobs and have difficulties in providing food for their families, as a consequence of COVID-19 lockdown.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Adolescent , Adult , Aged , COVID-19 , Child , Child, Preschool , Coronavirus Infections/economics , Female , Health Resources , Humans , Income , Male , Middle Aged , Pandemics/economics , Pneumonia, Viral/economics , Rural Population , SARS-CoV-2 , Sierra Leone , Young Adult
18.
Int J Antimicrob Agents ; 55(4): 105900, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31931150

ABSTRACT

This study aimed to characterise UTIs caused by Pseudomonas aeruginosa in hospitalised adults and to identify risk factors for infections caused by multidrug-resistant (MDR) strains. A retrospective case-case-control study was conducted in two Italian teaching hospitals. Totally, 242 monomicrobial P. aeruginosa UTIs were analysed; 65 (26.9%) were caused by MDR strains. Clinical treatment failure at 72 h in 215 patients receiving empirical therapy was more frequent in MDR versus non-MDR cases [35/59 (59.3%) vs. 55/156 (35.3%); P = 0.001], particularly when a ß-lactam/ß-lactamase inhibitor or fluoroquinolone was initially prescribed. By Day 7 (when all regimens were consistent with antimicrobial susceptibility results), treatment failure rates were similar [MDR 15/65 (23.1%) vs. non-MDR 25/177 (14.1%); P = 0.09]. In-hospital mortality rates remained low in both groups [6/65 (9.2%) vs. 22/177 (12.4%); P = 0.49], but median hospital stay for MDR cases was longer (48 vs. 22 days; P ≤ 0.001). Models for predicting MDR and non-MDR P. aeruginosa UTIs displayed good discriminatory power. Presence of ≥3 risk factors for MDR P. aeruginosa UTI was associated with an OR for this outcome of 7.44 (95% CI 3.24-17.57; P < 0.001; specificity 91%, accuracy 75%). The model for predicting non-MDR P. aeruginosa UTI displayed similar accuracy (74%) with a risk factor burden threshold of ≥2 (OR = 7.02, 95% CI 4.61-10.70; P < 0.001). Risk factor assessment can identify UTIs in hospitalised patients likely to be caused by MDR P. aeruginosa, thereby facilitating targeted infection control and timelier effective treatment.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Resistance, Multiple, Bacterial/genetics , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/drug effects , Urinary Tract Infections/drug therapy , beta-Lactamase Inhibitors/therapeutic use , Aged , Aged, 80 and over , Case-Control Studies , Cross Infection/drug therapy , Cross Infection/microbiology , Female , Fluoroquinolones/therapeutic use , Hospitalization , Humans , Italy , Male , Middle Aged , Pseudomonas aeruginosa/genetics , Retrospective Studies , Risk Factors , Urinary Tract Infections/microbiology
19.
Front Pediatr ; 8: 587638, 2020.
Article in English | MEDLINE | ID: mdl-33643963

ABSTRACT

Growing evidences are showing the potential indirect effects of the Coronavirus Disease 2019 (COVID-19) on the health systems of low-resource settings, where diseases such as Tuberculosis, Human Immunodeficiency Virus (HIV) and Malaria represent major killers. Therefore, we performed a retrospective study aimed to evaluate the impact of COVID-19 on Malaria programs in a peripheral region of Sierra Leone, previously involved by the Ebola outbreak in 2015, when malaria care have been impaired since local health systems were overwhelmed by Ebola cases. During COVID-19 in Sierra Leone, we did not notice a significant drop in malaria diagnosis in children, suggesting that a proactive approach in the management of malaria in endemic countries during COVID-19 may have had a positive impact. A comprehensive approach that include also educational activities to sensitize the local population, was useful to guarantee successful malaria diagnosis and treatment, and prevents excess of malaria deaths due to potential disruption of the local health systems related to the SARS-CoV-2 pandemic.

20.
J Glob Antimicrob Resist ; 20: 43-49, 2020 03.
Article in English | MEDLINE | ID: mdl-31207379

ABSTRACT

OBJECTIVES: The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB). METHODS: Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed. RESULTS: A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52-73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24-8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69-13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17-0.88; P = 0.024) was associated with use of colistin monotherapy. CONCLUSION: Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Colistin/administration & dosage , Drug Resistance, Multiple, Bacterial , Gram-Negative Bacterial Infections/drug therapy , Respiratory Tract Infections/drug therapy , Sepsis/drug therapy , Administration, Intravenous , Aged , Anti-Bacterial Agents/therapeutic use , Colistin/therapeutic use , Cross-Sectional Studies , Drug Prescriptions/statistics & numerical data , Drug Therapy, Combination/statistics & numerical data , Endemic Diseases , Female , Gram-Negative Bacterial Infections/epidemiology , Humans , Italy/epidemiology , Male , Middle Aged , Respiratory Tract Infections/microbiology , Sepsis/microbiology
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