Pharmacodynamic and immunological interactions of amphotericin B formulations and voriconazole with human neutrophils against mature Scedosporium apiospermum and Fusarium spp. biofilms.

BACKGROUND: Mould infections caused by Scedosporium apiospermum and Fusarium solani species complex (FSSC) biofilms are rising among immunocompromised and immunocompetent patients. Little is known about the immunomodulatory effects of antifungal agents against these moulds. We examined the effects of deoxycholate and liposomal amphotericin B (DAmB, LAmB) and voriconazole on antifungal activities and immune responses of neutrophils (PMNs) against mature biofilms compared with their planktonic counterparts. METHODS: Antifungal activity of human PMNs exposed to mature biofilms and planktonic cells for 24 h was determined at effector-to-target ratios of 2:1 and 5:1, alone or combined with DAmB, LAmB and voriconazole, assessed as fungal damage by XTT assay. Cytokine production was evaluated by multiplex ELISA, following PMN stimulation with biofilms in the presence/absence of each drug. RESULTS: All drugs showed additive or synergistic effects with PMNs against S. apiospermum at 0.03-32 mg/L. They showed antagonism primarily against FSSC at 0.06-64 mg/L. Increased IL-8 was produced by PMNs exposed to S. apiospermum biofilms plus DAmB or voriconazole compared with PMNs exposed to biofilms alone (P < 0.01). During combined exposure, IL-1ß was increased, an effect only counteracted by increased levels of IL-10 caused by DAmB (P < 0.01). LAmB and voriconazole caused similar IL-10 levels with those released by biofilm-exposed PMNs. CONCLUSIONS: The synergistic, additive or antagonistic effects of DAmB, LAmB or voriconazole on biofilm-exposed PMNs are organism-specific, with FSSC exhibiting greater resilience than S. apiospermum to antifungals. Biofilms of both moulds caused dampened immune responses. The drug-mediated immunomodulating effect on PMNs, evidenced by IL-1ß, enhanced host protective functions.

The Use of Cefiderocol as Salvage Therapy in an Infant Receiving ECMO and Continuous Renal Replacement Therapy.

BACKGROUND: Infections caused by antimicrobial-resistant (AMR) pathogens are increasing worldwide, representing a serious global public health issue with high morbidity and mortality rates The treatment of Pseudomonas aeruginosa (PA) infections has become a significant challenge due to its ability to develop resistance to many of the currently available antibiotics, especially in intensive care unit (ICU) settings. Among the very few therapeutic lines available against extensively drug-resistant (XDR)-PA and/or with difficult-to-treat resistance (DTR)-PA, cefiderocol is an injectable siderophore cephalosporin not licensed for use in pediatric patients. There are only a few case reports and two ongoing trials describing the administration of this cephalosporin in infants. CASE PRESENTATION: This report describes the case of a critically ill 8-month-old girl affected by ventilator-associated pneumonia (VAP) infection complicated by bloodstream infection (BSI) sustained by VIM-producing PA. She was treated with cefiderocol as a salvage therapy during ECMO and CRRT support. CONCLUSIONS: In healthcare settings, treating multidrug-resistant, Gram-negative bacteria poses a serious challenge, especially in pediatric patients. Our findings suggest that cefiderocol can be considered as an off-label rescue therapy in selected pediatric cases.

Daptomycin exerts differential immunomodulatory effects on host responses against methicillin-resistant Staphylococcus aureus biofilms.

Daptomycin (DAP) is indicated for difficult-to-treat Gram-positive infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA). Exposure of S. aureus to subinhibitory antimicrobial concentrations (sub-MICs) has been shown to alter cell morphology and biofilm formation. This study aimed to investigate the influence of DAP biofilm sub-MICs on the damage caused by human polymorphonuclear neutrophils (PMNs) against MRSA biofilms and the potential immunomodulatory activity of DAP on human monocytes (MNCs) exposed to MRSA biofilms. DAP activity against biofilms and the impact of DAP on PMN-induced biofilm damage were evaluated by the XTT reduction assay, whereas pathogen recognition, signal transduction and cytokine modulation of DAP on MNCs in response to MRSA biofilms were assessed by RT-PCR and ELISA methodology. The MIC50 of DAP to MRSA biofilms was 16-32 mg/L. Pre-treatment of MRSA with 1, 2 or 4 mg/L DAP caused a synergistic effect on PMN-mediated biofilm damage, being dependent on the effector-to-target ratio. MNCs responded to MRSA biofilms and DAP through Toll like receptor 2 (TLR2) upregulation and increased NLRP3 inflammasome production. DAP caused 2.5-fold greater TLR2 mRNA levels than those caused by MRSA biofilms. A predominantly inflammatory response was induced by either component, causing the release of significantly increased IFN-γ, TNF-α, IL-8 and IL-6 levels by MNCs exposed to the combination treatment. MRSA biofilms alone or combined with DAP caused low amounts of IL-10 production, but increased IL-1ß levels. DAP may condition MNCs towards an inflammatory response through TLR2 engagement and NLRP3 inflammasome activation, possibly controlling biofilm-associated pathogenicity.

Paediatric cutaneous mucormycosis: A case report and review of the literature.

BACKGROUND: Mucormycosis has emerged as an increasingly important fungal disease for immunocompromised children and neonates, with the cutaneous form being one of its most common presentations. METHODS: We present a cutaneous mucormycosis case in a 10-year-old girl and analyse reports of single cases and case series of cutaneous mucormycosis in ≤16-year-old patients, recorded in PUBMED from 1953 to 2020, for epidemiology, risk factors, diagnostic and therapeutic procedures and outcome. RESULTS: 113 cases were enrolled. Median age was 5 years (Interquartile Range [IQR] 10.9), without gender predominance. Underlying conditions were haematologic malignancies/disorders (25.7%), prematurity (23%), solid organ transplantation (3.5%), diabetes mellitus type 1 (4.4%), immunodeficiency and other diseases (14.2%), and no underlying conditions (29.2%). Inoculation occurred through major trauma (12.4%), including surgery and motor vehicle accidents, catheter sites (27.4%), dressings, patches and probes (11.5%), burns and farm-related accidents (8.8%). Rhizopus spp. was most frequently isolated (43.4%), followed by Lichtheimia corymbifera (9.7%), Saksenaea vasiformis (8%), Mucor and Rhizomucor spp. (5.3% each), other species/combinations (7.2%) and unspecified isolates (21.2%). Surgery was combined with antifungals in 62.8%. Each was performed solely in 27.4% and 6.2%, respectively. Amphotericin B was used in 78% (alone in 55.8% and combined with other antifungals in 22.2%) of the cases. Overall mortality was 26.5%. In regression analysis, prematurity and haematologic malignancies/disorders were associated with increased mortality, whereas combination of antifungals and surgery with improved survival. CONCLUSION: Cutaneous mucormycosis mainly affects premature infants and children with haematologic malignancies/disorders. Outcome is improved when active antifungal therapy and surgery are combined.

A Longitudinal Study of Spontaneous Gut Decolonization of Carbapenem-resistant Gram-negative Bacteria in Neonatal and Pediatric Patients.

BACKGROUND: Antibiotic exposure may convert gut microbiome to reservoir of resistant organisms, including carbapenem-resistant Gram-negative bacteria (CRGNB). Little is known about natural history of spontaneous CRGNB decolonization of neonates/children and their risk to develop CRGNB infections. METHODS: Patients hospitalized in a tertiary care hospital (1 days to 16 years) found to be CRGNB colonized in weekly surveillance cultures during hospitalization (January 2018 to December 2019) were prospectively followed after discharge with monthly rectal cultures for 12 months after colonization until decolonization (3 consecutive negative rectal cultures, ≥1 week apart). Patient demographics, clinical characteristics and CRGNB infections were recorded. Polymerase chain reaction for carbapenemases was performed in patients colonized, after 3 negative cultures, at the day of the last negative and the day of the first new positive culture. RESULTS: One-hundred thirty patients (median age, 1.3 months; lower-upper quartile values, 0.8-6.9 months) were studied including 66 neonates (median age, 12.6 days; Q1-Q3, 5-18.5 days). Among patients >30 days old, 51.6% achieved decolonization within 6 months, and among neonates, 91% achieved decolonization within 6 months. By 12th month, 89% of >30 days and 100% of neonates were decolonized. Forty-four (33.9%) patients (59% >30 days and 9% neonates) developed CRGNB infection(s), mainly pneumonia (25%) and bloodstream infection (20.5%). Prolonged colonization (odds ratio [OR], 7.75; 95% confidence interval [CI], 2.10-28.58), duration of broad-spectrum antibiotic use (OR, 1.22; 95% CI, 1.11-1.34) and parenteral nutrition (OR, 4.53; 95% CI, 1.14-17.94) were associated with the development of CRGNB infection. Two patients (1.5%) were found by polymerase chain reaction colonized after 3 negative cultures. CONCLUSIONS: Spontaneous decolonization occurs in most CRGNB colonized >30 days and all neonates within 12 months. One-third of colonized patients develop CRGNB infection(s). These findings may help optimize duration of contact precautions and empirical antimicrobial therapy for CRGNB colonized pediatric patients.

Activity of Amphotericin B Formulations and Voriconazole, Alone or in Combination, against Biofilms of Scedosporium and Fusarium spp.

Scedosporium and Fusarium species are emerging opportunistic pathogens, causing invasive fungal diseases in humans, particularly in immunocompromised patients. Biofilm-related infections are associated with increased morbidity and mortality. Here, we assessed the ability of Scedosporium apiospermum and Fusarium solani species complex (FSSC) isolates to form biofilms and evaluated the efficacy of deoxycholate amphotericin B (D-AMB), liposomal amphotericin B (L-AMB), and voriconazole (VRC), alone or in combination, against mature biofilms. Biofilm formation was assessed by safranin staining and spectrophotometric measurement of optical density. Planktonic and biofilm damage was assessed by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] reduction assay. Planktonic cell and biofilm MIC50s were determined as the minimum concentrations that caused ≥50% fungal damage compared to untreated controls. The combined activity of L-AMB (0.5 to 32 mg/liter) and VRC (0.125 to 64 mg/liter) against biofilms was determined by the checkerboard microdilution method and analyzed by the Bliss independence model. Biofilm MIC50s of D-AMB and L-AMB against S. apiospermum isolates were 1 and 2 mg/liter and against FSSC isolates were 0.5 and 1 mg/liter, respectively. Biofilm MIC50s of VRC against S. apiospermum and FSSC were 32 mg/liter and >256 mg/liter, respectively. Synergistic effects were observed at 2 to 4 mg/liter of L-AMB combined with 4 to 16 mg/liter of VRC against S. apiospermum biofilms (mean ΔE ± standard error, 17% ± 3.7%). Antagonistic interactions were found at 0.5 to 4 mg/liter of L-AMB combined with 0.125 to 16 mg/liter of VRC against FSSC isolates, at -28% ± 2%. D-AMB and L-AMB were more efficacious against S. apiospermum and FSSC biofilms than VRC.

Covid-19: Face Mask Protection in the Pediatric Setting.

We report our experience regarding a pediatric patient-case who had a covid-19 infection, which was initially considered a common viral infection and was managed accordingly for the first 36 hours while being hospitalized. Wearing a simple surgical face mask was the only protective measure which our personnel has adopted. All staff members were tested for covid-19 infection with swab specimens from the nasopharynx and pharynx and were found to be negative in 7-10 days after coming into contact with the patient. Thirty-one days after contact with the covid-19 patient, no one of the staff members had respiratory symptoms, and therefore, they all returned to work. This case shows the importance of face-mask wearing to prevent the transmission various of respiratory infections, including that caused by the novel SARS-CoV-2 microorganism.

Population Pharmacokinetics and Outcomes of Critically Ill Pediatric Patients Treated with Intravenous Colistin at Higher Than Recommended Doses.

Limited pharmacokinetic (PK) data suggest that currently recommended pediatric dosages of colistimethate sodium (CMS) by the Food and Drug Administration and European Medicines Agency may lead to suboptimal exposure, resulting in plasma colistin concentrations that are frequently <2 mg/liter. We conducted a population PK study in 17 critically ill patients 3 months to 13.75 years (median, 3.3 years) old who received CMS for infections caused by carbapenem-resistant Gram-negative bacteria. CMS was dosed at 200,000 IU/kg/day (6.6 mg colistin base activity [CBA]/kg/day; 6 patients), 300,000 IU/kg/day (9.9 mg CBA/kg/day; 10 patients), and 350,000 IU/kg/day (11.6 mg CBA/kg/day; 1 patient). Plasma colistin concentrations were determined using ultraperformance liquid chromatography combined with electrospray ionization-tandem mass spectrometry. Colistin PK was described by a one-compartment disposition model, including creatinine clearance, body weight, and the presence or absence of systemic inflammatory response syndrome (SIRS) as covariates (P < 0.05 for each). The average colistin plasma steady-state concentration (Css,avg) ranged from 1.11 to 8.47 mg/liter (median, 2.92 mg/liter). Ten patients had Css,avg of ≥2 mg/liter. The presence of SIRS was associated with decreased apparent clearance of colistin (47.8% of that without SIRS). The relationship between the number of milligrams of CBA per day needed to achieve each 1 mg/liter of plasma colistin Css,avg and creatinine clearance (in milliliters per minute) was described by linear regression with different slopes for patients with and without SIRS. Nephrotoxicity, probably unrelated to colistin, was observed in one patient. In conclusion, administration of CMS at the above doses improved exposure and was well tolerated. Apparent clearance of colistin was influenced by creatinine clearance and the presence or absence of SIRS.

Immunomodulatory effects of colistin on host responses against carbapenem-resistant Klebsiella pneumoniae biofilms.

Colistin (CST) is a last-resort therapeutic option for carbapenem-resistant Klebsiella pneumoniae (CR-Kp) infections in critically ill patients. The effect of subinhibitory CST concentrations (sub-MICs) on biofilm formation is organism-dependent. We investigated the interactions between CST and innate immune cells against CR-Kp biofilms (CR-KpBF) by studying the effect of biofilm sub-MICs of CST on (i) damage induced by human polymorphonuclear neutrophils (PMNs) on CR-KpBF and (ii) the immunomodulatory potential on human mononuclear cells (MNCs) exposed to CR-KpBF. The impact of CST on PMN-induced biofilm damage was assessed by XTT reduction assay. Signal transduction and gene expression profiles in response to CST sub-MICs of MNCs exposed to CR-KpBF were studied by RT-PCR and multiplex ELISA. Pre-exposure of CR-Kp to 0.06 mg/L CST led to subsequent increased PMN-mediated biofilm damage against CR-KpBF in the presence of CST biofilm sub-MICs: there was an additive effect at 2, 4, 8 and 16 mg/L. However, the overall biofilm damage was not >52%. MNCs responded to CR-KpBF through Toll-like receptor 2 (TLR2) by 2.5-fold upregulation and NLRP3 inflammasome activation. CR-KpBF stimulated increased production of interleukin 1-beta (IL-1ß), tumour necrosis factor-alpha (TNFα), IL-8 and IL-6. In the combination treatment, 0.5 mg/L CST reduced IL-1ß, TNFα and IL-8 levels, whereas at 2 mg/L and 8 mg/L it increased the anti-inflammatory cytokine IL-10 (P < 0.05). Biofilm sub-MICs of CST enhance PMN killing capacity and attenuate production of inflammatory cytokines by MNCs exposed to CR-KpBF, playing a potentially important immunotherapeutic role especially for patients with cytokine deregulation.

Renal mycetomas in a 10-month-old female infant without immunodeficiency.

Candida albicans is the most prevalent and pathogenic fungal infection of the urinary tract. Although fungal urinary tract infections occur less frequently than bacterial infections, their incidence has increased during the last decades. Prematurity, parenteral nutrition, corticosteroids, immunosuppressive factors, surgical procedures, and prolonged antibiotic therapy are common predisposing factors. We report a case of candidal renal mycetomas in a 10-month-old female infant without immunodeficiency who developed candidal infection after surgical treatment for bilateral vesico-ureteric reflux. The renal candidiasis was treated successfully with fluconazole and echinocandin. The occurrence of mycetomas or fungus balls in patients who are immunocompetent is extremely rare. To the best of our knowledge, this is the second case report of mycetomas occurring in immunocompetent pediatric patients.

Forecasting models of infections due to carbapenem-resistant Gram-negative bacteria in an intensive care unit in an endemic area.

OBJECTIVES: The aim of this study was to forecast the monthly incidence rates of infections [infections/1000 bed-days (IBD)] due to carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Acinetobacter baumannii (CRAB) and total carbapenem-resistant Gram-negative bacteria (CRGNB) in an endemic intensive care unit (ICU) during the subsequent year (December 2016-December 2017) following the observational period. METHODS: A 52-month observational period (August 2012-November 2016) was used. Two forecasting models, including a simple seasonal model for CRGNB, CRKP and CRPA and Winters' additive model for CRAB infections, were applied. RESULTS: The models predicted the highest infection rates for CRKP, CRAB and CRGNB in January and September 2017 (23.8/23.4, 24.6/28.5 and 46.8/46.7 IBD, respectively) and for CRPA in February and March 2017 (8.3 and 7.9, respectively). The highest observed rates for CRKP, CRAB and CRGNB were indeed in January and September 2017 (25.6/19.0, 34.2/23.8 and 59.8/42.8 IBD, respectively); and for CRPA in February and March of the same year (15.2 and 12.7, respectively). The increased rates may be associated with personnel's annual work programme and behavioural factors. CONCLUSION: Forecasting models in endemic ICUs may assist in implementation strategies for infection control measures.

Epstein-Barr Encephalitis in a Child with Congenital Human Immunodeficiency Virus Infection: A Case Report Calling for No Forgetfulness.

BACKGROUND: In resource-rich settings, the rate of mother-to-child transmission of human immunodeficiency virus (HIV) has dramatically decreased by virtue of a combination of preventive strategies during the last two decades. CASE PRESENTATION: We present a case of progressive developmental milestone loss in a toddler with previously unknown congenitally acquired human immunodeficiency virus (HIV) infection, complicated by an Epstein-Barr virus (EBV) coinfection. CONCLUSION: Our report underscores the differential diagnosis between HIV encephalopathy and EBV encephalitis and the vertical transmission of the HIV infection, which constitutes an alarming issue in terms of public health.

Thiamine Deficiency in a Child with Short Bowel Syndrome and Review.

Thiamine (vitamin B1) is a water-soluble vitamin that is not endogenously synthesized in humans. It is absorbed by the small intestine, where it is activated. Its active form acts as a coenzyme in many energy pathways. We report a rare case of thiamine deficiency in a 3.5-year old boy with short bowel syndrome secondary to extensive bowel resection due to necrotizing enterocolitis during his neonatal age. The patient was parenteral nutrition-dependent since birth and had suffered from recurrent central catheter-related bloodstream infections. He developed confusion with disorientation and unsteady gait as well as profound strabismus due to bilateral paresis of the abductor muscle. Based on these and a very low thiamine level he was diagnosed and treated for Wernicke encephalopathy due to incomplete thiamine acquisition despite adequate administration. He fully recovered after thiamine administration. After 1999 eight more cases have been reported in the PubMed mostly of iatrogenic origin.

Effects of an Active Surveillance Program and Enhanced Infection Control Measures on Carbapenem-Resistant Gram-Negative Bacterial Carriage and Infections in Pediatric Intensive Care.

We evaluated the effects of enhanced infection control measures (ICMs) on carriage and infections of carbapenem-resistant Gram-negative bacteria (CRGNB) in a pediatric intensive care unit. We conducted a quasi-experimental study, including patients with infections of CRGNB retrospectively for 13 months and those participating in an active surveillance program prospectively for 22 months. Active surveillance (weekly rectal swabs) was implemented during a 63-week subperiod with standard ICMs and a subsequent 27-week subperiod with enhanced ICMs (intensified ICMs supplemented with audits and feedback). Prevalence, colonization pressure, incidence, and infections of CRGNB and compliance with ICMs and enhanced ICMs were recorded. Evaluation of results was performed using time series (TS) and interrupted TS. Compliance with hand hygiene improved during the second subperiod of active surveillance compared with the first; prevalence, colonization pressure, and incidence of CRGNB decreased significantly. The linear trend of centered moving average for carbapenem-resistant Klebsiella pneumoniae (CRKP) decreased from 1.2 to 0.1 infections/1,000 bed-days (IBD) (p = 0.046), while it remained unchanged for carbapenem-resistant Acinetobacter baumannii (CRAB) and increased for carbapenem-resistant Pseudomonas aeruginosa (CRPA) from 0.0 to 2.1 IBD (p < 0.001). Enhanced ICMs can reduce CRKP infections in endemic units, in contrast to CRPA and CRAB infections, which are more difficult to eradicate.

Polyclonal predominance of concurrently producing OXA-23 and OXA-58 carbapenem-resistant Acinetobacter baumannii strains in a pediatric intensive care unit.

We report a predominance (64.7%) of polyclonal carbapenem-resistant Acinetobacter baumannii (CRAB) strains concurrently producing OXA-23 and OXA-58 carbapenemases in a pediatric intensive care unit in an endemic area. This is the first report of emergence of such double-OXA CRAB strains in a single unit worldwide.

Dose-Dependent Synergistic Interactions of Colistin with Rifampin, Meropenem, and Tigecycline against Carbapenem-Resistant Klebsiella pneumoniae Biofilms.

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) can cause biofilm-related bloodstream infections associated with significant morbidity and mortality worldwide. We investigated the bactericidal activities of colistin (CST), rifampin (RIF), meropenem (MEM), gentamicin (GEN), and tigecycline (TGC) alone and that of CST in combination with RIF, MEM, GEN, or TGC against CR-Kp mature biofilms. Twenty CR-Kp blood isolates were derived from an equal number of bloodstream infections in adult patients. Biofilm formation was assessed by staining with 0.4% crystal violet and measuring the optical density spectrophotometrically at 545 nm. Biofilm damage was measured as the percent reduction of metabolic activity by an XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] assay. The MIC50 for biofilms was determined as the minimum concentration that caused ≥50% bacterial damage compared to that for untreated controls. Antibacterial drug interactions were analyzed by the Bliss independence model. Four of the 20 CR-Kp isolates were biofilm producers. Biofilm MIC50s of CST, RIF, MEM, GEN, and TGC for these isolates were 64, 8, >256, 128, and 8 mg/liter, respectively. Synergistic interactions were observed at 32 to 64 mg/liter of CST combined with 0.25 to 4 mg/liter of RIF, at 32 mg/liter of CST combined with 0.007 to 0.25 mg/liter of MEM, and at 16 to 32 mg/liter of CST combined with 16 to 64 mg/liter of TGC. The synergy was highest for CST plus RIF, with a mean ΔE ± standard error (SE) of 49.87% ± 9.22%, compared to 29.52% ± 4.97% for CST plus MEM (P < 0.001) and 32.44% ± 6.49% for CST plus TGC (P < 0.001). Indifferent results were exhibited by CST plus GEN. None of the combinations exhibited antagonism. These drug interaction findings, especially those for CST with RIF, may be of importance in the treatment of biofilm-related CR-Kp infections.

Efficacy and Safety of Echinocandins for the Treatment of Invasive Candidiasis in Children: A Meta-analysis.

BACKGROUND: Echinocandins are recommended for the treatment of suspected or confirmed invasive candidiasis (IC) in adults. Less is known about the use of echinocandins for the management of IC in children. The aim of this study was to investigate the overall efficacy and safety of echinocandin class in neonatal and pediatric patients with IC. METHODS: PubMed, Cochrane Central, Scopus and Clinical trial registries were searched up to July 27, 2017. Eligible studies were randomized controlled trials that evaluated the efficacy and safety of any echinocandin versus agents of other antifungal classes for the treatment of IC in pediatric patients. The primary outcome was treatment success with resolution of symptoms and signs, and absence of IC. In the meta-analysis a random effects model was used, and the odds ratio (OR) and 95% confidence intervals (CIs) were calculated. RESULTS: Four randomized clinical trials (324 patients), 2 confirmed IC (micafungin vs. liposomal amphotericin B (L-AmB) and caspofungin vs. L-AmB) and 2 empirical therapy trials (caspofungin vs. deoxycholate amphotericin B and caspofungin vs. L-AmB) were included. There was no significant difference between echinocandins and comparator in terms of treatment success (OR = 1.61, 95% CI: 0.74-3.50) and incidence of treatment-related adverse events (OR = 0.70, 95% CI: 0.39-1.26). However, fewer children treated with echinocandins discontinued treatment because of adverse events than amphotericin B formulations (OR = 0.26, 95% CI: 0.08-0.82, P = 0.02). CONCLUSIONS: In the treatment of IC in children, echinocandins show non-inferior efficacy compared with amphotericin B formulations with fewer discontinuations than in comparator arm.

Molecular Epidemiology of Endemic Carbapenem-Resistant Gram-Negative Bacteria in an Intensive Care Unit.

The molecular epidemiology of endemic carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB) in an intensive care unit located in an endemic area with high rates of resistance was investigated. A CRPA strain producing VIM and KPC concurrently was detected for the first time in an endemic area. CRKP strains producing K. pneumoniae carbapenemase predominated and were mainly assigned to the "hyperepidemic Greek clone." Predominant OXA-23-like producing CRAB strains were assigned to multiple pulsotypes.