Alberta Collaborative Quality Improvement Strategies to Improve Outcomes of Moderate and Late Preterm Infants (ABC-QI) Trial: a protocol for a multicentre, stepped-wedge cluster randomized trial.

BACKGROUND: Evidence-based Practice for Improving Quality (EPIQ) is a collaborative quality improvement method adopted by the Canadian Neonatal Network that led to decreased mortality and morbidity in very preterm neonates. The Alberta Collaborative Quality Improvement Strategies to Improve Outcomes of Moderate and Late Preterm Infants (ABC-QI) Trial aims to evaluate the impact of EPIQ collaborative quality improvement strategies in moderate and late preterm neonates in Alberta, Canada. METHODS: In a 4-year, multicentre, stepped-wedge cluster randomized trial involving 12 neonatal intensive care units (NICUs), we will collect baseline data with the current practices in the first year (all NICUs in the control arm). Four NICUs will transition to the intervention arm at the end of each year, with 1 year of follow-up after the last group transitions to the intervention arm. Neonates born at 32 + 0 to 36 + 6 weeks' gestation with primary admission to NICUs or postpartum units will be included. The intervention includes implementation of respiratory and nutritional care bundles using EPIQ strategies, including quality improvement team building, quality improvement education, bundle implementation, quality improvement mentoring and collaborative networking. The primary outcome is length of hospital stay; secondary outcomes include health care costs and short-term clinical outcomes. Neonatal intensive care unit staff will complete a survey in the first year to assess quality improvement culture in each unit, and a sample will be interviewed 1 year after implementation in each unit to evaluate the implementation process. INTERPRETATION: The ABC-QI Trial will assess whether collaborative quality improvement strategies affect length of stay in moderate and late preterm neonates. It will provide detailed population-based data to support future research, benchmarking and quality improvement. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT05231200.

Comparing Three Methods of Therapeutic Hypothermia Among Transported Neonates with Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) and associated multiorgan injury are significant causes of morbidity and mortality in term and near-term neonates. Therapeutic hypothermia (TH) is the current standard of care for neuroprotection in neonates with HIE. In our experience, the majority of babies born with HIE were found in nontertiary care facilities in our region, where effective methods of cooling during transport to tertiary care centers are desirable. Most centers initiate passive TH at referral hospitals, while active cooling is typically initiated during transport. The objective of this study was to evaluate the effectiveness of three methods of cooling during transport of neonates with HIE in southern Alberta. In this prospective cohort study, 186 neonates with HIE were transported between January 2013 and December 2021. Among the 186 neonates, 47 were passively cooled, 36 actively cooled with gel packs, and 103 cooled with a servo-controlled cooling device. The clinical characteristics were comparable for the three groups, with no difference in adverse events. Fifteen neonates (8%) died and 54 neonates (29%) suffered radiologically determined brain injury. Servo-controlled cooling was found to be superior to other methods in maintaining a target temperature without significant fluctuation during transport and with temperature in the target range on arrival at tertiary care facilities. The rate of overcooling was also lower in the servo-controlled group compared with other groups. There were no statistically significant differences between the groups in relation to mortality and brain MRI changes associated with HIE. Adjusting for GA, 10-minute Apgar score, base excess, HIE stage, and need for intubation during transport, passive cooling increased the odds of temperature fluctuation outside the range by 12-fold and gel pack cooling by 13-fold compared with servo-controlled cooling. The use of servo-controlled TH devices should be the preferred practice wherever feasible. (REB17-1334_REN3).

The Utility of Simulation-Based Training in Teaching Frontline Providers Modified Sarnat Encephalopathy Examination: A Randomized Controlled Pilot Trial.

BACKGROUND: Limited training in targeted neurological examination makes it challenging for frontline providers to identify newborns with perinatal asphyxia eligible for therapeutic hypothermia. This training is important in the era of telemedicine, where the experts can remotely guide further care of these newborns. METHODS: This randomized controlled pilot study was conducted in a South Indian tertiary hospital. Neonatal nurses, who had no previous hands-on experience in MSEE, were trained in modified Sarnat staging by a didactic teaching session using online teaching module. The nurses were then randomized into two groups for hands-on demonstration by the same trainer (low-fidelity mannequin versus a healthy term newly born infant). After the training period, MSEEs of a normal newborn were performed independently by nurses and were video recorded and assessed by three blinded neonatologists with expertise in neonatal neurology. A follow-up examination was performed by the same nurses after three months to assess skill retention. RESULTS: The 10 global ratings of the components of the MSEE were comparable among both groups in both initial and follow-up assessments. The overall diagnostic value was comparable between the simulation and traditional groups (93.75%, 94.11%, respectively). Follow-up examination after three months showed better skill retention in the simulation group (84%) compared with the traditional group (66.7%). CONCLUSIONS: Online-based and low-fidelity mannequin training was equally effective as the traditional method of teaching MSEE in term neonates.

Neuroprotection care bundle implementation is associated with improved long-term neurodevelopmental outcomes in extremely premature infants.

OBJECTIVE: To study the impact of an evidence-based neuroprotection care (NPC) bundle on long-term neurodevelopmental impairment (NDI) in infants born extremely premature. STUDY DESIGN: An NPC bundle targeting predefined risk factors for acute brain injury in extremely preterm infants was implemented. We compared the incidence of composite outcome of death or severe neurodevelopmental impairment (sNDI) at 21 months adjusted age pre and post bundle implementation. RESULTS: Adjusting for confounding factors, NPC bundle implementation associated with a significant reduction in death or sNDI (aOR, 0.34; 95% CI 0.17-0.68; P = 0.002), mortality (aOR, 0.31; 95% CI (0.12-0.79); P = 0.015), sNDI (aOR, 0.37; 95% CI: 0.12-0.94; P = 0.039), any motor, language, or cognitive composite score <70 (aOR, 0.48; 95% CI: 0.26-0.90; P = 0.021). CONCLUSION: Implementation of NPC bundle targeting predefined risk factors is associated with a reduction in mortality or sNDI in extremely preterm infants.

Impact of quality improvement outreach education on the incidence of acute brain injury in transported neonates born premature.

OBJECTIVE: To evaluate impact of a quality improvement (QI) outreach education on incidence of acute brain injury in transported premature neonates. STUDY DESIGN: Neonates born at <33 weeks gestation outside the tertiary center were included. The QI intervention was a combination of neuroprotection care bundle, in-person visits, and communication system improvement. Descriptive and regression (adjusting for Gestational Age, Birth Weight, Gender, and antenatal steroids, Mode of delivery, Apgars at 5 minutes, Prophylactic indomethacin, PDA, and Inotropes use) analyses were performed. The primary outcome was a composite of death and/or severe brain injury on cranial ultrasound using a validated classification. RESULTS: 181 neonates studied (93 before and 88 after). The rate and adjusted odds of death and/or severe brain injury reduced significantly post intervention (30% vs 15%) and (AOR 0.36, 95%CI, 0.15-0.85, P = 0.02) respectively. CONCLUSION: Implementation of outreach education targeting neuroprotection can reduce acute brain injury in transported premature neonates.

Hemodynamic Quality Improvement Bundle to Reduce the Use of Inotropes in Extreme Preterm Neonates.

BACKGROUND: We evaluated the effect of the quality improvement (QI) bundle on the rate of inotrope use and associated morbidities. METHODS: We included inborn preterm neonates born at < 29 weeks admitted to level III NICU. We implemented a QI bundle focusing on the first 72 h from birth which included delayed cord clamping, avoidance of routine echocardiography, the addition of clinical criteria to the definition of hypotension, factoring iatrogenic causes of hypotension, and standardization of respiratory management. The rate of inotropes use was compared before and after implementing the care bundle. Incidence of cystic periventricular leukomalacia (cPVL) was used as a balancing measure. RESULTS: QI bundle implementation was associated with significant reduction in overall use of inotropes (24 vs 7%, p < 0.001), dopamine (18 vs 5%, p < 0.001), and dobutamine (17 vs 4%, p < 0.001). Rate of acute brain injury decreased significantly: acute brain injury of any grade (34 vs 20%, p < 0.001) and severe brain injury (15 vs 6%, p < 0.001). There was no difference in the incidence of cPVL (0.8 vs 1.4%, p = 0.66). Associations remained significant after adjusting for confounding factors. CONCLUSIONS: A quality improvement bundled approach resulted in a reduction in inotropes use and associated brain morbidities in premature babies.

Feeding during therapeutic hypothermia is safe and may improve outcomes in newborns with perinatal asphyxia.

OBJECTIVE: We assessed the impact of early enteral feeding introduction during therapeutic hypothermia on time to reach full enteral feeding (FEF) and other feeding related outcomes in infants born at ≥35 weeks gestational age and diagnosed with moderate to severe Hypoxic-Ischemic Encephalopathy. METHODS: A prospective cohort with historical control study, conducted on infants admitted to the Alberta Children's Hospital level III NICU in Calgary between January 2013 and December 2018. Infants were divided into 2 groups: (1) unfed group (UG), which was kept nil per os during the 72 h of therapeutic Hypothermia (TH), with subsequent introduction of feeding and gradual increase to FEF; (2) fed group (FG), which received feeding at 10 mL/kg/day during TH then increased gradually to FEF. Groups were compared for time to FEF and the type of milk they were being fed on discharge. Other gut related health risks such as NEC and sepsis were examined. RESULTS: During the study period, 146 infants received therapeutic hypothermia, of whom 75 in the UG and 71 in the FG. The FG compared to the UG received the first feed sooner after TH initiation (median 57 vs. 86.5 h, p < .001), reached FEF earlier (median 6 vs. 8 days, p = .012), had a higher rate of being fully fed in the first week of life (70 vs. 53%, p < .035), was kept NPO for shorter duration (median 2 vs. 4 days, p < .001), and had a higher rate of breast milk feeding at discharge (41 vs. 13%, p < .001). There were no cases of necrotizing enterocolitis or late onset sepsis in either group during the hospital stay. CONCLUSION: Minimal enteral feeding during therapeutic hypothermia appears to be safe and leads to a shorter time to FEF and higher rates of breast milk feeding at discharge.

Impact of outreach education program on outcomes of neonates with hypoxic ischemic encephalopathy.

AIM: To evaluate the impact of outreach education targeting neuroprotection on outcomes of outborn infants with moderate-to-severe hypoxic ischemic encephalopathy (HIE). METHODS: A retrospective cohort study of infants admitted with moderate-to-severe HIE was conducted following the implementation of outreach education in January 2016. Key interventions were early identification and referral of infants with encephalopathy utilizing telemedicine and a centralized communication system, hands-on simulation, and interactive case discussion and dissemination of clinical management guidelines and educational resources. The association between the intervention and a composite outcome of death and/or severe brain injury on brain magnetic resonance imaging (MRI) was tested controlling for the confounding factors. RESULTS: Of 165 neonates, 37 (22.4%) died and/or had a severe brain injury. This outcome decreased from 35% (27/77) to 11% (10/88) following the implementation of outreach education (P<0.001). Eligible infants not undergoing therapeutic hypothermia within 6 hours from birth decreased from 19.5% (15/77) to 4.5% (4/88). The use of inotropes decreased from 49.3% (38/77) to 19.6% (13/88). Any core temperature below 33°C was recorded for 20/53 (38%) before and 16/78 (21%) after, while those within the target range of 33°C to 34°C at admission to a tertiary care facility increased from (15/53) 28% to (51/88) 58%. Outreach education was independently associated with decreased composite outcome of death and/or severe brain injury on MRI (adjusted odds ratio 0.2; 95% confidence interval 0.07 to 0.52). CONCLUSION: Outreach education targeting neuroprotection for infants with moderate-to-severe HIE was associated with a reduction in death and/or severe brain injury.

Does a Split-Week Gestational Age Model Provide Valuable Information on Neurodevelopmental Outcomes in Extremely Preterm Infants?

Our primary objective for this follow-up study was to compare the neurodevelopmental outcomes of a surviving cohort of infants using a split-week gestational model (early versus late) gestational age (GA) and the standard completed GA categorization. Neurodevelopmental outcomes using a split-week GA model defined as early (X, 0-3) and late (X, 4-6), with X being 23-26 weeks GA, were compared to outcomes using completed weeks GA. In total, 1012 infants were included in the study. Statistically significant differences were noted in outcomes between the early and late split of the gestational week at 23 weeks (early vs. late), with 13.3% vs. 54.5% for no neurodevelopmental impairment, and 53.3% vs. 22.7% for significant impairment (p = 0.034), respectively. There were no differences seen in the split week model for 24, 25, and 26 weeks. A trend towards improved neurodevelopmental outcomes was seen with each increasing gestation week. The split-week model did not provide additional information for pregnancies and infants between 24 and 26 weeks gestation. It did, however, provide information for counsel for infants at 23 weeks gestation, showing benefits in the late versus early half of the week.

Cord Blood Cytokine Levels Correlate With Types of Placental Pathology in Extremely Preterm Infants.

Background: Placental abnormalities are associated with inflammation and have been linked to brain injury in preterm infants. We studied the relationship between placental pathology and the temporal profiles of cytokine levels in extremely pre-term infants. Study Design: We prospectively enrolled 55 extremely preterm infants born between June 2017 and July 2018. Levels of 27 cytokines were measured in blood drawn from the umbilical artery at birth and from infants at 1-3 and 21-28 days of life. Placental pathology was grouped as normal (N), inflammation (I), vasculopathy (V), or combined vasculopathy and inflammation (V+I). Results: Complete data was available from 42 patients. Cord blood median levels of cytokines differed between groups with the highest levels observed in group V+I as compared to groups N, I and V for the following: Eotaxin (p = 0.038), G-CSF (p = 0.023), IFN-γ (p = 0.002), IL-1ra (p < 0.001), IL-4 (p = 0.005), IL-8 (p = 0.010), MCP-1 (p = 0.011), and TNFα (p = 0.002). Post-hoc analysis revealed sex differences between and within the placental pathology groups. Conclusion: Specific types of placental pathology may be associated with differential cytokine profiles in extremely pre-term infants. Sampling from cord blood may help assess the pathological status of the placenta and potentially infer outcome risks for the infant.

Consensus Approach for Standardizing the Screening and Classification of Preterm Brain Injury Diagnosed With Cranial Ultrasound: A Canadian Perspective.

Acquired brain injury remains common in very preterm infants and is associated with significant risks for short- and long-term morbidities. Cranial ultrasound has been widely adopted as the first-line neuroimaging modality to study the neonatal brain. It can reliably detect clinically significant abnormalities that include germinal matrix and intraventricular hemorrhage, periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation, cerebellar hemorrhage, and white matter injury. The purpose of this article is to provide a consensus approach for detecting and classifying preterm brain injury to reduce variability in diagnosis and classification between neonatologists and radiologists. Our overarching goal with this work was to achieve homogeneity between different neonatal intensive care units across a large country (Canada) with regards to classification, timing of brain injury screening and frequency of follow up imaging. We propose an algorithmic approach that can help stratify different grades of germinal matrix-intraventricular hemorrhage, white matter injury, and ventricular dilatation in very preterm infants.

Post-hemorrhagic ventricular dilatation: inter-observer reliability of ventricular size measurements in extremely preterm infants.

BACKGROUND: Post-hemorrhagic ventricular dilatation (PHVD) in preterm infants can be assessed with ventricular size indices from cranial ultrasound. We explored inter-observer reliability of these indices for prediction of severe PHVD. METHODS: For all 139 infants with IVH, serial neonatal ultrasound at 3 time points (days 4-7, day 14, 36 weeks PMA) were assessed independently by 3 observers with differing levels of training/experience. Ventricular index (VI), anterior horn width (AHW), and fronto-temporal horn ratio (FTHR) were measured and used to diagnose PHVD. For all, inter-observer reliability and predictive values for receipt of surgical intervention were calculated. RESULTS: Inter-observer reliability for all observers varied from poor to excellent, with higher reliability for VI/AHW (ICC 0.49-0.84/0.51-0.81) than FTHR (0.41-0.82), particularly from the second week. Good-excellent inter-expertise reliability was found between observers with ample experience/training (0.65-0.99), particularly for VI and AHW, while poor-moderate when comparing with an inexperienced observer (0.28-0.88). Slightly higher predictive value for PHVD intervention (n = 12) was found for AHW (AUC 0.86-0.96) than for VI and FTHR (0.80-0.96/0.80-0.95). CONCLUSIONS: AHW and VI are highly reproducible in experienced hands compared to FTHR, with AHW from the second week onwards being the strongest predictor for receiving surgical intervention for severe PHVD. AHW may aid in early PHVD diagnosis and decision-making on intervention. IMPACT: While ventricular size indices from serial cUS are superior to clinical signs of increased intracranial pressure to assess PHVD, questions remained on their inter-observer reproducibility and reliability to predict severity of PHVD. AHW and VI are highly reproducible when performed by experienced clinicians. AHW from the second week of birth is the strongest predictor of PHVD onset and severity. AHW, combined with VI, may aid in early PHVD diagnosis and decision-making on need for surgical intervention. Consistent use of these indices has the potential to improve PHVD management and therewith the long-term outcomes in preterm infants.

Neuroprotection Care Bundle Implementation to Decrease Acute Brain Injury in Preterm Infants.

BACKGROUND: We assessed the impact of an evidence-based neuroprotection care bundle on the risk of brain injury in extremely preterm infants. METHODS: We implemented a neuroprotection care bundle consisting of a combination of neuroprotection interventions such as minimal handling, midline head position, deferred cord clamping, and protocolization of hemodynamic and respiratory managements. These interventions targeted risk factors for acute brain injury in extremely preterm infants (born at gestational age less than 29 weeks) during the first three days of birth. Implementation occurred in a stepwise manner, including care bundle development by a multidisciplinary care team based on previous evidence and experience, standardization of outcome assessment tools, and education. We compared the incidence of the composite outcome of acute preterm brain injury or death preimplementation and postimplementation. RESULTS: Neuroprotection care bundle implementation associated with a significant reduction in acute brain injury risk factors such as the use of inotropes (24% before, 7% after, P value < 0.001) and fluid boluses (37% before, 19% after, P value < 0.001), pneumothorax (5% before, 2% after, P value = 0.002), and opioid use (19% before, 7% after, P value < 0.001). Adjusting for confounding factors, the neuroprotection care bundle significantly reduced death or severe brain injury (adjusted odds ratio, 0.34; 95% confidence interval, 0.20 to 0.59; P value < 0.001) and severe brain injury (adjusted odds ratio, 0.31; 95% confidence interval, 0.17 to 0.58; P < 0.001). CONCLUSIONS: Implementation of neuroprotection care bundle targeting predefined risk factors is feasible and effective in reducing acute brain injury in extremely preterm infants.

Split-week gestational age model provides valuable information on outcomes in extremely preterm infants.

AIM: To compare composite outcomes of neonatal mortality or morbidity using a split-week gestational age (GA) model to completed weeks GA maturity at 23-26 weeks gestation. METHODS: This was a retrospective cohort study of infants born at 23-26 weeks GA. Outcomes using a split-week GA model defined as early (X, 0-3) and late (X, 4-6) with X being 23-26 weeks GA were compared to outcomes using completed weeks GA, with a similar comparison between the late split of the preceding week (X, 4-6) and early split of the subsequent week (X + 1, 0-3). RESULTS: A total of 1345 infants were included in the study. Statistically significant differences were noted in outcomes between the early and late split of the gestational week at 24 (early vs late, 85.6% vs 73.0%), 25 (69.6% vs 56.6%) and 26 weeks (55.9% vs 37.4%), but not at 23 weeks GA (95.2% vs 94.5%). No statistically significant differences were noted between the late vs early part of the subsequent week (23, 4-6) vs (24, 0-3), and (24, 4-6) vs (25, 0-3) GA. CONCLUSION: Neonatal outcome estimates using a split week model differs from that based on the use of completed weeks of gestational maturity.

Implementation of Neonatal Neurocritical Care Program Improved Short-Term Outcomes in Neonates With Moderate-to-Severe Hypoxic Ischemic Encephalopathy.

BACKGROUND: Despite the introduction of therapeutic hypothermia, infants with moderate-to-severe hypoxic-ischemic encephalopathy remain at risk of mortality and morbidity. A dedicated service with standardized management protocols and improved communication may help improve care. We aimed to evaluate the impact of a dedicated neonatal neurocritical care service on short-term outcomes in infants with hypoxic-ischemic encephalopathy. METHODS: We performed a retrospective cohort study (July 2008 to December 2017) on term and near-term infants admitted to two tertiary neonatal intensive care units with moderate-to-severe hypoxic-ischemic encephalopathy, before and after neonatal neurocritical care service implementation. The primary outcome was brain magnetic resonance imaging findings consistent with those of hypoxic-ischemic encephalopathy. Secondary outcomes included the cooling initiation rate, hospital stay duration, antiseizure medication use, and inotrope use. Regression analysis and interrupted time series analysis were performed after adjusting for confounding factors. RESULTS: In total, 216 infants with moderate-to-severe hypoxic-ischemic encephalopathy were analyzed-109 before and 107 after neonatal neurocritical care implementation. After adjusting for confounding factors, there was a significant reduction in primary outcomes (adjusted odds ratio: 0.3, confidence interval: 0.15 to 0.57, P < 0.001) after neonatal neurocritical care implementation. Average hospital stay duration reduced by 5.2 days per infant (P = 0.03), identification of eligible infants for cooling improved (P < 0.001), antiseizure medication use reduced (P = 0.001), and early inotropes use reduced (P = 0.04). CONCLUSION: Implementation of a neonatal neurocritical care service associated with decreased brain injury shortened the hospital stay duration and improved the care of infants with moderate-to-severe hypoxic-ischemic encephalopathy.

Elective transfers of preterm neonates to regional centres on non-invasive respiratory support is cost effective and increases tertiary care bed capacity.

AIM: Managing capacity at regional facilities caring for sick neonates is increasingly challenging. This study estimated the clinical and economic impact of the elective transfer of stable infants requiring nasal continuous positive airway pressure (NCPAP) from level three to level two neonatal intensive care units (NICUs) within an established clinical network of five NICUs. METHODS: We retrospectively analysed the records of 99 stable infants transferred on NCPAP between two level three NICUs and three level two NICUs in Calgary, Canada, between June 2014 and May 2016. RESULTS: The median gestational age and weight at birth were 28 weeks and 955 g, and the median corrected gestational age and weight at transfer were 33 weeks and 1597 g, respectively. This resulted in cost savings of $2.65 million Canadian dollars during the two-year study period, and 848 level three NICU days were freed up for potentially sick neonates. There were no adverse events associated with the transfers. CONCLUSION: The elective transfer of stable neonates on NCPAP from level three to level two NICUs within an established clinical network led to substantial cost savings, was safe and increased the bed capacity at the two level three NICUs.

Caracterização do complexo Candida glabrata em isolados de hemocultura e avaliação da sensibilidade a antifúngicos / Characterization of the complex Candida glabrata in blood culture isolates and evaluation of sensitivity to antifungals

Candida glabrata assumiu grande importância na clínica médica, desde que, sua resistência adquirida ao fluconazol foi descrita. Além disso, estudos mostraram a fraca atividade in vitro de outros fármacos azólicos contra isolados dessa espécie. C. glabrata é agente de infecções invasivas e o monitoramento da eficácia de antifúngicos usados na prática médica frente a isolados dessa espécie tem relevância clinica. C. bracarensis e C. nivariensis são espécies relacionadas, fenotipicamente, à C. glabrata para as quais há necessidade de métodos moleculares para sua identificação. Na América Latina, a ocorrência de infecções em corrente sanguínea por C. glabrata e espécies correlatas não é tão alta quanto na América do Norte e, por isso, pouco é conhecido sobre sua distribuição e perfil de suscetibilidade a antifúngicos nessa região. Neste estudo, foram analisados 75 isolados com características morfológicas e bioquímicas de C. glabrata, obtidos da corrente sanguínea de pacientes atendidos em hospitais do estado de São Paulo, entre 2007 e 2013. As concentrações inibitórias mínimas (CIM) de cinco fármacos antifúngicos: anfotericina B, caspofungina, voriconazol, fluconazol e itraconazol, foram determinadas pela metodologia de microdiluição de referencia M27-A3 do Clinical and Laboratory Standards Institute (CLSI). A ação fungicida de anfotericina B foi avaliada por método de curva de morte. A pesquisa das duas espécies correlatas foi realizada com metodologia de reação em cadeia da polimerase (PCR) em todos os isolados. Nenhum isolado de C. bracarensis e C. nivariensis foi encontrado neste estudo. Resistência a itraconazol foi encontrada em 18,6 % (14) das cepas de C. glabrata. Altos valores de CIM de voriconazol (> 0,5 mg/L), de acordo com cutoff (ponto de corte) epidemiológico, foram observados para duas cepas...

Candida glabrata has assumed great importance in clinical medicine, since acquired resistance to fluconazole had been described. Furthermore, studies have shown the weak in vitro activity of other azole drugs against isolates of this species. Since C. glabrata is an agent of invasive infections, monitoring the effectiveness of antifungal agents used in medical practice against isolates of this species has become of great importance. C. bracarensis and C. nivariensis are phenotypically related species to C. glabrata and so it is necessary molecular methods to identify properly these members. In Latin America, the occurrence of bloodstream infections in C. glabrata and related species is not as high as in North America, and little is known about their distribution and antifungal susceptibility profile in this region. In this study, we analyzed 75 isolates with morphological and biochemical features of C. glabrata obtained from the bloodstream of patients treated in hospitals in the state of São Paulo, between 2007-2013. The minimum inhibitory concentrations (MIC) of five antifungal drugs, namely: amphotericin B, caspofungin, voriconazole, fluconazole and itraconazole were determined by microdilution reference method M27-A3 from the Clinical and Laboratory Standards Institute (CLSI). The fungicidal action of amphotericin B was evaluated by the method of time-kill curves. The investigation of the two related species was performed with polymerase chain reaction (PCR) in all isolates. No isolate of C. bracarensis and C. nivariensis was found in this study. Resistance to itraconazole was found in 18.6% (14) strains of C. glabrata. High MIC values of voriconazole (> 0.5 mg/L), according to epidemiological cut-off were observed for two strains. The fluconzole-MICs ranged from 4mg/L to 16mg/L, caspofungin-MIC were between 0.03 mg/L and 0.5 mg/L, and amphotericin B-MIC were between 0.12 mg/L and 1 mg/L...