Seven-day antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients: toward a new paradigm.

PURPOSE: Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14 days. METHODS: This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7 days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14 days of AT. RESULTS: Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9 days (IQR: 7-15) vs. 14 days (IQR: 13-22) (p = < 0.001). CONCLUSIONS: These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control.

Gross anatomy of the shoulder and arm intrinsic muscles in the white-footed tamarin (Saguinus leucopus - Günther, 1876): Inter- and intraspecific anatomical variations.

BACKGROUND: Saguinus leucopus is a Neotropical primate with an arboreal quadrupedal locomotion pattern, which requires wide movements of the shoulder and arm. This investigation studies the muscles of these regions in order to serve as a basis for clinical and surgical procedures and to compare with other primates. METHODS: Gross dissections of twenty thoracic limbs were performed. RESULTS: The muscles examined were the deltoid, supraspinatus, infraspinatus, subscapularis, teres major, teres minor, coracobrachialis longus, coracobrachialis brevis, biceps brachii, brachialis, triceps brachii, tensor fasciae antebrachii, and anconeus epitrochlearis. The anconeus was absent. The following variants were found: an accessory head of the biceps brachii, the unilateral absence of the short head of the biceps brachii, an accessory head of the coracobrachialis longus, and one infraspinatus muscle innervated by the axillary nerve. CONCLUSIONS: These muscles are adapted to quadrupedal locomotion and can have inter- and intraspecific variations in their attachments and innervation.

Morphometric, anatomic and radiographic study of the scapula in the white-footed tamarin (Saguinus leucopus): report of scapular cartilage and one variation in cranial (superior) transverse scapular ligament.

The white-footed tamarin (Saguinus leucopus) is an endangered endemic primate of Colombia, mainly due to the deforestation of its habitat and illegal trade, which generates a high incidence of these animals in wildlife care centres. Musculoskeletal system disorders in S. leucopus are one of the most common diseases and therefore the aim of this study was to contribute to the morphologic studies with a morphometric, anatomic and radiographic description of the scapula in this species to provide a basis for medical interventions, surgical approaches, radiologic diagnoses and comparative functions of this bone. Gross dissections of each scapular region were made in eight specimens without a diagnosis of osteomuscular disease. These specimens died from natural cases in the wildlife care centres of the Corporación Autónoma Regional de Caldas (CORPORCALDAS); after necropsy their carcasses were fixed with 10% formaldehyde, 5% mineral oil and 1% phenic acid in these centres over the course of at least 1 week. X-rays of the scapula were taken in the small animal clinic of the Universidad del Tolima, and morphometric data of the scapulae were obtained with a digital calliper. The scapula of the white-footed tamarin was a flat triangular bone with a deep scapular notch in its cranial margin, where there was a cranial transverse scapular ligament that was absent in two specimens. The coracoid process was highly developed, medially covering the humeral joint. The dorsal margin was covered by the scapular cartilage, which was highly developed in the caudal angle. In the dorsal fourth of the caudal margin, there was a surface from which the m. teres major originated. The lateral surface had a scapular spine with a long hamatus process of the acromion until the lateral part of the humeral joint. The infraspinatus fossa was wider than the supraspinous fossa. On the costal surface, the subscapular fossa was formed by three subscapular lines and one subscapular ridge, the latter helping to form the surface for the m. teres major. In the two radiographic views, caudocranial to the scapula and dorsoventral to the thorax, the scapular spine, acromion, coracoid process, scapular incisura, supraglenoid tubercle, caudal margin, subscapular ridge, and the joints with the clavicle and the humerus could be observed. The scapula of the white-footed tamarin presented bony reliefs that share characteristics with other primates but also with domestic mammals due to its quadrupedal locomotion, which allowed us to correlate its morphologic adaptation with its quadrupedal arboreal displacement.

Efficacy of ß-Lactam/ß-Lactamase Inhibitor Combinations for the Treatment of Bloodstream Infection Due to Extended-Spectrum-ß-Lactamase-Producing Enterobacteriaceae in Hematological Patients with Neutropenia.

ß-Lactam/ß-lactamase inhibitors (BLBLIs) were compared to carbapenems in two cohorts of hematological neutropenic patients with extended-spectrum-ß-lactamase (ESBL) bloodstream infection (BSI): the empirical therapy cohort (174 patients) and the definitive therapy cohort (251 patients). The 30-day case fatality rates and other secondary outcomes were similar in the two therapy groups of the two cohorts and also in the propensity-matched cohorts. BLBLIs might be carbapenem-sparing alternatives for the treatment of BSI due to ESBLs in these patients.

[Etiology and antimicrobial resistance of uncomplicated urinary tract infections]. / Etiología y resistencia a antimicrobianos de la infección no complicada del tracto urinario.

Uncomplicated urinary tract infections rank among the most frequent bacterial infections in women in the outpatient setting and represent a major cause of antimicrobial prescription. The aims of this study were to assess frequencies and antimicrobial resistance of current uropathogens causing uncomplicated urinary tract infection. In a prospective multicenter study, patients were recruited in ambulatory settings of four participating hospitals between June 2011 and December 2013. We analyzed 138 patients that met clinical and bacteriological diagnostic criteria. The mean age was 28 years. Cystitis was defined in 70% (n: 97) and pyelonephritis in 30% (n: 41). Frequencies of isolated microorganisms were: Escherichia coli 70% (n: 97), Staphylococcus saprophyticus 17% (n: 24), Proteus spp. 7% (n: 10), Klebsiella spp. 4% (n: 5), Enterococcus spp. and Pseudomonas aeruginosa 1 (0.7%) each. The antimicrobial resistance was: ampicillin-sulbactam 37% (n: 51) cephalexin 28% (n: 39), trimethoprim/sulfamethoxazole 22% (n: 31), nitrofurantoin 12% (n: 17), gentamicin 7% (n: 10) and ciprofloxacin 5% (n: 7). The levels of resistance found for ampicillin-sulbactam, trimethoprim/sulfamethoxazole and cephalexin were higher than those previously reported in Argentina. A better knowledge of the etiology and local antimicrobial susceptibility allows the design of more adequate guidelines for empirical treatment.

[Levofloxacin prophylaxis in neutropenic patients]. / Profilaxis con levofloxacina en pacientes neutropénicos.

Fluorquinolone-prophylaxis has proven useful in preventing infections in high risk neutropenic patients. The objective of this study was to describe the clinical, microbiological and therapeutic characteristics, and outcome of patients in the first episode of febrile neutropenia, comparing those who received levofloxacin prophylaxis with those who didn't. It was a prospective observational study that included all the episodes of inpatients with febrile neutropenia (February 1997- November 2014), also including the first episode in a same patient in different hospitalizations. Of 946 episodes here included, 821 presented high risk febrile neutropenia. A total of 264 cases (27.9%) received levofloxacin prophylaxis. This group consisted of a higher proportion of high risk febrile neutropenia (99.2% vs. 82.3%, p = 0.0001) and patients that had received an hematopoietic stem cell transplant (67.8% vs. 29.3%, p = 0.0001) compared to those who didn't receive prophylaxis. Those who received levofloxacin prophylaxis presented a similar frequency of clinically diagnosed but a lower proportion of microbiologically documented infections (28.8% vs. 37.5%, p = 0.012) than those who didn't receive prophylaxis. The episodes of bacteremia that occurred in the first group were more frequently caused by multidrug resistant bacteria (MDRB) (34.5% vs. 17.3%, p = 0.007) and by extended spectrum beta lactamase producing Enterobacteriaceae (19% vs. 3.8%, p = 0.0001). The group that received prophylaxis had a lower proportion of adequate empirical antibiotic treatment (69.7% vs. 83.7%, p = 0.009), with similar outcomes in both groups. We suggest that levofloxacin prophylaxis should be stopped whenever there is a rise in the frequency of MDRB infections in this population.

Letermovir Primary Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients: Real-Life Data from a University Hospital in Argentina.

Background: Cytomegalovirus (CMV) infection remains the most common clinically significant infection after allogeneic hematopoietic stem cell transplantation (allo-HCT) and is associated with considerable morbidity and mortality. Objectives: The present study was designed to describe and compare the incidence of untreated CMV reactivation (uCMVr), clinically significant infection (cs-CMVi) and disease (CMVd), as well as CMV-related hospitalization and outcome of allo-HCT patients, either treated with letermovir (LET) primary prophylaxis or managed with preemptive therapy (PET). Methods: This is a prospective observational cohort study of adult CMV seropositive allo-HCT patients who either received primary prophylaxis with LET within the first 100 days after HCT or were managed with PET. Results: The study population comprised 105 patients (28 in the LET group and 77 in the PET group). Compared to the PET group, patients in the LET group received more allo-HCT from alternative donors (54.5% vs. 82.14%, P=0.012). More than half of the patients in both groups were classified as high risk for CMVd. In the LET vs. PET group, cs-CMVi and CMVd developed respectively in 0 vs. 50 (64.94%), P=<0.0001, and 0 vs. 6 (7.79%), P=0.18. In the LET group, uCMVr occurred in 5 (17.8%) and were all considered blips. Hospital admissions related to cs-CMVi or CMVd in the PET group vs. LET group were 47 (61.04%) vs. 0, respectively, P=<0.0001. No differences were observed in 100-day mortality. Conclusions: LET primary prophylaxis proved effective in preventing cs-CMVi and CMVd and reducing hospitalizations in allo-HCT adults. Blips can occur during prophylaxis and do not require LET discontinuation.

Ceftazidime-Avibactam Improves Outcomes in High-Risk Neutropenic Patients with Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales Bacteremia.

Few studies have evaluated the efficacy of ceftazidime-avibactam (CA) for Klebsiella pneumoniae carbapenemase-producing Enterobacterales bacteremia (KPC-PEB) in high-risk neutropenic patients. This is a prospective multicenter observational study in high-risk neutropenic patients with multi-drug resistant Enterobacterales bacteremia. They were compared according to the resistance mechanism and definitive treatment provided: KPC-CPE treated with CA (G1), KPC-CPE treated with other antibiotics (G2), and patients with ESBL-producing Enterobacterales bacteremia who received appropriate definitive therapy (G3). Thirty-day mortality was evaluated using a logistic regression model, and survival was analyzed with Kaplan-Meier curves. A total of 238 patients were included: 18 (G1), 52 (G2), and 168 (G3). Klebsiella spp. (60.9%) and Escherichia coli (26.4%) were the Enterobacterales most frequently isolated, and 71% of the bacteremias had a clinical source. The resistance profile between G1 and G2 was colistin 35.3% vs. 36.5%, amikacin 16.7% vs. 40.4%, and tigeclycline 11.1% vs. 19.2%. The antibiotics prescribed in combination with G2 were carbapenems, colistin, amikacin, fosfomycin, tigecycline, and fluoroquinolones. Seven-day clinical response in G1 vs. G2 vs. G3 was 94.4% vs. 42.3% vs. 82.7%, respectively (p < 0.001). Thirty-day overall mortality in G1 vs. G2 vs. G3 was 22.2% vs. 53.8% vs. 11.9%, respectively (p < 0.001), and infection-related mortality was 5.5% vs. 51.9% vs. 7.7% (p < 0.001). The independent risk factors for mortality were Pitt score > 4: OR 3.63, 95% CI, 1.18-11.14 (p = 0.025) and KPC-PEB treated with other antibiotics: OR 8.85, 95% CI, 2.58-30.33 (p = 0.001), while 7-day clinical response was a protective factor for survival: OR 0.02, 95% CI, 0.01-0.08 (p < 0.001). High-risk neutropenic patients with KPC-CPE treated with CA had an outcome similar to those treated for ESBL-producing Enterobacterales, with higher 7-day clinical response and lower overall and infection-related mortality than those treated with other antibiotics. In view of these data, CA may be considered the preferred therapeutic option for KPC-PEB in high-risk neutropenic patients.

Pseudomonas aeruginosa Bloodstream Infections Presenting with Septic Shock in Neutropenic Cancer Patients: Impact of Empirical Antibiotic Therapy.

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.

Short Course of Antibiotic Therapy for Gram-Negative Bacilli Bacteremia in Patients with Cancer and Hematopoietic Stem Cell Transplantation: Less Is Possible.

Data about short courses of antibiotic therapy for Gram-negative bacilli (GNB) bacteremia in immunosuppressed patients are limited. This is a prospective observational study performed on adult patients with cancer and hematopoietic stem cell transplant (HSCT) who developed GNB bacteremia and received appropriate empirical antibiotic therapy (EAT), had a clinical response within 7 days and survived 48 h after the end of therapy. They received antibiotic therapy in the range of 7-15 days and were divided into short course, with a median of 7 days (SC), or long course, with a median of 14 days (LC). Seventy-four patients were included (SC: 36 and LC: 38). No differences were observed in baseline characteristics or in the presence of neutropenia: 58.3% vs. 60.5% (p = 0.84). Clinical presentation and microbiological characteristics were similar in SC and LC, respectively: clinical source of bacteremia 72.2% vs. 76.3% (p = 0.68); shock 2.8% vs. 10.5% (p = 0.35) and multidrug-resistant GNB 27.8% vs. 21.1% (p = 0.50). Overall, mortality was 2.8% vs. 7.9% (p = 0.61), and bacteremia relapse was 2.8% vs. 0 (p = 0.30). The length of hospitalization since bacteremia was 7 days (interquartile range (IQR), 6-15) for SC and 12 days (IQR, 7-19) (p = 0.021) for LC. In the case of patients with cancer or HSCT and GNB bacteremia who receive appropriate EAT with clinical response, 7 days of antibiotic therapy might be adequate.

Development of a Clinical Score to Stratify the Risk for Carbapenem-Resistant Enterobacterales Bacteremia in Patients with Cancer and Hematopoietic Stem Cell Transplantation.

Identifying the risk factors for carbapenem-resistant Enterobacterales (CRE) bacteremia in cancer and hematopoietic stem cell transplantation (HSCT) patients would allow earlier initiation of an appropriate empirical antibiotic treatment. This is a prospective multicenter observational study in patients from 12 centers in Argentina, who presented with cancer or hematopoietic stem-cell transplant and developed Enterobacterales bacteremia. A multiple logistic regression model identified risk factors for CRE bacteremia, and a score was developed according to the regression coefficient. This was validated by the bootstrap resampling technique. Four hundred and forty-three patients with Enterobacterales bacteremia were included: 59 with CRE and 384 with carbapenem-susceptible Enterobacterales (CSE). The risk factors that were identified and the points assigned to each of them were: ≥10 days of hospitalization until bacteremia: OR 4.03, 95% CI 1.88-8.66 (2 points); previous antibiotics > 7 days: OR 4.65, 95% CI 2.29-9.46 (2 points); current colonization with KPC-carbapenemase-producing Enterobacterales: 33.08, 95% CI 11.74-93.25 (5 points). With a cut-off of 7 points, a sensitivity of 35.59%, specificity of 98.43%, PPV of 77.7%, and NPV of 90.9% were obtained. The overall performance of the score was satisfactory (AUROC of 0.85, 95% CI 0.80-0.91). Finally, the post-test probability of CRE occurrence in patients with none of the risk factors was 1.9%, which would virtually rule out the presence of CRE bacteremia.

Outbreak of Klebsiella pneumoniae ST11 Resistant To Ceftazidime-Avibactam Producing KPC-31 and the Novel Variant KPC-115 during COVID-19 Pandemic in Argentina.

We describe an outbreak of Klebsiella pneumoniae sequence type 11 (ST11) producing KPC variants resistant to ceftazidime-avibactam. Six patients hospitalized in the intensive care unit (mostly due to critical COVID pneumonia) presented infection or colonization by this bacterium. They had several comorbidities and required mechanical ventilation, central venous catheters, and urinary catheters. All 6 patients had a history of fecal colonization with KPC-producing Enterobacterales (KPC-E). Three of them had previous episodes of infection with ceftazidime-avibactam-susceptible KPC-producing K. pneumoniae, which were treated with ceftazidime-avibactam. Several phenotypic methods failed to detect carbapenemase production in these 6 ceftazidime-avibactam-resistant isolates, and they showed in vitro susceptibility to imipenem and meropenem. All of them rendered positive results for blaKPC by PCR, and amplicon sequencing identified blaKPC-31 variant in 5 isolates and a novel variant, named blaKPC-115, in the other. Moreover, matrix-assisted laser desorption ionization-time of flight mass spectrometry was able to detect KPC in all isolates. Ceftazidime-avibactam-resistant isolates, as well as those recovered from previous infection episodes (KPC-3-producing K. pneumoniae, ceftazidime-avibactam susceptible), displayed a unique pulse type and belonged to ST11. Based on whole-genome sequencing results of selected isolates, less than 7 single-nucleotide polymorphisms were identified among them, which was indicative of the presence of a unique clone. Both in vivo selection and horizontal transmission seemed to have occurred in our hospital. Detection of these strains is challenging for the laboratory. History of previous KPC-E infections or colonization and systematic testing for resistance to ceftazidime-avibactam might help raise awareness of this possibility. IMPORTANCE Klebsiella pneumoniae is one of the main bacteria that cause infections in health care settings. This pathogen has developed a high level of resistance to many antibiotics. Some K. pneumoniae isolates can produce an enzyme known as carbapenemase KPC, making carbapenems (considered the last line for therapy) not effective to treat their infections. The combination ceftazidime-avibactam, approved by FDA in 2015, is useful to treat infections caused by KPC-producing K. pneumoniae. This study describes the emergence, in one hospital in Argentina, of K. pneumoniae isolates that produce KPC variants (KPC-31 and KPC-115) resistant to ceftazidime-avibactam. The ceftazidime-avibactam-resistant bacteria were isolated in inpatients, including some that previously received this combination as treatment. Transmission of this strain to other patients also occurred in the studied period. Detection of these bacteria is challenging for the laboratory. The knowledge and awareness of the emergence of this pathogen in our region are highly valuable.

Effect of Combination Antibiotic Empirical Therapy on Mortality in Neutropenic Cancer Patients with Pseudomonas aeruginosa Pneumonia.

To assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with Pseudomonas aeruginosa (PA) bacteremic pneumonia. This was a multinational, retrospective cohort study of neutropenic onco-hematological patients with PA bloodstream infection (BSI) (2006−2018). The effect of appropriate empirical combination therapy, appropriate monotherapy and inappropriate empirical antibiotic therapy [IEAT] on 30-day case-fatality was assessed only in patients with PA bacteremic pneumonia. Among 1017 PA BSI episodes, pneumonia was the source of BSI in 294 (28.9%). Among those, 52 (17.7%) were caused by a multidrug-resistant (MDR) strain and 68 (23.1%) received IEAT, mainly when the infection was caused by an MDR strain [38/52 (73.1%) vs. 30/242 (12.4%); p < 0.001]. The 30-day case-fatality rate was higher in patients with PA bacteremic pneumonia than in those with PA BSI from other sources (55.1% vs. 31.4%; p < 0.001). IEAT was associated with increased 30-day case-fatality (aHR 1.44 [95%CI 1.01−2.03]; p = 0.042), whereas the use of appropriate combination empirical treatment was independently associated with improved survival (aHR 0.46 [95%CI 0.27−0.78]; p = 0.004). Appropriate empirical monotherapy was not associated with improved overall survival (aHR 1.25 [95%CI 0.76−2.05]; p = 0.39). Combination antibiotic empirical therapy should be administered promptly in febrile neutropenic patients with suspected pneumonia as the source of infection.

Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors.

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006−May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.

Healthcare personnel infected with novel influenza A H1N1 virus in university hospitals in Buenos Aires, Argentina.

Data on the clinical presentation, risk factors, and outcomes for healthcare personnel (HCP) infected with influenza A H1N1 virus (H1N1) are limited. From June to July 2009, a prospective study was conducted among HCP with influenza-like illness (ILI) at university hospitals in Buenos Aires. A reverse transcription polymerase chain reaction (RT-PCR) was used to diagnose H1N1. A logistic regression model was developed to identify factors associated with H1N1. Among 1519 HCP, 96 (6.3%) were diagnosed with an ILI. Of these, 85 (88.5%) were swabbed for H1N1 detection, with 43 positive cases (2.8%). Seasonal influenza immunization was recorded in 76%. Comparison of H1N1-positive vs. H1N1-negative cases showed that H1N1-positive cases more frequently had asthenia (72% vs. 48%, p = 0.03) and cough (79% vs. 43%, p = 0.008) and less frequently had diarrhoea (9% vs. 29%, p = 0.03) and prior prophylaxis with oseltamivir (5% vs. 31%, p = 0.002). The logistic regression model showed that presence of cough (odds ratio (OR) 6.93, 95% confidence interval (CI) 2.24, 21.4) was associated with an increased risk of H1N1. Prior prophylaxis with oseltamivir (OR 0.08, 95% CI 0.01, 0.43) was associated with a lower probability of H1N1 infection. A high proportion of HCP with an ILI were infected with H1N1. Complication rates were relatively low. Prior prophylaxis with oseltamivir was associated with a lower risk of developing H1N1.

[Primary antifungal prophylaxis in oncohematological patients: who, when, and with what?] / Profilaxis antifúngica primaria en pacientes oncohematológicos: ¿a quiénes, cuándo y con qué?

Invasive fungal infections (IFI) are among the main infectious complications in patients with hematological malignancies and with hematopoietic stem cell transplant (HSCT), causing high morbidity and mortality and significantly increasing the healthcare cost and hospital stay. The epidemiology of IFIs has changed in recent decades, with filamentous fungi, particularly Aspergillus spp., being the main etiological agents. There are multiple risk factors for having an IFI; however, the most important are profound and prolonged neutropenia and severe cellular immunodeficiency. For this reason, the population at greatest risk is made up of patients with acute leukemias, myelodysplasias and allogeneic HSCT with graft-versus-host disease (GVHD) treated with corticosteroids. Numerous randomized clinical trials and meta-analyses have shown that primary antifungal prophylaxis (AFP) significantly reduces the incidence of IFI, particularly those caused by Candida spp. and Aspergillus spp., IFI-related mortality, and overall mortality in some group of patients. Likewise, in high-risk patients, where a high incidence of IFI is expected, it is a cost-effective strategy. Several antifungals have demonstrated clinical benefit. They can be used as a AFP strategy in different settings, presenting advantages and disadvantages that must be taken into account in each case. For this, national and international scientific societies have issued recommendations for the indication of AFP. Aspects related to the different antifungals' clinical efficacy are analyzed considering the population at risk, the potential disadvantages, timing, and form of administration.

Las infecciones fúngicas invasoras (IFI) constituyen una de las principales complicaciones infecciosas en pacientes oncohematológicos y con trasplante de células progenitoras hematopoyéticas (TCPH), ocasionando alta morbimortalidad e incrementando significativamente los costos de atención y la estadía hospitalaria. La epidemiología de las IFI ha cambiado en las últimas décadas, siendo los hongos filamentosos, particularmente Aspergillus spp., los principales agentes etiológicos. Existen múltiples factores de riesgo para una IFI; pero la neutropenia profunda y prolongada, y la inmunodeficiencia celular severa siguen siendo los más importantes. Por este motivo, la población de mayor riesgo la constituyen los pacientes con leucemias agudas, mielodisplasias y TCPH alogénicos con enfermedad injerto contra huésped (EICH), en tratamiento con corticoides. Numerosos ensayos clínicos aleatorizados y metaanálisis han demostrado que la profilaxis antifúngica primaria (PAF) reduce significativamente la incidencia de IFI, tanto de aquellas causadas por Candida spp. como por Aspergillus spp., la mortalidad relacionada a IFI y la mortalidad global en algunos grupos de pacientes. Asimismo, en enfermos de alto riesgo, en donde se espera una incidencia de IFI elevada, es una estrategia costo-efectiva. Varios antifúngicos han demostrado beneficio clínico y pueden utilizarse como estrategia de PAF en diferentes escenarios, presentando ventajas y desventajas que deben ser tenidas en cuenta al momento de indicar una PAF. Para esto, sociedades científicas nacionales e internacionales, han emitido recomendaciones de indicación de PAF. Se analizan los aspectos relacionados con la eficacia clínica de los diferentes antifúngicos según la población de riesgo, las potenciales desventajas, momento y forma de administración.

[SARS-COV-2 infection in patients with hematological malignancies and transplants]. / Infección por SARS-CoV-2 en pacientes con neoplasias hematológicas y trasplantes.

SARS-CoV-2 infection in patients with hematological malignancies and hematopoietic stem cell transplants (HSCT) can be severe and with significant mortality. We carried out a prospective and observational study to describe the clinical and epidemiological characteristics and outcome of SARS-CoV-2 infection in patients with hematological malignancies and HSCT. Twenty adult patients were included with a median age of 58 years and a median Charlson score of 3. Infections were community-acquired and nosocomial in 60% and 40%, respectively, and 30% of the patients had a history of contact with a SARS-CoV-2 infected person. Sixty-five percent had pulmonary infiltrates, mostly with a ground-glass pattern on CT scan. Almost half of the patients had a severe and critical illness, and a high proportion received convalescent plasma as treatment. Twenty percent and 15% had complications and hospital infections, respectively, and had prolonged hospitalization expressed as median days of it. The 30-day mortality was 10%. SARS-CoV-2 infection in our population had a considerable clinical and epidemiological impact.

La infección por SARS-CoV-2 en pacientes con neoplasias hematológicas y trasplantes de células progenitoras hematopoyéticas (TCPH) puede ser grave y con importante mortalidad. Llevamos a cabo un estudio prospectivo y observacional que tuvo como objetivo describir las características clínicas, epidemiológicas y la evolución de la infección por SARS-CoV-2 en pacientes con neoplasias hematológicas y TCPH. Se incluyeron 20 pacientes adultos con una mediana de edad de 58 años y una mediana de score de Charlson de 3. Las infecciones fueron de adquisición comunitaria y nosocomial en el 60% y 40% respectivamente, y el 30% de los pacientes tenía antecedente de contacto con una persona infectada por SARS-CoV-2. El 65% presentó infiltrados pulmonares, mayormente con patrón de vidrio esmerilado en la tomografía computarizada de tórax. Casi la mitad de los pacientes tuvo enfermedad grave y crítica, y una alta proporción recibió plasma de convalecientes como tratamiento. Presentaron complicaciones e infecciones hospitalarias el 20% y 15% respectivamente, y tuvieron una mediana de días de internación prolongada. La mortalidad a 30 días fue del 10%. La infección por SARS-CoV-2 en nuestra población tuvo considerable impacto clínico y epidemiológico.

[Incidence, clinical characteristic and evolution of Clostridioides difficile infection]. / Incidencia, características clínicas y evolución de la infección por Clostridioides difficile.

Clostridioides difficile infection (CDi) is one of the foremost hospital-acquired infections. We present an observational study aimed to describe the incidence, epidemiology, and clinical outcome of CDi in a tertiary university hospital in Buenos Aires. The episodes, diagnosed in 117 consecutive adult patients in the period 01/01/2017 to 01/04/2020, were distributed in three groups: 63 (53.9%) were classified as hospital-acquired infections (HA), 25 (21.4%) as community onset-health care-associated infections (CO-HCA) and 29 (24.8%) as community-associated infections (CA). The incidence of HA CDi infections was 3.1, 5. 2 and 2.8 every 10 000 patient days in 2017, 2018 and 2019, respectively. The microbiological diagnosis was made by immunochromatography with antigen GDH and C. difficile toxin positive in 51 episodes (43.6%) and by GDH positive, toxin negative and PCR positive in 66 episodes (56.4%). Older age (p = 0.018), chronic kidney disease (p = 0.013), immunosuppression (p = 0.021), and higher comorbidity Charlson score (p = 0.001) were observed in patients with IH and CA-HCA infections. No significant differences in clinical features were found among groups. During the hospital st ay, 13 patients (11.1%) required admission to the intensive care unit. Ten recurrences occurred, representing 8.5% of CDI episodes. The 90-day mortality was 19.8%, being significantly higher in HA and CO-HCA infections (p = 0.014). Our findings highlight both the local burden of CDi morbidity and mortality and the need for the implementation of preventive strategies.

La infección por Clostridioides difficile (ICD) es una de las más importantes infecciones intrahospitalarias. Se realizó un estudio observacional que describe la incidencia, las características epidemiológicas y la evolución clínica de la ICD en un hospital universitario de la Ciudad de Buenos Aires. Los episodios, diagnosticados en 117 pacientes adultos consecutivos entre el 01/01/2017 y el 01/04/2020, fueron clasificados en ICD intrahospitalaria (IH) en 63 (53.9%), de inicio comunitario y asociada al ámbito de la salud (ICAAS) en 25 (21.4%) y comunitaria (CO) en 29 (24.8%) pacientes. La incidencia de ICD IH fue 3.1, 5.2 y 2.8 cada 10 000 días paciente en 2017, 2018 y 2019, respectivamente. El diagnóstico microbiológico se realizó mediante inmunocromatografía con glutamato deshidrogenasa y toxina positivas en 51 (43.6%) y mediante glutamato deshidrogenasa positiva, toxina negativa y PCR positiva en 66 (56.4%). Los pacientes con ICD IH e ICAAS presentaron mayor edad (p = 0.018), mayor frecuencia de insuficiencia renal crónica (p = 0.013) e inmunosupresión (p = 0.021) y mayor puntaje en índice Charlson de comorbilidad (p = 0.001). No hubo diferencia significativa en la forma de presentación clínica entre los tres grupos. Durante la evolución de la ICD, 13 (11.1%) pacientes requirieron internación en terapia intensiva. Se registraron 10 recurrencias, que correspondieron al 8.5% de los episodios de ICD. La mortalidad a los 90 días fue 19.8%, significativamente mayor en los pacientes con ICD IH e ICAAS (p = 0.014). Estos hallazgos destacan la considerable carga de morbilidad de la ICD y la necesidad de implementar estrategias preventivas.

Clinical Usefulness of Bronchoalveolar Lavage in the Management of Pulmonary Infiltrates in Adults with Hematological Malignancies and Stem Cell Transplantation.

INTRODUCTION: Pulmonary complications are frequent in patients with hematologic malignancies and stem cell transplantation. Regardless of the microbiological usefulness of bronchoalveolar lavage (BAL), little information exists on both its benefits as a guide for therapeutic decisions and its impact on patients' clinical outcome. METHODS: A prospective observational single-center study was performed between July 2011 and July 2016. Consecutive episodes of pulmonary infiltrates were analyzed in subjects over 18 years of age who presented hematologic malignancies and underwent chemotherapy or stem cell transplantation. RESULTS: Ninety-six episodes of pulmonary infiltrates were analyzed. Acute leukemia was the most frequent underlying condition. Thirty-seven patients (38.5%) received a stem cell transplant. Sixty-one (62.9%) were neutropenic at the moment of inclusion in the study. A definitive etiologic diagnosis was obtained in 41 cases (42.7%), where infection accounted for the vast majority of cases (33 cases, 80.5%). Definitive diagnosis was reached by non-invasive methods in 13 cases (13.5%). BAL was performed in 47 cases and led to a diagnosis in 40.4% of the cases. BAL results led to therapeutic changes in 27 cases (57.4%), including the addition of new antimicrobials to empiric treatments in 10. Regarding BAL's safety, two patients experienced minor adverse events and one a severe adverse event; no procedure-related deaths were observed. CONCLUSIONS: Infection was the leading cause of pulmonary infiltrates in patients with hematologic malignancies and stem cell transplantation. BAL was a useful decision-making diagnostic tool, with minor adverse events.

Proposal of a clinical score to stratify the risk of multidrug-resistant gram-negative rods bacteremia in cancer patients.

INTRODUCTION: Multidrug-resistant gram-negative rods (MDR GNR) represent a growing threat for patients with cancer. Our objective was to determine the characteristics of and risk factors for MDR GNR bacteremia in patients with cancer and to develop a clinical score to predict MDR GNR bacteremia. MATERIAL AND METHODS: Multicenter prospective study analyzing initial episodes of MDR GNR bacteremia. Risk factors were evaluated using a multiple logistic regression (forward-stepwise selection) analysis including variables with a p<0.10 in univariate analysis. RESULTS: 394 episodes of GNR bacteremia were included, with 168 (42.6 %) being MDR GNR. Five variables were identified as independent risk factors: recent antibiotic use (OR=2.8, 95 % CI 1.7-4.6, p=0.001), recent intensive care unit admission (OR=2.9, 95 % CI 1.1-7.8, p=0.027), hospitalization ≥ 7 days prior to the episode of bacteremia (OR=3.5, 95 % CI 2-6.2, p=0.005), severe mucositis (OR=5.3, 95 % CI 1.8-15.6, p=0.002), and recent or previous colonization/infection with MDR GNR (OR=2.3, 95 % CI 1.2-4.3, p=0.028). Using a cut-off value of two points, the score had a sensitivity of 66.07 % (95 % CI 58.4-73.2 %), a specificity of 77.8 % (95 % CI 71.4-82.7 %), a positive predictive value of 68 % (95 % CI 61.9-73.4 %), and a negative predictive value of 75.9 % (95 % CI 71.6-79.7 %). The overall performance of the score was satisfactory (AUROC 0.78; 95 % CI 0.73-0.82). In the cases with one or none of the risk factors identified, the negative likelihood ratio was 0.18 and the post-test probability of having MDR GNR was 11.68 %. CONCLUSIONS: With the growing incidence of MDR GNR as etiologic agents of bacteremia in cancer patients, the development of this score could be a potential tool for clinicians.