Tranexamic acid in cardiac surgery: Are low doses enough?

OBJECTIVES: Tranexamic acid is used to prevent hyperfibrinolysis and reduce postoperative bleeding and blood transfusions in on-pump cardiac surgery. We evaluate the efficacy of low or high dose tranexamic acid in a prospective cohort study conducted in Valencia. MATERIALS AND METHODS: A total of 427 patients were recruited between January 2019 and January 2020, 207 in the Hospital General Universitario (low dose [LD]) and 220 in the Hospital Universitario y Politécnico La Fe (high dose [HD] and intermediate dose [ID]). We recorded the presence of hyperfibrinolysis on rotational thromboelastometry, intra- and postoperative administration of blood products, chest tube output within the first 12 h, and incidence of convulsions. Univariate and multivariate comparisons were performed. Univariate analysis of all categories was performed after propensity score matching between LD and HD and between LD and ID. RESULTS: There were no statistically significant differences in: appearance of hyperfibrinolysis, administration of blood products, postoperative chest tube output within the first 12 h, or occurrence of convulsions. Group LD received less fibrinogen than group HD (P = .014) and ID (P = .040) but more fresh frozen plasma than group ID (P = .0002). CONCLUSIONS: Administration of low-dose tranexamic acid is as effective as higher doses in hyperfibrinolysis prophylaxis and the prevention of postoperative bleeding in cardiac surgery.

Tranexamic acid in cardiac surgery: Are low doses enough? / Ácido tranexámico en cirugía cardíaca: ¿las dosis bajas son suficientes?

OBJECTIVES: Tranexamic acid is used to prevent hyperfibrinolysis and reduce postoperative bleeding and blood transfusions in on-pump cardiac surgery. We evaluate the efficacy of low or high dose tranexamic acid in a prospective cohort study conducted in Valencia. MATERIALS AND METHODS: A total of 427 patients were recruited between January 2019 and January 2020, 207 in the Hospital General Universitario (low dose [LD]) and 220 in the Hospital Universitario y Politécnico La Fe (high dose [HD] and intermediate dose [ID]). We recorded the presence of hyperfibrinolysis on rotational thromboelastometry, intra- and postoperative administration of blood products, chest tube output within the first 12h, and incidence of convulsions. Univariate and multivariate comparisons were performed. Univariate analysis of all categories was performed after propensity score matching between LD and HD and between LD and ID. RESULTS: There were no statistically significant differences in: appearance of hyperfibrinolysis, administration of blood products, postoperative chest tube output within the first 12h, or occurrence of convulsions. Group LD received less fibrinogen than group HD (P=.014) and ID (P=.040) but more fresh frozen plasma than group ID (P=.0002). CONCLUSIONS: Administration of low-dose tranexamic acid is as effective as higher doses in hyperfibrinolysis prophylaxis and the prevention of postoperative bleeding in cardiac surgery.

Efficacy of Lysophosphatidylcholine in Combination with Antimicrobial Agents against Acinetobacter baumannii in Experimental Murine Peritoneal Sepsis and Pneumonia Models.

Immune response stimulation to prevent infection progression may be an adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC) is an immunomodulator involved in immune cell recruitment and activation. In this study, we aimed to evaluate the efficacy of LPC in combination with colistin, tigecycline, or imipenem in experimental murine models of peritoneal sepsis and pneumonia. We used Acinetobacter baumannii strain Ab9, which is susceptible to colistin, tigecycline, and imipenem, and multidrug-resistant strain Ab186, which is susceptible to colistin and resistant to tigecycline and imipenem. Pharmacokinetic and pharmacodynamic parameters for colistin, tigecycline, and imipenem and the 100% minimal lethal dose (MLD100) were determined for both strains. The therapeutic efficacies of LPC, colistin (60 mg/kg of body weight/day), tigecycline (10 mg/kg/day), and imipenem (180 mg/kg/day), alone or in combination, were assessed against Ab9 and Ab186 at the MLD100 in murine peritoneal sepsis and pneumonia models. The levels of pro- and anti-inflammatory cytokines, i.e., tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay (ELISA) for the same experimental models after inoculating mice with the MLD of both strains. LPC in combination with colistin, tigecycline, or imipenem markedly enhanced the bacterial clearance of Ab9 and Ab186 from the spleen and lungs and reduced bacteremia and mouse mortality rates (P < 0.05) compared with those for colistin, tigecycline, and imipenem monotherapies. Moreover, at 4 h post-bacterial infection, Ab9 induced higher TNF-α and lower IL-10 levels than those with Ab186 (4 µg/ml versus 3 µg/ml [P < 0.05] and 2 µg/ml versus 3.4 µg/ml [P < 0.05], respectively). LPC treatment combined with colistin, tigecycline, or imipenem modestly reduced the severity of infection by A. baumannii strains with different resistance phenotypes compared to LPC monotherapy in both experimental models.

Clinical and molecular epidemiology of meticillin-resistant Staphylococcus aureus causing bacteraemia in Southern Spain.

BACKGROUND: Some molecular features of meticillin-resistant Staphylococcus aureus (MRSA) isolates causing invasive infections have been shown to have clinical implications. There is a need to monitor the situation using a combination of molecular and clinical data because, although MRSA clones tend to predominate over wide geographical areas, clonal shifts may take place. AIM: To study the epidemiological features and perform molecular characterization of a retrospective cohort of 98 cases of nosocomial and healthcare-associated MRSA bacteraemia in 10 hospitals in Andalusia, Spain. METHODS: Relatedness of isolates was investigated using pulsed-field gel electrophoresis (PFGE), S. aureus protein A (spa) typing and clonal complex (CC) assignment. Staphylococcal chromosomal cassette mec (SCCmec) type and accessory gene regulator (agr) group were studied by polymerase chain reaction. agr function was assessed. RESULTS: Most isolates were CC5, SCCmec type IV and agr group II. The most common spa type was t067. Six major clusters were identified by PFGE. Six small clusters of epidemiologically related cases sharing isolates from the same PFGE subtype were identified. Five percent of isolates had a vancomycin minimum inhibitory concentration (MIC) of 2 µg/mL on broth microdilution, although 44% had an MIC >1 µg/mL on E-test. Variables independently associated with MIC >1 mg/L on E-test were surgery during present admission and Charlson index ≥2. CONCLUSION: A specific CC that has been predominant in Spain over the last decade caused most of the cases in this study. PFGE was more discriminatory than spa typing in showing clusters of epidemiologically related cases. Some patient features were associated with vancomycin MIC >1 mg/L on E-test.

In vitro and in vivo reduced fitness and virulence in ciprofloxacin-resistant Acinetobacter baumannii.

Limited data on relative fitness and virulence of antimicrobial-resistant Acinetobacter baumannii are known. We aimed to study the virulence and fitness cost of ciprofloxacin-resistance in A. baumannii (CipR) compared with the susceptible parental wild-type strain (CipS). Human lung epithelial cells were infected with CipS and CipR for 24 h. Competition fitness was monitored in vitro and in vivo in a murine peritoneal sepsis model. We showed that CipR induced less cell death than CipS and CipR growth was slow when in competition with CipS. Altogether, acquisition of ciprofloxacin resistance confers a biological fitness cost and reduces virulence in A. baumannii.

In vitro activity of several antimicrobial peptides against colistin-susceptible and colistin-resistant Acinetobacter baumannii.

At present, colistin is among the few antibiotics effective against Acinetobacter baumannii clinical isolates. However, in the last few years, colistin-resistant A. baumannii strains have been isolated. Therefore, antibiotics effective against these usually pan-resistant colistin-resistant A. baumannii strains are required. The main objective of this study was to analyse the activity of 15 peptides against colistin-susceptible and colistin-resistant A. baumannii. The MICs were determined by microdilution. Among these 15 antimicrobial peptides (AMPs), melittin, indolicidin and mastoparan showed good activity against both colistin-susceptible and colistin-resistant A. baumannii. Further studies of mastoparan with time-killing curves showed bactericidal activity at MIC ×8 for both colistin-susceptible and colistin-resistant A. baumannii. In conclusion, mastoparan may be a potential alternative for the treatment of colistin-resistant A. baumannii infections.

Immunosuppressed patients with pandemic influenza A 2009 (H1N1) virus infection.

The purpose of this paper was to prospectively characterize the clinical manifestations and outcomes of confirmed influenza A 2009 (H1N1) virus infection in immunosuppressed patients with hospital admission and compare them with those of a general population. A multicenter prospective cohort study was carried out. All adult patients admitted to 13 hospitals in Spain with confirmed influenza A 2009 (H1N1) virus infection from June 12, 2009 to November 11, 2009 were included. Risk factors for complicated influenza infection were studied in immunosuppressed patients. Overall, 559 patients were included, of which 56 were immunosuppressed, nine with solid or hematological malignancies, 18 with solid-organ transplant recipients, 13 with corticosteroid therapy, and six with other types of immunosuppression. Clinical findings at diagnosis were similar in both groups. Nineteen immunosuppressed patients had pneumonia (33.9%). Immunosuppressed patients with pandemic influenza had bacterial co-infection more frequently (17.9% vs. 6.4%, p = 0.02), specifically, gram-negative bacilli and Staphylococcus aureus infections. Mortality was higher in immunosuppressed patients (7.1% vs. 1.8%, p < 0.05). The only modifiable risk factor of complicated influenza A 2009 (H1N1) was delayed antiviral therapy. In immunosuppressed patients, influenza A 2009 (H1N1) virus infection has higher mortality than in non-immunosuppressed individuals. Bacterial co-infection is common in complicated cases.

Empirical antifungal therapy in selected patients with persistent febrile neutropenia.

Universal empirical antifungal therapy (EAT) in patients with unexplained persistent febrile neutropenia (PFN) is the standard of care, but EAT could be applied in selected patients on the basis of clinical criteria and risk factors. A prospective interventional study was carried out to analyse the incidence and related mortality of invasive fungal infection (IFI) in patients with PFN according to whether or not EAT was indicated. EAT was indicated according to the following criteria: (a) severe sepsis or septic shock; (b) focused infection: lung, central nervous system, sinus, abdominal or skin; (c) individualized clinical decision in patients at high risk. Sixty-six (19%) of 347 episodes of febrile neutropenia fulfilled PFN criteria, 97% with a haematological malignancy. Just 26 (39.4%) were treated with EAT. The overall IFI incidence was 4.5%. In the group that received EAT, three patients developed IFI (11.5%), in comparison with none in the group that did not receive it (P=0.04, RR 2.7:1.9-3.8). IFI-related mortality was null in the group that did not receive EAT and 8% (two of 26 patients) in the group that received EAT. These data suggest that in patients with PFN, EAT in selected patients may be safe and avoid unnecessary antifungal therapy.

Risk-factors for the acquisition of imipenem-resistant Acinetobacter baumannii in Spain: a nationwide study.

Potential risk-factors for the acquisition of imipenem-resistant Acinetobacter baumannii were investigated in a cohort study in 25 Spanish hospitals. The clonal relationship among isolates was determined by pulsed-field gel electrophoresis (PFGE). In total, A. baumannii was isolated from 203 patients, with imipenem-resistant (MIC(90) 128 mg/L) isolates being obtained from 88 patients (43%), and imipenem-susceptible isolates from 115 patients (57%). A wide clonal distribution was observed among the imipenem-resistant isolates, but spread of the same clone among centres was not demonstrated. The results indicated that imipenem-resistant A. baumannii is a widely distributed nosocomial pathogen in Spain and reaches an alarming frequency in some centres. Independent risk-factors for the acquisition of imipenem-resistant A. baumannii were a hospital size of >500 beds (multivariate OR, 6.5; 95% CI, 1.8--23), previous antimicrobial treatment (multivariate OR, 4.3; 95% CI, 1.6--11), a urinary catheter (multivariate OR, 2.7; 95% CI, 1.1--6.7) and surgery (multivariate OR, 2; 95% CI, 1.07--3.8).

Tuberculous vertebral osteomyelitis in the new millennium: still a diagnostic and therapeutic challenge.

In order to determine the clinical features and current prognosis of tuberculous vertebral osteomyelitis, the charts of all patients diagnosed with definite or probable tuberculous vertebral osteomyelitis from January 1983 to June 2002 ( n=78) were reviewed. The mean delay to diagnosis was 6.1 months. Sixty-five (83.3%) patients had inflammatory spinal pain, 35 (44.9%) had some neurological deficit, and only 27 (34.6%) had fever. Paravertebral, epidural, and psoas abscesses were detected in 73.1, 65.4, and 24.4% of the cases, respectively. Culture was positive in 48% of the percutaneous biopsies and in 61.7% of the open biopsies. After histological findings were included, the diagnostic yield of percutaneous biopsies was 68%. Fifty-five (70.5%) patients required surgical treatment at some stage of the disease. Although no deaths were directly attributable to tuberculous vertebral osteomyelitis and only 5.1% of patients relapsed, the mean overall hospital stay was 69.1+/-36.9 days, and 30 (38.5%) patients had severe functional sequelae. In conclusion, diagnosis of tuberculous vertebral osteomyelitis requires a high degree of suspicion. Percutaneous biopsy should be undertaken as soon as possible in any patient with compatible symptoms or radiological images in order to initiate suitable therapy.

Brucella endocarditis: clinical, diagnostic, and therapeutic approach.

Brucella endocarditis is an uncommon focal complication of brucellosis. Presented here are 11 cases of Brucella endocarditis, all managed uniformly. The median duration of symptoms prior to diagnosis was 3 months. Five patients (45%) had underlying valvular damage, and in six (55%) endocarditis involved a normal valve. There was a predominance of aortic involvement (82%) and a high incidence of left ventricular failure (91%). Diagnostic suspicion was essential in order to test blood cultures correctly, which in this series were positive in 63% of the patients. Surgical treatment was undertaken in eight patients (72%), all with aortic involvement and left ventricular failure impossible to control with medication. One patient died during the immediate postoperative period. All the other patients received antibiotic therapy for 3 months, with no signs of relapse of the infection or malfunction of the prosthesis during a minimum follow-up period of 24 months.

Orbital hydatid cyst: treatment and prevention of recurrences with albendazole plus praziquantel.

A case of successful treatment of orbital echinococcosis without evidence of recurrence on prolonged follow-up is presented. The management of orbital hydatid cyst is discussed. ¿ 2000 The British Infection Society

Cerebrospinal fluid tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-8 as diagnostic markers of cerebrospinal fluid infection in neurosurgical patients.

OBJECTIVE: To evaluate whether cerebrospinal fluid concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, or IL-8 may be used as diagnostic markers for the differential diagnosis of aseptic vs. bacterial meningitis and/or ventriculitis in neurosurgical patients. DESIGN: Prospective, observational study. SETTING: University teaching hospital. SUBJECTS: A total of 112 cerebrospinal fluid samples from 14 asymptomatic patients with normal cerebrospinal fluid after neurosurgery, 27 asymptomatic and 19 symptomatic patients with postneurosurgical aseptic meningitis, 32 patients with postneurosurgical cerebrospinal fluid infection, and 20 with severe subarachnoid and/or cerebral hemorrhage. MEASUREMENTS AND MAIN RESULTS: Specific ELISA kits were used to analyze TNF-alpha, IL-1beta, IL-6, and IL-8 concentrations on cerebrospinal fluid samples. Elevations in cerebrospinal fluid concentrations of TNF-alpha, IL-1beta, IL-6, and IL-8 were induced by different diseases or neurosurgical procedures, but cerebrospinal fluid bacterial infection induced the highest concentrations. To discriminate between aseptic cerebrospinal fluid pleocytosis and cerebrospinal fluid infection with a specificity of 95%, cerebrospinal fluid leukocyte count >1700/mL, TNF-alpha >150 pg/mL, and IL-1beta >90 pg/mL showed sensitivities of 51%, 74%, and 90%, respectively. Sufficiently sensitive and specific cutoff points could not be found for cerebrospinal fluid IL-6 or IL-8. CONCLUSION: Cerebrospinal fluid IL-1beta appears to be the best biochemical marker of cerebrospinal fluid infection in neurosurgical patients.

Postoperative spondylodiskitis: etiology, clinical findings, prognosis, and comparison with nonoperative pyogenic spondylodiskitis.

We studied 31 cases of postoperative pyogenic spondylodiskitis (POS), comparing them with 72 cases of nonpostoperative pyogenic spondylodiskitis (NPOS). POS represents 30.1% of cases of pyogenic spondylodiskitis. The onset of symptoms occurred an average (+/-SD) of 27.7 (+/- 25.3) days following surgery. Predisposing factors were less frequent in POS than NPOS cases (P = .002). Neurological complications and inflammatory signs in the spine were more frequent with POS than with NPOS (P = .002 and P < .00001). Coagulase-negative Staphylococcus and anaerobic bacteria were more frequent in POS than in NPOS (P = .0001 and P = .05). Percutaneous bone biopsies yielded the etiology in 66.7% of cases, open bone biopsies in 100%, blood cultures in 55.6%, and cultures of adjacent foci in 94.4%. Eleven patients (35.5%) were cured with antimicrobial treatment, but surgical treatment was necessary in 64.5%. No relapses or deaths were recorded. Seventeen patients (54.8%) had severe functional sequelae, which were associated with inflammatory signs in the spine (P = .033), higher levels of leukocytosis (P = .05), higher erythrocyte sedimentation rates (P = .05), and paravertebral abscesses (P = .04).

Etiology, clinical features and outcome of splenic microabscesses in HIV-infected patients with prolonged fever.

A prospective study was conducted to determine the etiology, clinical features, and outcome in a series of 32 consecutively enrolled HIV-infected patients with prolonged fever in whom high resolution (7.5 Mhz) sonography revealed multiple splenic microabscesses. Conventional (3.5 Mhz) sonography showed no splenic abnormalities in any patients. The diagnoses were: tuberculosis (14), visceral leishmaniasis (7), disseminated Mycobacterium avium complex infection (5), Salmonella spp. bacteremia (2), lymphoma (2), disseminated Rhodococcus equi infection (1), disseminated Candida krusei infection (1) and Pneumocystis carinii pneumonia (1). Twenty-eight patients were followed up for six months and four were lost to follow-up. In 16 patients with a clinical cure and microbiological eradication, the findings on follow-up high resolution sonography were normal, and in two patients the microabscesses persisted; ten patients died. In conclusion, the findings suggest splenic microabscesses may be a frequent condition in HIV-infected patients with prolonged fever, being an unspecific manifestation of the opportunistic diseases causing fever of unknown origin in this population. They cannot be detected by conventional abdominal sonography, whereas high resolution sonography is a useful technique for their detection and follow-up.

Efeito do esteróide nos limiares agudos de um eletrodo atrial e ventricular de fixaçäo ativa / Steroid effect of an active fixation lead on acute atrial and ventricular pacing thresholds

OBJETIVO: Comparar a performance de um eletrodo bipolar permanente com fixaçäo ativa e colar de esteróides, com outro eletrodo semelhante, mas sem o colar de esteróide. MATERIAL E MÉTODO: Este estudo foi realizado em 2 fases em 3 centros no Brasil: na fase atrial eletrodos Sweet Tip Rx e Sweet Tip foram implantados em 16 e 8 pacientes, respectivamente. Em todos os pacientes os limiares de voltagem (largura de pulso = 0,5ms) e a largura de pulso (amplitude = 1,5V) foram medidos por ocasiäo da alta hospitalar, 2 semanas e 3 ou 4 meses após o implante. RESULTADOS: Na avaliaçäo de 2 semanas a média dos limiares de voltagem, foi de 0,57ñ0,04V para o Sweet Tip Rx e 1,0ñ0,19V para o Sweet Tip (p<0,02). Para os eletrodos ventriculares, essa média foi de 0,66ñ0,07V para o Sweet Tip Rx e 1,50ñ0,23V para o Sweet Tip (p<0,01). Para os eletrodos atriais os valores médios dos limiares de largura de pulso nesta etapa foram 0,10ñ0,02ms para o Sweet Tip Rx e 0,19ñ0,07ms para o Sweet Tip (p>0,49) e para os eletrodos ventriculares 0,14ñ0,02ms para o Sweet Tip Rx e 0,31ñ0,05ms para o Sweet Tip (p<0,01). Na última avaliaçäo, os valores médios dos limiares de largura de pulso dos eletrodos atriais foram 0,06ñ0,01ms para o Sweet Tip Rx e 0,14ñ0,05ms para o Sweet Tip (p<0,26) e, para os eletrodos ventriculares 0,09ñ0,01ms para o Sweet Tip Rx e 0,50ñ0,14ms para o Sweet Tip (p<0,01). Näo houve diferença significativa entre a impedância dos dois tipos de eletrodos nas avaliaçöes tardias. CONCLUSÄO: Os eletrodos envolvidos com esteróides tiveram um limiar significativamente menor após o implante.