Economic burden of recurrent Clostridioides difficile infection in adults admitted to Spanish hospitals. A multicentre retrospective observational study.

OBJECTIVE: Clostridioides difficile infection (CDI) is associated with increased hospital stays and mortality and a high likelihood of rehospitalization, leading to increased health resource use and costs. The objective was to estimate the economic burden of recurrent CDI (rCDI). METHODS: Observational, retrospective study carried out in six hospitals. Adults aged ≥18 years with ≥1 confirmed diagnosis (primary or secondary) of rCDI between January 2010 and May 2018 were included. rCDI-related resource use included days of hospital stay (emergency room, ward, isolation and ICU), tests and treatments. For patients with primary diagnosis of rCDI, the complete hospital stay was attributed to rCDI. When diagnosis of rCDI was secondary, hospital stay attributed to rCDI was estimated using 1:1 propensity score matching as the difference in hospital stay compared to controls. Controls were hospitalizations without CDI recorded in the Spanish National Hospital Discharge Database. The cost was calculated by multiplying the natural resource units by the unit cost. Costs (euros) were updated to 2019. RESULTS: We included 282 rCDI episodes (188 as primary diagnosis): 66.31% of patients were aged ≥65 years and 57.80% were female. The mean hospital stay (SD) was 17.18 (23.27) days: 86.17% of rCDI episodes were isolated for a mean (SD) of 10.30 (9.97) days. The total mean cost (95%-CI) per episode was €10,877 (9,499-12,777), of which the hospital stay accounted for 92.56. CONCLUSIONS: There is high cost and resource use associated with rCDI, highlighting the importance of preventing rCDI to the Spanish National Health System.

Impact of pretransplant CMV-specific T-cell immune response in the control of CMV infection after solid organ transplantation: a prospective cohort study.

INTRODUCTION: Although solid organ transplant (SOT) recipients with pretransplant serology for cytomegalovirus (CMV-R+) are considered at intermediate risk for CMV infection post transplantation, CMV infection remains a major cause of morbidity in this population. We prospectively characterized whether having pretransplant CMV-specific cellular immunity is independently associated with controlling infection after transplantation in R + SOT recipients. METHODS: A prospective cohort of consecutive R + SOT recipients that received pre-emptive treatment for CMV infection was monitored after transplantation and variables were recorded during the follow-up. The cytomegalovirus-specific T-cell immune response was characterized by intracellular cytokine staining and viral loads determined using real-time PCR. RESULTS: One hundred and thirty-five R + SOT recipients were included (67 kidney, 64 liver, four liver-kidney). Only one-third of the patients (42; 31.85%) had CMV-specific T-cell immunity (CD8+CD69+INF-γ+ T cells >0.25%) before transplantation. Patients with negative pretransplant immunity had more CMV infection (49, 52.7% vs. 15, 35.7%; p 0.07) and received more antiviral therapy than those with immunity (32, 34.4% vs. 6, 14.3%, p 0.016). Having CMV specific immunity was an independent factor for protection from developing viraemia ≥2000 IU/mL (OR 0.276, 95% CI 0.105-0.725, p < 0.01) and lower administration of treatment (OR 0.398, 95% CI 0.175-0.905, p 0.028). Only patients with no pretransplant CMV-specific T-cell response were diagnosed with CMV-disease (8, 8.6% vs. 0, 0%, p 0.05). DISCUSSION: Our results show that having a pretransplant CMV specific T-cell response may be associated with a lower rate of CMV viraemia and less antiviral treatment after transplantation; however, more prospective studies are needed to confirm these findings.

Global impact of an educational antimicrobial stewardship programme on prescribing practice in a tertiary hospital centre.

The misuse of antibiotics has been related to increased morbidity, mortality and bacterial resistance. The development of antimicrobial stewardship programmes (ASPs) has been encouraged by scientific societies as an essential measure. An educational, institutionally supported ASP was developed in our tertiary-care centre. Local guidelines on the management of infectious syndromes were created. Antimicrobial prescriptions were chosen arbitrarily weekly and counselling interviews by expert clinicians were carried out, using a paedagogic, non-restrictive methodology. Satisfaction with the interview was assessed using anonymous questionnaires. The appropriateness of antimicrobial prescriptions as well as consumption was assessed prospectively throughout the year. Feedback regarding the correct use of treatments was communicated to each participating department periodically. The improvement in antimicrobial prescription was included among the annual objectives linked to economic incentives in every department. A total of 1206 counselling interviews were carried out during the first year. Fifty-three per cent of antimicrobial prescriptions (176/332) were inappropriate when the programme started. The rate of inappropriate prescriptions continuously declined to 26.4% (107/405) in the fourth trimester (p <0.001; RR = 0.38; 95% CI, 0.23-0.43). Antimicrobial consumption decreased from 1150 defined daily doses (DDDs) per 1000 occupied bed-days in the first trimester to 852 DDDs in the fourth, reflecting a reduction in antimicrobial expenditures of 42%. A total of 352 satisfaction questionnaires were received and 98% described the advice as positive. In conclusion, the implementation of an education-based ASP achieved a significant improvement in all antimicrobial prescriptions in the centre and a reduction in antimicrobial consumption, even when no restrictive measures were implemented. The programme was highly accepted by all prescribers.

Strongyloides stercoralis hyperinfection transmitted by liver allograft in a transplant recipient.

We describe a case of Strongyloides stercoralis hyperinfection in a liver allograft recipient 2.5 months after transplantation. The patient lives in Spain, which is not considered an endemic country for strongyloidiasis, and denied prior residence or travel to any known endemic area. The initial symptoms were fever and vomiting, and he subsequently developed a severe respiratory disease. An endoscopic biopsy of ulcerative lesions of the duodenum revealed massive mucosa infiltration by larvae and adult worms, which were also found in respiratory samples. The patient was successfully treated with combined therapy with albendazole and ivermectin. The strongyloides infection was transmitted by the liver allograft. The donor was from Ecuador and, retrospectively, his serum tested positive for S. stercoralis IgG antibodies. Additionally, the pancreas-left kidney allograft recipient from the same donor later developed an intestinal strongyloidiasis without hyperinfection syndrome. To our knowledge, this is the first confirmed case of S. stercoralis infection transmission from the same donor to two solid allograft recipients.

Colistin efficacy in an experimental model of Acinetobacter baumannii endocarditis.

The in-vivo activity of colistin was evaluated in an experimental rabbit model of Acinetobacter baumannii endocarditis with a strain susceptible to colistin and intermediate to imipenem. Compared to a control group, colistin was effective (p < 0.05) in bacterial clearance from blood and in the sterilisation of blood cultures, but was not effective in clearing A. baumannii from vegetations. Thus, although colistin may be effective in treating bacteraemia caused by susceptible strains of A. baumannii, it may not be a suitable treatment for endocarditis, perhaps because of poor penetration into vegetations and a low C(max)/MIC ratio in tissue.

Aspergillus fumigatus cranial infection after accidental traumatism.

Described here is a case of Aspergillus fumigatus cranial infection secondary to accidental cranial traumatism that occurred in an immunocompetent patient and the questions that arose concerning treatment. No reports of post-traumatic cranial osteomyelitis caused by Aspergillus spp. and the ideal treatment to be followed have yet been described in the literature. In the present case, surgical debridement of the wound followed by treatment with 1 mg/kg/iv/day of amphotericin B for 21 days and then 200 mg/vo/12 h of itraconazole for 6 months obtained good results.

Sulbactam efficacy in experimental models caused by susceptible and intermediate Acinetobacter baumannii strains.

Sulbactam and imipenem were compared in an experimental pneumonia model in immunocompetent mice, using a susceptible strain of Acinetobacter baumannii, and in an experimental endocarditis model in rabbits, using an intermediately susceptible strain. In the former, sulbactam was as efficacious as imipenem in terms of survival, sterility of lungs and in the bacterial clearance from lungs and blood, provided that the t > MIC for sulbactam (1.84 h) was similar to that for imipenem (2.01 h). In the endocarditis model, imipenem (t > MIC, 2.12 h) was more efficacious than sulbactam (t > MIC, 1.17 h) in bacterial clearance from vegetations. These results show the efficacy of sulbactam in infections caused by susceptible strains of A. baumannii, with an MIC up to 4 mg/L, provided that doses reach a t > MIC similar to that of imipenem. The activity of sulbactam was time dependent.

Imipenem, doxycycline and amikacin in monotherapy and in combination in Acinetobacter baumannii experimental pneumonia.

Acinetobacter baumannii is a common cause of nosocomial pneumonia and other nosocomial infections. Multiresistant A. baumannii has also a high prevalence, which can make effective treatment difficult. We designed a new model of A. baumannii experimental pneumonia using C57BL/6 immunocompetent mice. This model was used to compare the efficacy of imipenem, doxycycline and amikacin in monotherapy, and the combination of imipenem plus amikacin and doxycycline plus amikacin. Doxycycline plus amikacin were synergic in vitro after 24 h incubation, whereas imipenem plus amikacin showed no in vitro synergy. The number of sterile lungs and the lung clearance of A. baumannii were greater in the group treated with imipenem than in those treated with amikacin or doxycycline in monotherapy (P < 0.05). The combination of imipenem plus amikacin and doxycycline plus amikacin was no more effective than imipenem alone in the clearance of organisms from lungs (2.42 +/- 1.46 cfu/g versus 2.7 +/- 1.5 cfu/g versus 1.23 +/- 1.02 cfu/g). These results suggest that the addition of amikacin does not improve the results obtained by imipenem monotherapy. Doxycycline plus amikacin is an alternative to imipenem in the therapy of A. baumannii pneumonia.

[Clinical and immuno-virologic efficacy of the expanded access use of protease inhibitors for HIV-1 advanced disease]. / Eficacia clínica e inmunovirológica del uso compasivo de los inhibidores de proteasas en pacientes con infección avanzada por el VIH-1.

OBJECTIVE: To compare the efficacy and tolerance of additive therapy with protease inhibitors (PI) in patients with advanced HIV infection previously treated with retro-transcriptase inhibitors (RTI). METHODS: Eighty patients with prior antiretroviral therapy with RTI (zidovudine, ddI or ddc) for more than 6 months were included. Fifteen patients received indinavir, 42 ritonavir and 23 saquinavir. Data were collected at 4, 12 and 24 weeks and included clinical events, tolerability, plasma HIV-1 RNA viral load and CD4+ cell counts. Virologic response was defined if a viral load reduction > 1 log was achieved. RESULTS: Virological response was observed in 45 patients (56.5%) at 4 weeks and was maintained in most of them at 24 weeks. Viral load below limit of detection was achieved in 11 (15%) patients at 12 weeks. Adverse effects were not uncommon, specially with ritonavir, and 10 patients (12.5%) discontinued treatment. Indinavir was the most efficient drug and statistical differences in decreasing viral load were reached in pairwaise comparison with saquinavir at any time and with ritonavir at 12 and 24 weeks. CD4+ cell counts increased with all three drugs parallel with the decrease of viral load. Four patients died and 12 had opportunistic infections. Proportion of patients without infections in the follow-up was associated with virological response over treatment (p < 0.01). CONCLUSIONS: The additive therapy with PI in advanced HIV patients can achieve a sustained reduction of viral load and a persistent recovery of CD4+ cell counts with clinical benefits. Within the limits of this study, indinavir seems more interesting in this group of patients in terms of probability pursuit of treatment because of better efficiency and fewer adverse effects.

Atrial septal aneurysm. Is it a benign finding?

We report our clinical experience in a single centre with 7 cases of atrial septal aneurysm (ASA) diagnosed by transthoracic echocardiography (TTE) between 1989-1996. They did not present any clinical event compatible with cardiogenic embolism after a five years mean follow-up period. ASA is recognized as a potential source of cardiogenic embolism [2] based on some retrospective and selection biased studies.

[Aortic coarctation: different anatomo-clinical forms depending on the age of presentation]. / Coartación de aorta: diferentes formas anatomoclínicas según la edad de presentación.

OBJECTIVE: To analyse the anatomo-clinical characteristics of the coarctation of the aorta at different ages of presentation as well as the findings and results of its surgical correction at different periods. PATIENTS AND METHODS: We retrospectively studied the clinical and angiographic data, as well as the intraoperative findings and surgical outcomes of 82 consecutive patients (54 M and 28 F) with coarctation of the aorta. Mean age was 16.2 +/- 13.7 years (1 month to 63 years). The patients were divided into three groups according to age: Group A (n = 10) under 1 year; Group B (n = 30) from 1 to 12 years and Group C (n = 42) over 12 years. RESULTS: A preductal form was found in 20.7% cases (50.0%, 30.0% and 7.1% of groups A, B, and C respectively; p = 0.003). An associated left-to-right shunt was present in 19.5% (40.0%, 16.7% and 16.7% of groups A, B and C respectively; p = NS). The first manifestation of the disease was different in groups A, B and C. Among group A patients, congestive heart failure was the most frequent presentation (70.0%). In group B, the most frequent presentation (30%) was as an incidental finding in an asymptomatic patient. Finally, systemic hypertension or its complications predominated among group C patients (38.0%). Left ventricular hypertrophy on ECG was present in 0.0%, 30.0% and 54.7% of patients in groups A, B and C (p = 0.003) respectively. Postoperative complications including death, hypertensive crisis and re-coarctation were observed in 90.0%, 33.3% and 21.4% in groups A, B and C (p = 0.01) respectively. CONCLUSIONS: Among patients with coarctation of the aorta, the age of clinical presentation allows us to define groups of patients with different anatomical characteristics, clinical course and postoperative outcome.

Pneumonia after heart transplantation: a multi-institutional study. Spanish Transplantation Infection Study Group.

A multiinstitutional study of 307 heart transplant recipients was carried out to determine the clinical, radiographic, and prognostic characteristics, the incidence, and the etiology of pneumonias in the first year after transplantation. There were 21.1 cases of pneumonia per 100 heart transplantations. Seventy-five percent of the cases occurred in the first trimester. Eighty-two causal agents were identified, of which 60% were opportunistic, 25% were nosocomial, and 15% were community-acquired. The most frequent isolates were cytomegalovirus (20), Aspergillus species (13), and Pneumocystis carinii (11). Hemoptysis occurred more frequently in aspergillus pneumonias than in other pneumonias (54% vs. 6%, respectively; P < .05); aspergillus pneumonia was the only type of pneumonia during which cavitated nodules were noted on thoracic radiographs. The overall mortality rate was 30.8%; the independent factors of a poor prognosis were aspergillus infection (relative risk [RR], 7.4; 95% confidence interval [CI], 5.8-9.1) and bilateral pulmonary infiltrates (RR, 10; 95% CI, 8.5-11.4).

Suppurative mediastinitis after open-heart surgery: a comparison between cases caused by Gram-negative rods and by Gram-positive cocci.

OBJECTIVE: To compare clinical characteristics and risk factors of suppurative postsurgical mediastinitis according to its etiology. METHODS: Suppurative postsurgical mediastinitis developed in 45 (2.5%) of 1779 patients who underwent open-heart surgery at the Hospital Virgen del Rocío in Seville, Spain, from 1986 to 1996. Microbiological diagnosis was available in 42 patients. RESULTS: Gram-negative rods were isolated in 19 cases and Gram-positive cocci in 23 cases. Seventeen isolates (38%) were sensitive to the antimicrobial agent used perioperatively. Patients with Gram-negative rod infection had a longer duration of bypass (127plus minus36 min versus 96plus minus34 min, p<0.01), and a worse postoperative condition. Longer mechanical ventilation (4plus minus7 days versus 1plus minus2 days, p<0.05) and concomitant infection in a remote site (pulmonary and/or urinary infection) were more frequently observed in this group than in patients with Gram-positive infections (58% versus 22%, p<0.05). Twenty patients (51%) were bacteremic. The mortality rate was 20% (five of 45). CONCLUSIONS: Preventable postoperative remote-site infection may lead to mediastinitis, especially if Gram-negative rods are involved.

[Curative treatment with fluconazole in 5 cases of invasive candidiasis]. / Tratamiento curativo con fluconazol en 5 casos de candidiasis invasiva.

BACKGROUND: Amphotericin B is the treatment of choice for invasive and disseminated Candida sp. infections. Fluconazole is an antifungal drug with less toxicity. Because of its pharmacokinetic properties, fluconazole can be specially useful in the treatment of invasive candidiasis. Although it is useful in several forms of candidiasis, its efficacy in deep-seated candidal infections is not totally proved due to the lack of comparative studies with amphotericin. In order to contribute new data about the usefulness of fluconazole in the treatment of invasive candidiasis, we report 5 patients which cured with this antifungal drug. METHODS: The clinical records of those patients with invasive candidiasis that cured with fluconazole were retrospectively reviewed. RESULTS: Fluconazole was used in 2 patients after detecting toxicity to amphotericin. Fluconazole was used from the beginning in the other 3 patients. None of the patients were neutropenic. All the patients cured without recurrence. CONCLUSIONS: In this series, the employment of fluconazole was a non-toxic and effective alternative to amphotericin B in nonneutropenic patients with invasive candidiasis.