Lymphocyte subsets early predict mortality in a large series of hospitalized COVID-19 patients in Spain.

The role of lymphocytes and their main subsets as prognostic factors of death in SARS-CoV-2-infected patients remains unclear, with no information obtained from patients outside China. We aimed to assess whether measuring lymphocyte subpopulations added clinical value to the total lymphocyte counting regarding mortality when they were simultaneously tested at hospital admission. Peripheral blood was analysed in 701 polymerase chain reaction (PCR)-confirmed consecutive patients by lysed-no washed flow cytometry. Demographic and clinical features were registered in electronic medical records. Statistical analysis was performed after a 3-month follow-up. The 112 patients who died were older and had significantly higher frequencies of known co-morbidities than survivor COVID-19 patients. A significant reduction in total lymphocytes, CD3+ , CD4+ , CD8+ and CD19+ counts and CD3+ percentage was found in the group of deceased patients (P < 0·001), while the percentage of CD56+ /CD16+ natural killer (NK) cells was significantly higher (P < 0·001). Multivariate logistic regression analysis showed a significantly increased risk of in-hospital death associated to age [odds ratio (OR) = 2·36, 95% confidence interval (CI) = 1·9-3·0 P < 0·001]; CD4+  T counts ≤ 500 cells/µl, (OR = 2·79, 95% CI = 1·1-6·7, P = 0·021); CD8+  T counts ≤ 100 cells/µl, (OR = 1·98, 95% CI = 1·2-3·3) P = 0·009) and CD56+ /CD16+ NK ≥ 30%, (OR = 1·97, 95% CI = 1·1-3·1, P = 0·002) at admission, independent of total lymphocyte numbers and co-morbidities, with area under the curve 0·85 (95% CI = 0·81-0·88). Reduced counts of CD4+ and CD8+ T cells with proportional expansion of NK lymphocytes at admission were prognostic factors of death in this Spanish series. In COVID-19 patients with normal levels of lymphocytes or mild lymphopenia, imbalanced lymphocyte subpopulations were early markers of in-hospital mortality.

Abacavir/lamivudine plus darunavir/ritonavir in routine clinical practice: a multicentre experience in antiretroviral therapy-naive and -experienced patients.

OBJECTIVES: To present clinical experience with a regimen including abacavir/lamivudine + darunavir/ritonavir in a cohort of HIV-1-infected patients. METHODS: A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine + darunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48. RESULTS: One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events. CONCLUSIONS: In our cohort, abacavir/lamivudine + darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.

Mycobacterium tuberculosis bacteremia in patients with and without human immunodeficiency virus infection.

PURPOSE: To determine the incidence of Mycobacterium tuberculosis bacteremia in a general hospital and to describe the clinical characteristics, therapy, and outcome of patients with bacteremic tuberculosis. PATIENTS AND METHODS: Clinical charts of all patients in whom M tuberculosis was isolated from blood cultures during a 5-year period were reviewed. Mycobacterium tuberculosis was detected by means of a nonradiometric blood culture system. RESULTS: Of 285 patients with culture-proved tuberculosis in whom blood cultures were obtained, 50 (14%) had M tuberculosis bacteremia. Of 42 patients analyzed, 34 (81%) were infected with human immunodeficiency virus (HIV) and eight (19%) were not infected with HIV. Blood was the only or the first positive specimen in 14 patients (33%). Most HIV-infected patients (79%) were intravenous drug users, and 40 (88%) had clinical and/or radiologic evidence of involvement of one or more organs. Lungs were affected in 71% of the patients. In-hospital mortality was 18% in HIV-infected patients with mycobacteremia. Among eight non-HIV-infected patients, four had an underlying disease, and none was immunosuppressed. Disseminated disease was diagnosed in three patients. Two patients died as a consequence of tuberculosis in this group. CONCLUSIONS: Mycobacterium tuberculosis bacteremia is common in HIV-infected patients and is possible in nonimmunosuppressed subjects. Blood cultures are helpful in making the diagnosis of tuberculosis and can help establish a diagnosis of disseminated infection.

Treatment of AIDS-associated progressive multifocal leukoencephalopathy with highly active antiretroviral therapy.

OBJECTIVES: To evaluate the efficacy of highly active antiretroviral therapy (HAART) in 12 patients with AIDS-associated progressive multifocal leukoencephalopathy (PML). PATIENTS AND METHODS: The diagnosis of PML was established by brain biopsy in six patients and by neuroimaging findings and PCR detection of JC virus in cerebrospinal fluid (CSF) in six patients. We also studied 13 consecutive AIDS patients with biopsy-proven PML cared for in the same institution before HAART was available. Eleven patients of the HAART group and eight patients of the control group received intravenous arabinoside cytosine cycles. RESULTS: With HAART, the median decrease in the HIV viral load was 3.58 log10 copies/ml and the median increase in the CD4 cell count was 74x10(6)/l. The median survival time after PML diagnosis was 545 days in the HAART group and 60 days in the control group (P<0.001, log-rank test). In the HAART group, the neurological deficits improved substantially in six patients and stabilized in six patients. Eleven patients underwent follow-up cranial computed tomography or magnetic resonance scan that showed improvement of PML lesions in 10 patients and stabilization in one patient. Follow-up CSF analysis showed clearance of JC virus in six out of seven patients who had an initial positive result. CONCLUSIONS: This study shows that HAART may increase the survival, clinical status and radiological features of AIDS patients with PML. Clearance of JC virus from CSF has been found, suggesting that immune reconstitution can interrupt the JC virus lytic cycle.

Group A streptococcal bacteremia. A 10-year prospective study.

In this paper we present a prospective evaluation of 100 patients with Group A Streptococcal (GAS) bacteremia evaluated in our hospital over a 10-year period. Sixty-two patients were intravenous drug users (IVDU); all but 1 of these had an obvious cutaneous portal of entry related to the injection of illicit drugs. Twenty-seven patients had infectious metastasis, and the presence of septic pulmonary embolism was associated with suppurative phlebitis. Four of these patients had endocarditis. In the non-IVDU group, 24 patients had an underlying disease, and 12 were immunosuppressed. In 14 cases the infection was of hospital acquisition; in 35% infection was related to medical manipulations. Comparing the IVDU and non-IVDU groups, GAS bacteremia in IVDU patients is associated with a more benign outcome, a longer time of evolution before diagnosis, and a lower frequency of septic shock and mortality than in non-IVDU patients. Although in the univariate analysis GAS bacteremia was associated with several variables, in the multivariate analysis only the presence of shock and nosocomial acquisition of the infection were independently associated with a fatal outcome. Fifty-two patients were infected with human immunodeficiency virus (HIV); 5 of these were in the non-IVDU group. During the last 5 years of study, GAS bacteremia in our hospital was 39 times more frequent in HIV-infected patients than in patients without HIV. Nine patients presented clinical criteria corresponding to Streptococcal toxic shock syndrome (STSS), although its incidence was lower in the IVDU group. In the non-IVDU group, STSS was more frequent in patients with a necrotizing portal of entry, an age between 20 and 40 years, women, and when the origin of the infection was the skin or soft tissue. Six patients with STSS died, and death was associated with the presence of necrotizing lesions and lower counts of white cells, platelets, or hemoglobin.

Ciprofloxacin in patients with bacteremic infections. The Spanish Group for the Study of Ciprofloxacin.

The efficacy and safety of ciprofloxacin in the treatment of 68 episodes of bacteremia were studied. Patients were treated intravenously (30 cases), orally (13 cases), or with sequential intravenous/oral therapy (25 cases). Intravenous doses ranged from 200 to 400 mg per day and oral doses ranged from 1,000 to 1,500 mg per day. According to the criteria of McCabe and Jackson, 39 cases had nonfatal and 29 had ultimately fatal underlying diseases. The clinical condition of patients at the start of therapy was critical or poor in 40 cases and fair or good in 28. Sixty-four of the 68 episodes of bacteremia were monomicrobial and the remaining four were polymicrobial. The causative micro-organisms were: Escherichia coli (18 episodes), Pseudomonas aeruginosa (13 episodes), Acinetobacter sp. (10 episodes), Salmonella sp. (seven episodes), Enterobacter sp. (six episodes), Proteus sp. (four episodes), Serratia sp. (four episodes), Haemophilus influenzae (three episodes), Klebsiella sp. (three episodes), Staphylococcus aureus (2 episodes), and Morganella morganii (two episodes). Overall clinical efficacy of ciprofloxacin was 94 percent (64 of 68 patients). Bacteremia persisted in four patients (failure rate of 6 percent). Five organisms persisted: Acinetobacter sp. (two patients), P. aeruginosa (one patient), Enterobacter sp. (one patient), and Serratia sp. (one patient). Side effects were phlebitis associated with intravenous administration (four cases), dizziness (four cases), and superinfection (six cases). Superinfecting organisms and sites were as follows: Enterococcus faecalis, wound (2 cases); Candida sp., urinary tract infection (one case); Acinetobacter anitratus (ciprofloxacin resistant), urinary tract infection (one case); Staphylococcus epidermidis, blood (one case); and Clostridium perfringens, blood (one case). Ciprofloxacin administered either intravenously, orally, or intravenously followed by the oral route is effective therapy in the treatment of severe bacteremic infections.

Long-term benefits of nevirapine-containing regimens: multicenter study with 506 patients, followed-up a median of 9 years.

OBJECTIVE: To evaluate long-term outcomes in patients maintaining a nevirapine (NVP)-based regimen. METHODS: Retrospective, multicenter, cohort study including patients currently receiving an NVP regimen that had been started at least 5 years previously. Demographic, clinical, and analytical variables were recorded. RESULTS: Median follow-up was 8.9 (5.7-11.3) years. Baseline characteristics: 74% men, 47 years old, 36% drug users, 40% AIDS, 40% HCV+, 51.4% detectable HIV-1 viral load, CD4 count 395 (4-1,421)/µL, 19% CD4 < 200/µL, 27% ALT grade 1-2, 36% AST grade 1-2. Thirty percent ART-naive, 83%received NVP associated with 2 nucleoside analogues during the study period, and 17% a protease inhibitor. A significant improvement was observed in general health status markers, including hemoglobin, platelets, and albumin, regardless of HCV coinfection. CD4 cell gain was +218 and +322/µL after 6 and 9 years, respectively (+321 and +391 in naive patients). Triglycerides significantly decreased in pretreated patients, whereas the percentage of patients with HDLc < 1.03 mmol/L and LDL-c > 3.37 mmol/L significantly decreased in a subsample with available values. A significant decrease in transaminases, alkaline phosphatase, and Fib4 score was observed, mainly in HCV+ and ARV-naive patients. CONCLUSIONS: In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability.

Comparison of bronchial washing, brushing and biopsy for diagnosis of pulmonary tuberculosis.

The diagnostic yields of bronchial washings, bronchial brushings and lung biopsy specimens were compared in 50 patients with positive Mycobacterium tuberculosis cultures. The number of positive results obtained with cultures of bronchial brushings was significantly higher than that with bronchial washings (p less than 0.001). The histological study of biopsy lung material improved the rate of immediate or rapid diagnosis of tuberculosis (p less than 0.001).

Cutaneous mucormycosis in a heart transplant patient associated with a peripheral catheter.

The first known case of an intravascular catheter-related primary cutaneous mucormycosis in a heart transplant patient is reported. The patient had corticosteroid-induced hyperglycemia and experienced an acute tissue rejection episode. A necrotic lesion appeared around the insertion site of a peripheral venous catheter. A biopsy revealed typical mucorales hyphae. The lesion continued to spread during the following 24 hours and necessitated amputation of the forearm. The organism was identified as a Mucor species.

Leuconostoc species as a cause of bacteremia: two case reports and a literature review.

Two new cases of significant bacteremia caused by Leuconostoc spp. are reported and five others described in the literature are reviewed. Four of the seven patients were under one year old and presented with prolonged diarrhea related to gastrointestinal disorders. The remaining three patients were over 50 years of age and being treated in intensive care units. Six patients had nosocomially acquired catheter-related bacteremia. Leuconostoc spp. are naturally resistant to vancomycin, and five patients had received this antibiotic for prior bacteremia caused by methicillin-resistant staphylococci. The majority of patients presented with fever without severe complications. Penicillin is the treatment of choice and there is no report of any death directly attributable to infection by these microorganisms. Infection with Leuconostoc spp. should be suspected if "vancomycin-resistant streptococci" are isolated from the blood, and recorded as a potential cause of bacteremia in patients with indwelling intravenous catheters.

Infections caused by erythromycin-resistant Streptococcus pneumoniae: incidence, risk factors, and response to therapy in a prospective study.

To evaluate the incidence and the significance of resistance to erythromycin among clinical isolates of Streptococcus pneumoniae, we identified and prospectively followed all hospitalized patients in a 27-month period who had the organism isolated from any clinical sample. Patients who had an infection caused by pneumococci resistant to erythromycin (minimum inhibitory concentration, > 1 microgram/mL) were compared to those with infections caused by erythromycin-susceptible organisms. The incidence of erythromycin resistance among pneumococci doubled over the study period (from 7.6% in 1988 to 15.2% in 1992). Most strains (94%) showed resistance to multiple antibiotics, including other macrolides. By multivariate analysis, an age of < 5 years and nosocomial acquisition of the infection were independent risk factors for erythromycin resistance. Among patients with pneumococcal pneumonia caused by erythromycin-resistant organisms, 9 patients treated with third-generation cephalosporins were cured, while therapy with erythromycin failed for 2 of the 6 patients to whom it was administered. The rapid and significant increase of erythromycin resistance among clinical isolates of S. pneumoniae points to the need for routine surveillance of pneumococcal resistance.

Enhanced activity of the combination of penicillin G and gentamicin against penicillin-resistant viridans group streptococci.

We evaluated the effects of the combination of penicillin G and gentamicin against 10 penicillin-resistant bacteremic isolates of viridans group streptococci for which the MICs of penicillin were 4 to 64 micrograms/ml. In time-kill studies, the combination resulted in more killing of eight isolates for which the MICs of penicillin were from 8 to 64 micrograms/ml than any of the antimicrobial agents tested alone. In general, clearly enhanced antimicrobial activity was observed with the combination.

Postsurgical mediastinitis: a case-control study.

We report the results of a case-control study of postsurgical mediastinitis (PSM) that we conducted from 1985 to 1993. The incidence of PSM was 2.2% (81 of 3,711 cases who underwent sternotomy); we analyzed the findings for 73 cases and 73 controls. Univariate analysis revealed that the risk factors for PSM were emergency surgery (27% of cases vs. 13% of controls), New York Heart Association functional class IV (46.5% vs. 21.9%), heart transplantation (12% vs. 0), and coronary artery bypass graft (CABG) surgery (60% vs. 41%). The incidences of fever, reoperation for bleeding, pacemaker placement, use of vasoactive drugs, prolonged mechanical ventilation, use of central lines, and treatment in the intensive care unit were also higher for cases. Multivariate analysis identified the following independent risk factors for PSM: reoperation (risk ratio [RR], 9.2), need for vasoactive drugs (RR, 3.5), CABG surgery (RR, 3.2), and fever that persisted after the third postsurgical day (RR, 406). The related mortality was 13.7%, and death was significantly more frequent among cases (17.7%) than among controls (2.7%). Multivariate analysis identified the following independent risk factors for mortality: bacteremia (RR, 21.5), the use of an intraaortic balloon (RR, 14.9), advanced age (RR, 1.14 per year), and prolonged mechanical ventilation (RR, 1.1 per day).

Epidemic outbreak of Serratia marcescens infection in a cardiac surgery unit.

Between 2 February and 16 April 1985, an outbreak of Serratia marcescens infection involving 10 male patients occurred in a cardiac surgery unit. All the patients had surgical wound infection, five also had osteomyelitis (four sternal, one costal), and another had peritonitis secondary to peritoneal dialysis. Three patients had concomitant bacteremia. All Serratia strains isolated produced a cherry-red pigment, and all had the same biochemical and antibiotic susceptibility pattern. An intensive search for the origin of the outbreak was initially unsuccessful, and it proved impossible to isolate S. marcescens from cultures of numerous samples taken from hospital personnel and from the environment. The fact that all patients were male and had been shaved for surgery by the same team of barbers led us to investigate the shaving procedures. We finally isolated a strain of pigmented S. marcescens, corresponding to that involved in the outbreak, from samples taken from the hands and equipment of the barbers. After suitable action had been taken, the epidemic terminated.

Impact of the BACTEC NR system in detecting Candida fungemia.

As a result of the growing importance of candidemia, various techniques for the detection of Candida spp. in blood have been designed with a view to speeding up the laboratory procedure. We have performed a retrospective comparison of the efficiencies of the conventional VACUTAINER system (Becton Dickinson Vacutainer Systems) and the BACTEC NR system (Johnston Laboratories, Inc.). During a 4-year period, 88,300 blood cultures were processed, with growth of Candida species in 552. The mean times required for the detection of growth were 7.55 days with the VACUTAINER system and 4.1 days with the BACTEC NR system (P less than 0.05). During the first week of incubation, the VACUTAINER system detected 56.1% of the candidemias and the BACTEC NR detected 93.6% (P less than 0.05). Use of the BACTEC NR therefore permits reduction of the incubation period from the previously established 4 weeks to a more convenient 7 to 14 days.

[Multicenter study of fluconazole in the treatment of oropharyngeal candidiasis in immunodepressed patients]. / Estudio multicéntrico de fluconazol en el tratamiento de la candidiasis orofaríngea en pacientes inmunodeprimidos.

We have evaluated the efficacy of fluconazole, 50 mg/day for 2 weeks, to treat oropharyngeal candidiasis in immunologically compromised patients. There were overall 27 patients, 25 of which were HIV+ and 2 had neutropenia. The rate of clinical response at the end of therapy, and one week and one month afterwards were 96%, 76% and 64%, respectively. The microbiological eradication was achieved in 36% of patients. The tolerance of the drug was satisfactory, although in 3 cases features of hepatic toxicity were detected. The convenience, good tolerance and clinical efficacy of fluconazole make it the therapy of choice for oropharyngeal candidiasis in immunologically compromised patients.