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.

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.

A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection. Grupo de Estudio del SIDA 04/98.

BACKGROUND: Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy. METHODS: We conducted a randomized trial of the discontinuation of primary or secondary prophylaxis against P. carinii pneumonia in HIV-infected patients with a sustained response to antiviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and plasma HIV type 1 (HIV-1) RNA level of less than 5000 copies per milliliter for at least three months. Prophylactic treatment was restarted if the CD4 cell count declined to less than 200 per cubic millimeter. RESULTS: The 474 patients receiving primary prophylaxis had a median CD4 cell count at entry of 342 per cubic millimeter, and 38 percent had detectable HIV-1 RNA. After a median follow-up period of 20 months (758 person-years), there had been no episodes of P. carinii pneumonia in the 240 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 0.85 episode per 100 person-years). For the 113 patients receiving secondary prophylaxis, the median CD4 cell count at entry was 355 per cubic millimeter, and 24 percent had detectable HIV-1 RNA. After a median follow-up period of 12 months (123 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.5 episodes per 100 person-years). CONCLUSIONS: In HIV-infected patients receiving highly active antiretroviral therapy, primary and secondary prophylaxis against P. carinii pneumonia can be safely discontinued after the CD4 cell count has increased to 200 or more per cubic millimeter for more than three months.

Progression of human immunodeficiency virus disease is associated with increasing disruptions within the CD4+ T cell receptor repertoire.

The immunodeficiency caused by human immunodeficiency virus (HIV) infection may be related to loss of diversity in the T cell receptor (TCR) repertoire. A cross-sectional study of the CD4 TCR repertoire was done for patients at various stages of HIV infection. Semiquantitative polymerase chain reaction was used to study the relative usage of the variable chain beta (BV) subfamilies and the size distributions of transcripts (CDR3 size analysis) within these subfamilies. The relative usage of the TCRBV subfamilies of patients and controls was not significantly different. The proportion of subfamilies with abnormal CDR3 size patterns was higher in the HIV-infected patients (25%, 95% confidence interval [CI], 17%-33%) than in the controls (7.2%, 95% CI, 2.3%-12.1%; P < .001), with a significant negative correlation between the number of CD4 cells and the percentage of abnormal TCRBV subfamilies. These results indicate that progressive loss of CD4 T cells is accompanied by increasing disruptions within the T cell receptor repertoire.

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.

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).

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.

Cytarabine therapy for progressive multifocal leukoencephalopathy in patients with AIDS.

To evaluate the efficacy and safety of intravenous cytarabine in the treatment of AIDS-associated progressive multifocal leukoencephalopathy (PML), we reviewed the charts of all human immunodeficiency virus-infected patients with PML who were seen during a 28-month period at our institution. Patients with biopsy-proven PML were offered therapy with intravenous cytarabine (2 mg/[kg.d] for 5 days every 4 weeks). The diagnosis of PML was histologically confirmed for 13 patients. The median CD4 cell count was 91 x 10(6)/L. A median of three courses of cytarabine was administered to eight patients. Two patients developed mild drug-related toxicities. Clinical and/or radiological signs of improvement were observed for three patients treated with cytarabine; no signs of improvement were noted for the untreated patients. Median survival time after the diagnosis of PML was 102 days (range, 46-220 days) for patients who received cytarabine and 60 days (range, 28-72 days) for untreated patients matched for Karnofsky scores (P = .06, logrank test). Although cytarabine is well tolerated by patients with AIDS and PML, only modest short-term clinical improvement in the conditions of patients treated with the drug has been observed, with no significant impact on survival.

Genetic dissimilarity of two fluconazole-resistant Candida albicans strains causing meningitis and oral candidiasis in the same AIDS patient.

We describe a patient with AIDS who simultaneously developed Candida meningitis with three positive cerebrospinal fluid cultures and oral candidiasis. This patient also had a history or recurrent episodes of oral candidiasis treated with fluconazole. The patient did not respond to this therapy but was cured with amphotericin B and flucytosine. In vitro susceptibility tests revealed that each infection was caused by fluconazole-resistant Candida albicans isolates. Strain delineation by karyotyping, NotI restriction pattern analysis, hybridization with the specific probe 27A, and PCR fingerprinting with the phage M13 core sequence clearly demonstrated that meningitis and oral thrush were caused by two genetically different isolates.

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.

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.

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.

Failure of cefotaxime in the treatment of meningitis due to relatively resistant Streptococcus pneumoniae.

To our knowledge, we report the first failure of cefotaxime in the treatment of meningitis due to relatively resistant Streptococcus pneumoniae (MICs of penicillin and cefotaxime, 1 microgram/mL). Cure was achieved with a 14-day course of intravenous and intrathecal vancomycin. We recommend that in cases of meningitis caused by strains of S. pneumoniae for which MICs are > or = 1 microgram/mL, cefotaxime should be used with caution; however, if therapeutic failure is suspected therapy should be changed to intravenous and intrathecal vancomycin.

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.

Susceptibility of Streptococcus pneumoniae to penicillin: a prospective microbiological and clinical study.

We performed a prospective study of all infections with Streptococcus pneumoniae documented during a 22-month period at our hospital. A total of 163 clinically significant strains of S. pneumoniae were isolated from 139 patients whose ages ranged from 8 days to 91 years (mean +/- SD, 42.6 years +/- 26.8 years). Twenty percent of the patients had cancer, and 18% were infected with the human immunodeficiency virus. Pneumococcal infection was nosocomially acquired in one-fourth of cases. One-third of patients had nonpneumonic disease. A wide range of serotypes were isolated, and 42.5% of all strains were nonsusceptible--i.e., showed either intermediate or high-level resistance--to penicillin. The rates of resistance to chloramphenicol, erythromycin, and tetracycline were 23%, 10.8%, and 48.2%, respectively. Twenty-two percent of the infected patients died, with a 15.8% mortality directly attributable to pneumococcal infection. Factors associated with infection by strains of S. pneumoniae not susceptible to penicillin included an age of less than or equal to 10 years, immunosuppression, the presence of a rapidly fatal underlying disease, previous antimicrobial therapy, and infection by serotypes 14 and 23. All clinically significant isolates of S. pneumoniae should be submitted for antimicrobial susceptibility studies, and, whenever a high prevalence of resistance to penicillin and macrolides is detected, the use of these well-established empirical therapeutic regimens should be reconsidered.

Group B Streptococcus: a cause of urinary tract infection in nonpregnant adults.

Group B Streptococcus (GBS) is a well-known cause of infection in the perinatal and puerperal periods, but its role as a urinary tract pathogen of adults in nonobstetric situations has not yet been defined. We carried out a prospective 19-month study of all nonpregnant adult patients with significant GBS bacteriuria. This microorganism accounted for 2% of positive urine cultures. Our series included 60 patients, 85% of whom were women and 95% of whom had at least one underlying condition. Urinary tract abnormalities (60%) and chronic renal failure (27%) were among the most frequent underlying problems. The infection was community acquired in 65% of cases. Clinical manifestations were related equally to the upper and the lower urinary tract (37% and 38% of cases, respectively). The clinical outcome was poor in 18% of episodes despite treatment. All isolates were sensitive to all antibiotics tested except gentamicin. We conclude that GBS is a significant urinary pathogen in nonpregnant adults and that its presence signals a need for screening for urinary tract abnormalities.