Co-infections and superinfections complicating COVID-19 in cancer patients: A multicentre, international study.

BACKGROUND: We aimed to describe the epidemiology, risk factors, and clinical outcomes of co-infections and superinfections in onco-hematological patients with COVID-19. METHODS: International, multicentre cohort study of cancer patients with COVID-19. All patients were included in the analysis of co-infections at diagnosis, while only patients admitted at least 48 h were included in the analysis of superinfections. RESULTS: 684 patients were included (384 with solid tumors and 300 with hematological malignancies). Co-infections and superinfections were documented in 7.8% (54/684) and 19.1% (113/590) of patients, respectively. Lower respiratory tract infections were the most frequent infectious complications, most often caused by Streptococcus pneumoniae and Pseudomonas aeruginosa. Only seven patients developed opportunistic infections. Compared to patients without infectious complications, those with infections had worse outcomes, with high rates of acute respiratory distress syndrome, intensive care unit (ICU) admission, and case-fatality rates. Neutropenia, ICU admission and high levels of C-reactive protein (CRP) were independent risk factors for infections. CONCLUSIONS: Infectious complications in cancer patients with COVID-19 were lower than expected, affecting mainly neutropenic patients with high levels of CRP and/or ICU admission. The rate of opportunistic infections was unexpectedly low. The use of empiric antimicrobials in cancer patients with COVID-19 needs to be optimized.

Administration of taurolidine-citrate lock solution for prevention of central venous catheter infection in adult neutropenic haematological patients: a randomised, double-blinded, placebo-controlled trial (TAURCAT).

BACKGROUND: Catheter-related bloodstream infection (CRBSI) is one of the most frequent complications in patients with cancer who have central venous catheters (CVCs) implanted and is associated with substantial morbidity and mortality. Taurolidine is a non-antibiotic agent with broad-spectrum antimicrobial activity, which has been used as a lock solution to prevent CRBSI in some settings. However, little is known about its usefulness in high-risk adult neutropenic patients with cancer. This prospective randomised clinical trial aims to test the hypothesis that taurolidine-citrate lock solution is more effective than placebo for preventing catheter infection in neutropenic haematological patients. METHODS: This study is a prospective, multicentre, randomised, double-blinded, parallel, superiority, placebo-controlled trial. Patients with haematological cancer who are expected to develop prolonged neutropenia (> 7 days) and who have a non-tunnelled CVC implanted will be randomised to receive prophylactic taurolidine-citrate-heparin solution using a lock technique (study group) or heparin alone (placebo group). The primary endpoint will be bacterial colonisation of the CVC hubs. The secondary endpoints will be the incidence of CRBSI, CVC removal, adverse events, and 30-day case-fatality rate. DISCUSSION: The lock technique is a preventive strategy that inhibits bacterial colonisation in the catheter hubs, which is the initial step of endoluminal catheter colonisation and the development of infection. Taurolidine is a nontoxic agent that does not develop antibiotic resistance because it acts as an antiseptic rather than an antibiotic. Taurolidine has shown controversial results in the few trials conducted in cancer patients. These studies have important limitations due to the lack of data on adult and/or high-risk neutropenic patients, the type of catheters studied (tunnelled or ports), and the lack of information regarding the intervention (e.g. dwelling of the solution, time, and periodicity of the lock technique). If our hypothesis is proven, the study could provide important solid evidence on the potential usefulness of this preventive procedure in a population at high risk of CRBSI, in whom this complication may significantly impair patient outcome. TRIAL REGISTRATION: ISRCTN, ISRCTN47102251 . Registered on 9 September 2015.

Clinical utility of real-time polymerase chain reaction to quantify cytomegalovirus replication in allogeneic stem cell transplant recipients with different prevention strategies.

Cytomegalovirus (CMV) end-organ disease is a serious, frequent complication after allogenic stem cell transplantation (Allo-SCT). There are two prevention strategies: universal prophylaxis and preemptive therapy. Preemptive therapy is administered based on the results of sensitive techniques that detect the viral infection. We analyzed 41 peripheral blood Allo-SCT recipients: 34 received prophylaxis and seven preemptive treatment. Viral infections determined using real-time polymerase chain reaction (RT-PCR) assays occurred at an overall incidence of 65.8%. The viral loads quantified by RT-PCR were compared among the prophylaxis versus the preemptive group. Overall, the median viral load was significantly higher in the preemptive compared with the prophylaxis group (P=.002). Furthermore, within the first 100 days posttransplantation, viral load values were higher among patients undergoing preemptive therapy (P=.009).

Differences in cytomegalovirus replication quantified using quantitative polymerase chain reaction and antigenemia after allogeneic stem cell transplantation.

Fifty percent of allogeneic stem cell recipients develop cytomegalovirus (CMV) infection in the first 100 days posttransplantation. Various methods have been used to determine CMV infections, including antigenemia assay and real-time polymerase chain reaction (RT-PCR). Although antigenemia assay has been used more frequently, this technique is less sensitive than RT-PCR. In contrast, RT-PCR has a low positive predictive value for CMV end-organ disease. Cytomegalovirus infections were analyzed in 41 peripheral blood samples from allogeneic stem cell recipients using both antigenemia assay and RT-PCR; results were discordant in 36.6% of patients. Although the antigenemia assay detected CMV replication in 29.2% of cases, RT-PCR was positive in 65.8%. In 83.3% of patients, results detected using the antigenemia assay were delayed by a median (range) of 5 (2-20) weeks compared with positive RT-PCR results. Within the first 100 days posttransplantation, higher levels of viral replication measured using RT-PCR were observed in patients with vs without antigenemia. In addition, in patients with antigenemia, viral load was significantly higher before day 100 than after (P=.01 and P=.008, respectively) compared with those without antigenemia.

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.

Preemptive therapy for cytomegalovirus disease in allogeneic stem cell transplant recipients.

Cytomegalovirus (CMV) infection causes high morbidity and mortality among allogeneic stem cell transplant recipients. Preemptive therapy with oral valganciclovir or intravenous ganciclovir has replaced universal prophylaxis. We prospectively studied 19 consecutive adult recipients of allogeneic peripheral blood stem cell transplants from May 2005 through February 2007 to analyze the safety and efficacy of preemptive therapy for the treatment of CMV infection. The antigenemia test was persistently negative in 8 patients (42%) and positive at least once in 11 (58%). Eight patients were treated with oral valganciclovir on an outpatient basis and they all became CMV negative after the first week of treatment. The other 3 patients received intravenous ganciclovir and were also CMV negative after the first week of treatment. No patient abandoned treatment, no severe secondary toxicity was noted, and there was no CMV-associated mortality.

[Pulmonary infiltrates and fever in a HIV infected patient after Pneumocystis jirovecii pneumonia]. / Infiltrado pulmonar y fiebre tras la resolución de neumonía por Pneumocystis jirovecii en un paciente con infección por el VIH.

In HIV-infected patients, cytomegalovirus (CMV) disease diagnosis is usually difficult and disease results from reactivation of latent infection or reinfection in the context of severe immunosupression. Although the introduction of highly active antiretroviral therapy (HAART) has resulted in a important decline of CMV disease, it has considerable morbidity and mortality rate. We present a case of a patient who presented fever, pulmonary infiltrates and abdominal pain after P.jirovecii pneumonia, with isolated of CMV (positive shell-vial) from LBA and gastric biopsy. We propose a possible diagnosis of digestive and pulmonary CMV disease and we initiated treatment for this with clinical response. It results surprising the rapid progression to SIDA of the patient and we can suggest that a co-infection HIV-CMV could be the cause for the rapid immunological damage.