acyclovir and Critical-Illness

Latent cytomegalovirus (CMV) infection is present in more than half the adult population, and a viral reactivation (ie, when the virus becomes measurable in body fluids such as blood) can occur in up to one-third of these individuals during episodes of critical illness.. To determine whether antiviral therapy is safe and effective for preventing CMV reactivation in a general population of critically ill patients.. A single-center, open-label, randomized, controlled clinical trial recruited 124 CMV-seropositive patients undergoing mechanical ventilation for at least 24 hours in the intensive care unit between January 1, 2012, and January 31, 2014. The mean baseline Acute Physiology and Chronic Health Evaluation II score of all patients was 17.6.. Patients were randomized to receive anti-CMV prophylaxis with valacyclovir hydrochloride (n = 34) or low-dose valganciclovir hydrochloride (n = 46) for up to 28 days to suppress viral reactivation, or to a control group with no intervention (n = 44).. Time to first CMV reactivation in blood within the 28-day follow-up period following initiation of the study drug.. Among the 124 patients in the study (46 women and 78 men; mean [SD] age, 56.9 [16.9] years), viral reactivation in the blood occurred in 12 patients in the control group, compared with 1 patient in the valganciclovir group and 2 patients in the valacyclovir group (combined treatment groups vs control: hazard ratio, 0.14; 95% CI 0.04-0.50). Although this trial was not powered to assess clinical end points, the valacyclovir arm was halted prematurely because of higher mortality; 14 of 34 patients (41.2%) had died by 28 days, compared with 5 of 37 (13.5%) patients in the control arm at the point of the decision to halt this arm. Other safety end points showed similar outcomes between groups.. Antiviral prophylaxis with valacyclovir or low-dose valganciclovir suppresses CMV reactivation in patients with critical illness. However, given the higher mortality, a large-scale trial would be needed to determine the clinical efficacy and safety of CMV suppression.. clinicaltrials.gov Identifier: NCT01503918.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Critical Illness; Cytomegalovirus; Cytomegalovirus Infections; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Opportunistic Infections; Respiration, Artificial; Valacyclovir; Valine; Virus Activation; Virus Inactivation

Continuous venovenous hemodiafiltration (CVVHDF) is one of the treatments of critically ill children presenting severe acute liver failure. This affliction might be induced by HSV infection requiring a treatment by acyclovir. Continuous kidney replacement therapy (CKRT) can alter its pharmacokinetics, according to its physicochemical properties and CVVHDF settings.. This case describes acyclovir pharmacokinetics during CKRT in a pediatric patient treated by acyclovir. The patient was treated with adapted exposure with the usual dosing, but lower dosing should be investigated with complementary studies.. ClinicalTrials.gov NCT02539407.

Topics: Acute Kidney Injury; Acyclovir; Child; Continuous Renal Replacement Therapy; Critical Illness; Dialysis Solutions; Female; Hemodiafiltration; Humans; Infant; Liver Failure, Acute

To describe the prevalence, associated factors, and clinical impact of an initial negative herpes simplex virus (HSV) polymerase chain reaction (PCR) in critically ill patients with PCR-proven HSV encephalitis.. Retrospective multicenter study from 2007 to 2017.. Forty-seven French ICUs.. Critically ill patients admitted to the ICU with possible/probable acute encephalitis and a positive cerebrospinal fluid (CSF) PCR for HSV.. None.. We included 273 patients with a median Glasgow Coma Scale score of 9 (6-12) at ICU admission. CSF HSV PCR was negative in 11 cases (4%), exclusively in lumbar punctures (LPs) performed less than 4 days after symptoms onset. Patients with an initial negative PCR presented with more frequent focal neurologic signs (4/11 [36.4%] vs 35/256 [13.7%]; p = 0.04) and lower CSF leukocytosis (4 cells/mm3 [3-25 cells/mm3] vs 52 cells/mm3 [12-160 cells/mm3]; p < 0.01). An initial negative PCR was associated with an increased delay between LP and acyclovir treatment (3 d [2-7 ] vs 0 d [0-0 d]; p < 0.01) and was independently associated with a poor neurologic outcome at hospital discharge (modified Rankin Scale score ≥ 4) (adjusted odds ratio, 9.89; 95% CI, 1.18-82.78).. In severe herpes simplex encephalitis, initial negative CSF HSV PCR occurred in 4% of cases and was independently associated with worse neurologic outcome at hospital discharge. In these patients, a systematic multimodal diagnostic approach including early brain MRI and EEG will help clinicians avoid delayed acyclovir initiation or early inappropriate discontinuation.

Topics: Acyclovir; Cerebrospinal Fluid; Critical Illness; Encephalitis, Herpes Simplex; Humans; Polymerase Chain Reaction; Prevalence; Simplexvirus

Intraosseous (IO) access offers a fast and reliable route for administration of fluids and drugs when intravenous (IV) accesses like umbilical, peripheral, or peripherally inserted central lines fail in critically ill neonates. Several medications can be successfully administered via the IO route, however only limited information is available regarding IO administration of antiviral agents.We present the case of a 2-week-old neonate, admitted to the Neonatal Intensive Care Unit (NICU) due to suspected meningitis, who received acyclovir through IO infusion after the venous access was lost and a new one could not be established. No complications were reported within 12 months of follow up.This report highlights the feasibility of IO acyclovir infusion when IV accesses fail in a critically ill neonate.

Topics: Acyclovir; Critical Illness; Humans; Infant, Newborn; Infusions, Intraosseous; Tibia

Topics: Acyclovir; Critical Illness; Herpes Simplex; Humans; Respiration, Artificial; Simplexvirus; Virus Activation

Pulmonary pathogenicity of herpes simplex virus type 1 in patients in intensive care without classic immunosuppression as well as the necessity of antiviral treatment in the case of herpes simplex virus detection in respiratory specimens in these patients is controversial. We present a case of acute respiratory distress syndrome in a patient with stable chronic lymphatic leukemia not requiring treatment, in whom we diagnosed herpes simplex virus type 1 bronchopneumonitis based on herpes simplex virus type 1 detection in bronchoalveolar lavage fluid and clinical response to antiviral treatment.. A 72-year-old white man presented with symptoms of lower respiratory tract infection. His medical history was significant for chronic lymphatic leukemia, which had been stable without treatment, arterial hypertension, multiple squamous cell carcinomas of the scalp, and alcohol overuse. Community-acquired pneumonia was suspected and appropriate broad-spectrum antibacterial treatment was initiated. Within a few hours, rapid respiratory deterioration led to cardiac arrest. He was successfully resuscitated, but developed acute respiratory distress syndrome. Furthermore, he remained febrile and inflammation markers remained elevated despite antibacterial treatment. Polymerase chain reaction from bronchoalveolar lavage fluid and viral culture from tracheobronchial secretions tested positive for herpes simplex virus type 1. We initiated antiviral treatment with acyclovir. Concomitantly we further escalated the antibacterial treatment, although no bacterial pathogen had been isolated at any point. Defervescence occurred rapidly and his C-reactive protein and leukocyte levels decreased. He was successfully weaned from mechanical ventilation, transferred to the ward, and eventually discharged to home.. Herpes simplex virus should be considered a cause for lower respiratory tract infection in critically ill patients, especially in the setting of an underlying disease.

Topics: Acyclovir; Aged; Antiviral Agents; Bronchoalveolar Lavage Fluid; Critical Illness; Herpesvirus 1, Human; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Pneumonia; Respiratory Distress Syndrome; Treatment Outcome

Topics: Acyclovir; Administration, Intravenous; Antacids; Antiviral Agents; Coronary Artery Bypass; Critical Illness; Endoscopy, Digestive System; Esophagitis; Esophagogastric Junction; Esophagus; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunohistochemistry; Middle Aged; Peptic Ulcer Hemorrhage; Postoperative Complications; Proton Pump Inhibitors; Treatment Outcome

The relevance of the detection of herpes simplex virus type 1 (HSV-1) in the respiratory tract of patients in the intensive care unit (ICU) is unclear. Therefore, it is uncertain whether treatment with an antiviral agent could be beneficial for these patients.. We retrospectively reviewed the records of ICU patients with a positive HSV-1 culture in the respiratory tract or bronchoalveolar lavage (BAL) fluid. We evaluated whether acyclovir treatment (n=106) could have a beneficial effect on mortality as compared with the standard treatment (n=106).. Acyclovir treatment was positively linked to in-hospital and ICU-mortality reduction. This favourable influence remained present after correcting for possible confounders and using propensity-adjusted and propensity-matched cohorts: with an odds ratio in the treated group of 3.19 (95% CI 1.79-5.69, p=0.001) for ICU survival and of 3.55 (95% CI 2.16-5.85, p<0.001) for in-hospital survival. The subgroup with HSV-1 detected in the BAL-fluid is the sole contributor to this difference. In the BAL-fluid detected group, 48% (n=10) of non-treated patients died in the ICU, versus 21% (n=6) in the acyclovir-treated group (p=0.033), occurring despite an even longer duration of ventilation or ICU stay.. These data highlight the hypothesis that it might be worthwhile to consider treatment of HSV-1 in ICU patients depending on the type of respiratory sample in which the virus is detected. These results warrant a prospective trial to prove causality.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Bronchoalveolar Lavage Fluid; Critical Care; Critical Illness; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Intensive Care Units; Male; Middle Aged; Respiratory Tract Infections; Retrospective Studies; Risk Factors; Severity of Illness Index; Treatment Outcome; Young Adult

Varicella-zoster virus (VZV) usually causes localized zoster in adults. However, in immunocompromised patients, it can cause systemic infection accompanied by complications such as pneumonia, encephalitis, and hepatitis. Although most of critically ill patients in intensive care unit (ICU) are immunologically compromised, they are usually not considered to be at risk for systemic VZV infection.We report two cases of systemic VZV infection occurring in critically ill patients in an ICU. One patient was a 69-year-old man with Streptococcus pneumoniae-induced purpurafulminans, and the other was a 75-year-old woman with severe acute pancreatitis. During the clinical course in the ICU, characteristic vesicles with umbilical fossa appeared diffusely and bilaterally on their face, trunk, and extremities. VZV-specific IgG levels were confirmed to be elevated compared to that of the pre-onset, and a diagnosis of recurrent VZV infection was made in both patients. The patients were treated at the same ICU but did not coincide with each other; therefore a cross-infection was unlikely. They were treated with intravenous acyclovir, but the latter patient eventually died of respiratory failure.VZV infection can cause a number of serious complications, and can lead to death in some patients. Early detection and proper treatment are needed to prevent the infection from spreading out and save the patients. It might be necessary to consider antiviral prophylaxis against VZV infection for a part of critically ill patients in ICU, although the effectiveness of this approach is yet to be established.

Topics: Acyclovir; Administration, Intravenous; Aged; Animals; Antibodies, Viral; Critical Illness; Female; Herpesvirus 3, Human; Humans; Immunoglobulin G; Intensive Care Units; Male; Middle Aged; Pancreatitis; Pneumococcal Infections; Purpura Fulminans; Viremia

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Bronchoalveolar Lavage Fluid; Cohort Studies; Critical Illness; Female; Herpes Simplex; Humans; Incidence; Intubation, Intratracheal; Male; Middle Aged; Pneumonia, Viral; Respiratory Tract Infections; Retrospective Studies; Risk Assessment; Sensitivity and Specificity; Simplexvirus; Treatment Outcome

Herpes simplex infections are potentially a life-threatening situation for immunocompromised as well as critically ill patients. The correct diagnosis is made more difficult in comatose patients by the fact that the characteristic symptom of extreme pain cannot be registered. The clinical dermatological findings (polycyclic configuration, easily bleeding ulcers) are thus especially important in patients under intensive care conditions. As examples, the cases of 3 critically ill patients (subarachnoid bleeding or head injury) developing therapy-resistant, flat sacral or perioral skin ulcers with peripheral blisters are presented. Herpes simplex virus was confirmed immunohistologically and in the smear test. All patients subsequently died. These cases emphasize that patients in the intensive care unit are in danger of developing a chronic persistent Herpes simplex infection due to latent immunosuppression. Chronic persistent Herpes infections may be underrated in intensive therapy, and must always be ruled out in case of therapy-resistant erosions or ulcerations.

Topics: Acyclovir; Aged; Craniocerebral Trauma; Critical Care; Critical Illness; Fatal Outcome; Female; Herpes Simplex; Humans; Immunohistochemistry; Immunosuppression Therapy; Male; Reverse Transcriptase Polymerase Chain Reaction; Skin; Skin Ulcer; Subarachnoid Hemorrhage, Traumatic

A 73-year-old man with multiorgan failure requiring mechanical ventilation and haemodialysis developed herpes labialis infection during his stay in the ICU. This was treated with enteral acyclovir. He developed persistent neurologic impairment soon after acyclovir administration, which, over the course of seven days, progressed to coma, the aetiology of which was unclear. The computed tomograph (CT) of the brain and the cerebrospinal fluid (CSF) examination was normal. The electroencephalogram (EEG) showed generalized slowing. The possibility of acyclovir neurotoxicity was considered and the drug was discontinued. Haemodialysis was instituted and the patient made a complete neurological recovery. We believe that this is the first reported case of coma due to enteral acyclovir.

Topics: Acyclovir; Administration, Oral; Aged; Antiviral Agents; Brain; Cerebrospinal Fluid; Coma; Critical Care; Critical Illness; Electroencephalography; Herpes Labialis; Humans; Male; Multiple Organ Failure; Renal Dialysis; Respiration, Artificial; Tomography, X-Ray Computed