COVID-19 rebound after oral treatment in a nursing home facility: A case series.

Paxlovid (nirmatrevir/ritonavir) is a 2 drug regimen taken together twice daily for 5 days was authorized for emergency use for nonhospitalized patients who are at risk for the progression of coronavirus disease (COVID-19). However, recurrence of symptoms 2-8 days after completing the treatment course has been recently recognized. In some cases patients tested negative on a direct SARS-CoV-2 viral test and then tested positive again (rebound COVID-19). The disease is mild and requires no additional antiviral treatment. Data are limited based on anecdotal case reports and few studies. According to the available data it is unclear if rebound symptoms are due to the drug treatment, drug resistance, re-infection or impaired immunity.

Administration of human protein C improves survival in an experimental model of sepsis.

OBJECTIVE: Study the effect of human protein C (PC) concentrate administration on organ damage and survival in septic rats. DESIGN: Animal study. SETTING: University laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Cecal ligation and puncture (CLP) was performed in 210 rats. Rats were randomly assigned to receive either human protein C (PC) IV 1, 7, and 13 hrs after CLP (CLP+PC) or placebo (CLP). Septic animals were again randomized in a survival group (CLP: n = 50 and CLP+PC: n = 40) that was monitored for 60 hrs and time groups (CLP: n = 60 and CLP+PC: n = 60) that were killed at 6, 12, 24, 36, 48, and 60 hrs after CLP. Brain, heart, lung, liver, kidney, gastric, and colon tissue were removed and postfixed in paraffin sections. MEASUREMENTS AND MAIN RESULTS: PC infusion increased PC serum levels in early sepsis (median 7.25) compared with late sepsis (median 2, p = .001). Activated protein C/a1-antitrypsin complex levels in the CLP+PC group were significantly increased in late sepsis (60 hrs after CLP) compared with early sepsis (6, 12, and 24 hrs after CLP, p = .009, p = .004, and p = .008, respectively) and to late septic CLP and normal rats (p = .005 and p = .007, respectively). Their IL-6 and tumor necrosis factor a plasma levels were decreased (by 27% and 25%, respectively) at 6 hrs compared with placebo (p = .008 and p = .016). Their serum PC levels were also decreased in CLP+PC survivors compared with nonsurvivors of the same group (median = 1.5 vs. median = 7, p = .001). Apoptosis was reduced in brain (10% vs. 77.8%, p < .001), stomach (66.7% vs. 100%, p < .002) and intestine (33.3% vs. 85.2%, p < .001) compared with placebo. Finally, the survival of septic rats treated with human PC was significantly increased compared with placebo (75% vs. 54%, p = .033). CONCLUSIONS: Human Protein C administration increased survival in septic rats, decreased plasma inflammatory cytokines levels and tissue injury in vital organs.

Oral atovaquone for the treatment of severe Pneumocystis jirovecii pneumonia in a patient with glucose-6-phosphate dehydrogenase deficiency.

We present a case of severe Pneumocystis jirovecii pneumonia and coexisting cytomegalovirus infection in a glucose-6-phosphate dehydrogenase (G6PD) enzyme deficient woman with anaplastic astrocytoma on temozolomide and corticosteroid therapy. She was successfully treated with oral atovaquone and ganciclovir. Atovaquone represents a safe alternative in severe Pneumocystis infection when trimethoprim-sulfamethoxazole (co-trimoxazole) is contraindicated.

Reasons of PEG failure to eliminate gastroesophageal reflux in mechanically ventilated patients.

AIM: To investigate factors predicting failure of percutaneous endoscopic gastrostomy (PEG) to eliminate gastroesophageal reflux (GER). METHODS: Twenty-nine consecutive mechanically ventilated patients were investigated. Patients were evaluated for GER by pH-metry pre-PEG and on the 7th post-PEG day. Endoscopic and histologic evidence of reflux esophagitis was also carried out. A beneficial response to PEG was considered when pH-metry on the 7th post-PEG day showed that GER was below 4%. RESULTS: Seventeen patients responded (RESP group) and 12 did not respond (N-RESP) to PEG. The mean age, sex, weight and APACHE II score were similar in both groups. GER (%) values were similar in both groups at baseline, but were significantly reduced in the RESP group compared with the N-RESP group on the 7th post-PEG day [2.5 (0.6-3.8) vs 8.1 (7.4-9.2, P < 0.001)]. Reflux esophagitis and the gastroesophageal flap valve (GEFV) grading differed significantly between the two groups (P = 0.031 and P = 0.020, respectively). Histology revealed no significant differences between the two groups. CONCLUSION: Endoscopic grading of GEFV and the presence of severe reflux esophagitis are predisposing factors for failure of PEG to reduce GER in mechanically ventilated patients.

Ampicillin-sulbactam: an update on the use of parenteral and oral forms in bacterial infections.

Ampicillin-sulbactam has a wide range of antibacterial activity that includes Gram-positive and Gram-negative aerobic and anaerobic bacteria. However, the drug is not active against Pseudomonas aeruginosa and pathogens producing extended-spectrum beta-lactamases. The combination could be considered particularly active against Acinetobacter baumannii infections due to the intrinsic activity of sulbactam. The drug is indicated as empirical therapy for a broad range of community acquired infections supervened in adults or children and is effective in either parenteral (ampicillin-sulbactam) or oral (as a mutual prodrug sultamicillin) form. In clinical trials, sultamicillin has proved clinically and bacteriologically effective in adults and children against a variety of frequently encountered infections, including mild upper and lower respiratory tract infections, urinary tract infections, diabetic foot and skin and soft tissue infections. Furthermore, adverse effects rarely occur with the diarrhoea to represent the most commonly reported. The parenteral ampicillin-sulbactam is indicated for community infections of mild-to-moderate severity acquired infections such as intra-abdominal or gynecological. Moreover, it seems to represent the alternative of choice for the treatment of A. baumannii infections for carbapenem-resistant strains in the nosocomial setting. Thus, ampicillin-sulbactam remains a valuable agent in the physician's armamentarium in the management of adult and pediatric infections.

Efficacy and safety of high-dose ampicillin/sulbactam vs. colistin as monotherapy for the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia.

OBJECTIVE: To compare the safety and efficacy of ampicillin/sulbactam (Amp/Sulb) and colistin (COL) in the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP). METHODS: A prospective cohort study in adult critically ill patients with VAP. Patients were randomly assigned to receive Amp/Sulb (9 g every 8h) or COL (3 MIU every 8h) intravenously. Dosage was adjusted according to creatinine clearance. RESULTS: A total of 28 patients were enrolled (15 COL, 13 Amp/Sulb). Resolution of symptoms and signs occurred in 60% (9/15) of the COL group and 61.5% (9/13) of the Amp/Sulb group, improvement in 13.3% (2/15) vs. 15.3% (1/13) and failure in 26.6% (4/15) vs. 23% (3/13), respectively. The difference was not statistically significant. Bacteriologic success was achieved in 66.6% (10/15) vs. 61.5% (8/13) in the COL and Amp/Sulb groups, respectively (p<0.2). Mortality rates (14 days and 28 days) were 15.3% and 30% for the Amp/Sulb and 20% and 33% for the COL group, respectively. Adverse events were 39.6% (including 33% nephrotoxicity) for the COL group and 30.7% (15.3% nephrotoxicity) for the Amp/Sulb group (p=NS). CONCLUSION: Colistin and high-dose ampicillin/sulbactam were comparably safe and effective treatments for critically ill patients with MDR A. baumannii VAP.

The effect of hypoxemic resuscitation from hemorrhagic shock on blood pressure restoration and on oxidative and inflammatory responses.

OBJECTIVE: We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents the late circulatory instability and attenuates the oxidative and inflammatory responses associated with the standard strategy. DESIGN AND SETTING: Prospective, randomized, controlled animal study in an experimental laboratory of a university intensive care unit. SUBJECTS: Thirty-one New Zealand white rabbits weighting 3.1-3.4 kg INTERVENTIONS: Anesthetized animals were subjected to hemorrhagic shock by exsanguinations to a mean arterial pressure of 40 mmHg for 60 min. Resuscitation was performed by reinfusing the shed blood for 30 min under normoxemia (PaO(2) 95-105 mmHg, control group, n=10) or hypoxemia (PaO(2) 35-40 mmHg, hypox-res group, n=10); Ringer's lactate was given from 30 to 60 min to restore arterial pressure within baseline values. A sham group was assigned (n=11). Animals were recorded for 120 min postresuscitation and for further 360 min to assess the early mortality rate. MEASUREMENTS AND RESULTS: Hypoxemic resuscitation compared with normoxemic resuscitation from hemorrhagic shock was associated with (a) a better hemodynamic condition assessed by the gradual restoration of blood pressure, higher urinary output associated with less fluid infusion; (b) lower reactive oxygen species production assessed by the reduced blood geometric mean fluorescence intensity, lower malondialdehyde, and higher ratio of reduced to total glutathione levels; (c) attenuation in the plasma concentrations of IL-1beta, TNF-alpha, and IL-6; and (d) no difference in mortality rate. CONCLUSIONS: Hypoxemic resuscitation from hemorrhagic shock is more efficient than normoxemic in restoring the blood pressure and in attenuating the excessive oxidative and inflammatory responses observed during normoxemic resuscitation.

Acute renal dysfunction in liver diseases.

Renal dysfunction is common in liver diseases, either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. The presence of renal impairment in both groups is a poor prognostic indicator. Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction. Obstructive or post renal dysfunction only rarely complicates liver disease. Hepatorenal syndrome (HRS) is a unique form of renal failure associated with advanced liver disease or cirrhosis, and is characterized by functional renal impairment without significant changes in renal histology. Irrespective of the type of renal failure, renal hypoperfusion is the central pathogenetic mechanism, due either to reduced perfusion pressure or increased renal vascular resistance. Volume expansion, avoidance of precipitating factors and treatment of underlying liver disease constitute the mainstay of therapy to prevent and reverse renal impairment. Splanchnic vasoconstrictor agents, such as terlipressin, along with volume expansion, and early placement of transjugular intrahepatic portosystemic shunt (TIPS) may be effective in improving renal function in HRS. Continuous renal replacement therapy (CRRT) and molecular absorbent recirculating system (MARS) in selected patients may be life saving while awaiting liver transplantation.

High-dose ampicillin-sulbactam as an alternative treatment of late-onset VAP from multidrug-resistant Acinetobacter baumannii.

The increased incidence of multidrug-resistant (MDR) Acinetobacter baumannii ventilator-associated pneumonia in critically ill patients poses a severe therapeutic problem. The aim of this study was to evaluate the efficacy and safety of 2 high-dose treatment regimens of ampicillin-sulbactam (A/S) for MDR Acinetobacter baumannii VAP. We undertook a randomized, prospective trial of critically ill patents with (MDR) Acinetobacter baumannii VAP. Patients were randomly assigned to 1 of 2 treatment regimens of A/S (at a rate 2:1 every 8 h): 1) group A, 18/9 g daily dose (n = 14); and 2) group B, 24/12 g daily dose (n = 13). The duration of therapy was 8+/-2 d for both groups. A total of 27 patients were enrolled in the study. Clinical improvement was seen in 66.7% of the study population in 9/14 (64.3%) of group A patients and 9/13 (69.2%) of group B patients, respectively. Bacteriological success was achieved in 77.8% of the study population (12/14, 85.7% of group A) and in 9/13 (69.2%) of group B patients. The 14-d mortality rate was 25.9% and the all cause 30-d mortality was 48.1%. Both mortality rates did not differ significantly between the 2 groups. No major adverse reactions were recorded. We concluded that clinical and bacteriological results of the study support the use of high-dose regimen of ampicillin-sulbactam for MDR Acinetobacter baumannii VAP.

Purpura fulminans in sepsis.

Sepsis-induced purpura fulminans is a rare but life-threatening disorder, characterized by hemorrhagic infarction of the skin caused by disseminated intravascular coagulation and dermal vascular thrombosis. The pathogenesis is linked to enhanced expression of the natural procoagulants and depletion of the natural anticoagulant proteins particularly protein C. Meningococcal sepsis is the most common cause, followed by pneumococcal sepsis in adults. The syndrome is associated with more than 50% mortality secondary to multiple organ dysfunction syndrome and is accompanied by long-term morbidity. Necrotic lesions usually progress to distal ischemia, and skin grafting and extremities or limb amputation are often required. Early antibiotic administration and intensive care management according to the recommendations of severe sepsis and shock is crucial for patients' survival. Adjuvant therapies against inflammatory and coagulation cascades and augmenting fibrinolysis are still controversial and need further assessment. Among them activated protein C and supplementation therapy have given promising results.

Meningococcal purpura fulminans in a patient with systemic lupus erythematosus: a mimic for catastrophic antiphospholipid antibody syndrome?

Purpura fulminans (PF) is a life-threatening disorder characterized by acute onset of progressive cutaneous hemorrhage, necrosis, and disseminated intravascular coagulation. Acute infectious PF occurs most commonly in the setting of meningococcal sepsis. When PF occurs in the setting of systemic lupus erythematosus (SLE), the catastrophic antiphospholipid antibody syndrome (CAPS) must be ruled out because urgent therapy is required. Plasmapheresis is effective in both cases, but immunosuppression (high-dose corticosteroids plus cyclophosphamide), although beneficial in patients with CAPS, could be harmful in patients with meningococcal PF. The authors report here a patient with SLE who presented to the intensive care unit with meningococcal PF, acute renal failure, and acute respiratory distress syndrome and discuss clinical similarities and laboratory differences from CAPS.

Occidental beriberi and sudden death.

Beriberi, thiamine deficiency, is classified as "dry" (neurologic) or "wet" (cardiovascular) and may be mixed. Deficiency of this vitamin may be nutritional or secondary to alcohol intoxication. In Western societies (occidental beriberi), the disorder is more commonly observed in long-term alcohol abusers. However, it may go undiagnosed because it is relatively uncommon. In some cases (acute cardiovascular beriberi), early treatment with parenteral vitamin B1 is required to prevent the development of low-output state and sudden death. We report a case of occidental beriberi with fatal outcome despite therapy.

Heparin-induced thrombocytopenia with pulmonary embolism and disseminated intravascular coagulation associated with low-molecular-weight heparin.

Heparin-induced thrombocytopenia (HIT) is a severe adverse effect of heparin therapy. Although most cases occur in patients receiving unfractionated heparin, HIT can arise in venous thrombosis prophylaxis with a low-molecular-weight heparin (LMWH). We report an uncommon case of HIT in a postoperative orthopedic patient associated with LMWH (nadroparin), complicated by deep venous thrombosis, pulmonary embolism, and disseminated intravascular coagulation, treated successfully with recombinant hirudin and immunoglobulin therapy.