Giampaolo Corti

Acute viral hepatitis increases liver stiffness values measured by transient elastography

Liver tissue alterations other than fibrosis may have an impact on liver stiffness measurement. In this study we evaluated 18 patients without a previous clinical history of liver disease, consecutively admitted for acute viral hepatitis. In each patient, aminotransferase determination and liver stiffness measurement were performed on the same study day, at 3 different points: (1) peak increase in aminotransferase; (2) aminotransferase 50% or less of the peak; (3) aminotransferase levels ≤2× the upper limit of normal. In all patients, the degree of liver stiffness at the time of the peak increase in aminotransferases exceeded the cutoff values proposed for the prediction of significant fibrosis or cirrhosis. A progressive significant reduction in liver stiffness values was observed (P < 0.0001) in the follow‐up period in parallel with the reduction of aminotransferase levels (P < 0.0001). Moreover, a statistically significant, positive correlation between aminotransferases and liver stiffness measurement (LSM) at the onset of acute viral hepatitis was found (r = 0.53, P = 0.02 and r = 0.51, P = 0.03 for alanine aminotransferase and aspartate aminotransferase, respectively). In conclusion, the extent of necroinflammatory activity needs to be carefully considered in future studies aimed at further validating transient elastography, particularly in patients with absent or low‐stage liver fibrosis (in other words, F0‐F2 METAVIR). LSM does not represent a reliable instrument to detect the presence of advanced fibrosis and cirrhosis in patients presenting with a clinical picture of acute hepatitis. (HEPATOLOGY 2007.)

Reliability of transient elastography for the diagnosis of advanced fibrosis in chronic hepatitis C

Background: Transient elastography (TE) has received increasing attention as a means to evaluate disease progression in patients with chronic liver disease. Aim: To assess the value of TE for predicting the stage of fibrosis. Methods: Liver biopsy and TE were performed in 150 consecutive patients with chronic hepatitis C-related hepatitis (92 men and 58 women, age 50.6 (SD 12.5) years on the same day. Necro-inflammatory activity and the degree of steatosis at biopsy were also evaluated. Results: The areas under the curve for the prediction of significant fibrosis (⩾F2), advanced fibrosis (⩾F3) or cirrhosis were 0.91, 0.99 and 0.98, respectively. Calculation of multilevel likelihood ratios showed that values of TE <6 or ⩾12, <9 or ⩾12, and <12 or ⩾18, clearly indicated the absence or presence of significant fibrosis, advanced fibrosis, and cirrhosis, respectively. Intermediate values could not be reliably associated with the absence or presence of the target condition. The presence of inflammation significantly affected TE measurements in patients who did not have cirrhosis (p<0.0001), even after adjusting for the stage of fibrosis. Importantly, TE measurements were not influenced by the degree of steatosis. Conclusions: TE is more suitable for the identification of patients with advanced fibrosis than of those with cirrhosis or significant fibrosis. In patients in whom likelihood ratios are not optimal and do not provide a reliable indication of the disease stage, liver biopsy should be considered when clinically indicated. Necro-inflammatory activity, but not steatosis, strongly and independently influences TE measurement in patients who do not have cirrhosis.

Antibiotic Usage and Risk of Colonization and Infection with Antibiotic-Resistant Bacteria: a Hospital Population-Based Study

ABSTRACT Accurate assessment of risk factors for nosocomial acquisition of colonization by antibiotic-resistant bacteria (ARB) is often confounded by scarce data on antibiotic use. A 12-month, nested, multicenter cohort study was conducted. Target ARB were methicillin (meticillin)-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and ciprofloxacin-resistant Pseudomonas aeruginosa (CR-PA). Nares and rectal swabs were obtained before and after starting antibiotics. Pulsed-field gel electrophoresis was done to define genetic relatedness of the strains. Primary outcomes were (i) the mean time, in days, for acquisition of target ARB colonization in patients previously not colonized; (ii) the rate of acquisition per 1,000 antibiotic-days according to different classes of antibiotics; (iii) the rate of infection caused by the same bacteria as those previously isolated in screening samples; and (iv) the risk factors for ARB acquisition. In total, 6,245 swabs from 864 inpatients were processed. The rate of acquisition was 3%, 2%, and 1% for MRSA, VRE, and CR-PA, respectively. The rate of acquisition of ARB per 1,000 antibiotic-days was 14 for carbapenems, 9 for glycopeptides, and 6 for broad-spectrum cephalosporins and quinolones. The highest rates of acquisition were observed for carbapenems in dialyzed and diabetic patients. Four risk factors were independently associated with acquisition of target ARB: use of carbapenems, age of >70 years, hospitalization for >16 days, and human immunodeficiency virus infection. During the 30-day follow-up, 4 among 42 patients newly colonized by ARB (9%) suffered from an infection due to the same bacteria as those isolated in a previous screening sample. Colonizing and infecting strains from single patients were genotypically identical. Identifying ARB colonization early during antibiotic therapy could target a high-risk hospitalized population that may benefit from intervention to decrease the risk of subsequent nosocomial infections.

ANTISTAPHYLOCOCCAL (MSSA, MRSA, MSSE, MRSE) ANTIBIOTICS

S. aureus and coagulase-negative staphylococci such as S. epidermidis are important causes of infection of the bloodstream, cardiac valves, implanted devices, and skin, with repercussions on mortality and increased economic costs. Treatment of staphylococcal infections is made difficult by the increasing emergence of resistance to beta-lactams and other antimicrobials, including reduced susceptibility to glycopeptides. Penicillin must be used for infrequent penicillin-susceptible isolates, oxacillin and nafcillin are to be considered the major option for penicillin-resistant staphylococci, and glycopeptides are the drugs of choice for infections caused by methicillin-resistant strains. Co-trimoxazole, lincosamides, macrolides, tetracyclines, and fluoroquinolones are alternative agents, primarily in subjects allergic to beta-lactams. Newly introduced or experimental drugs, such as streptogramins (quinupristin-dalfopristin), oxazolidinones (linezolid), carbapenems (LY 333328), everninomicins (SCH 27899), and derivatives of tetracyclines (glycylcyclines), could be useful for therapy of infections caused by multiresistant staphylococci.

Urosepsis in the critical care unit.

Critical care unit patients show a higher risk of developing a bloodstream infection than ward patients. The urinary tract is the main source of hospital-acquired secondary bloodstream infection. Nosocomial urinary tract infection is promoted by bladder catheterization in the vast majority of cases. Aerobic gram-negative bacilli are the prevalent agents of bloodstream infection secondary to a nosocomial urinary tract infection. Sepsis and septic shock are severe complications of these infections in the critical care patient. Management of patients with a septic process of urinary source calls for the combination of adequate life-supporting care, an appropriate antibiotic therapy, and innovative adjunctive measures. Accurate catheter care is the best measure to adopt for the prevention of urosepsis.

Longitudinal assessment of liver stiffness in patients undergoing antiviral treatment for hepatitis C

BACKGROUND Liver stiffness has been suggested as a parameter of fibrosis progression/regression in hepatitis C virus (HCV) patients. AIM To evaluate stiffness before and after peginterferon-ribavirin treatment. METHODS Stiffness was prospectively measured in 74 HCV patients, 32 genotypes 1/4 (43.25%) and 42 genotypes 2/3 (56.75%), before, at end of treatment, and after 3 years of follow-up (49 patients). On the same study day, 21 patients underwent liver biopsy. RESULTS In 55 patients with sustained virological response (74.32%), liver stiffness decreased significantly at end of therapy (6.8±4.9kPa) vs. baseline (9.5±6.9kPa, p=0.04). The decrease vs. baseline was maintained in 30 sustained virological response patients after 3 years follow-up (6.8±4.6kPa vs. 10.8±8.5kPa, p=0.0141). No difference was found at end of treatment vs. baseline (10.1±4.7kPa vs. 9.7±4.2kPa, p=0.825) and after 3 years of follow-up vs. baseline (10.2±3.4kPa vs. 9.7±4.2kPa, p=0.765) in null responders. Similar results were found in relapsers at end of treatment vs. baseline (13.7±7.7kPa vs. 15.2±8.2kPa, p=0.74), and after 3 years of follow-up vs. baseline (16.9±10.0kPa vs. 15.2±8.2kPa, p=0.734). Pre-treatment stiffness >12kPa was significantly associated with no SVR (p<0.025), RR=2.44 (95%C.I. 1.17-5.07). CONCLUSION Liver stiffness may be useful to assess long-term antiviral treatment response.

INFECTIONS IN MULTIPLE MYELOMA

Multiple myeloma is a relatively rare but severe hematologic malignancy. Marked depression in production of normal immunoglobulins, mild neutropenia, and alkylant/steroid therapy or BMT/SCT all produce major suppression of the immune system in the totality of patients. Recurrent bacterial, fungal, and viral infections are an important cause of morbidity and the most common cause of death in these subjects. Prompt diagnosis and appropriate anti-infective chemotherapy are essential in order to reduce the risk of mortality.

Clinical and microbiologic efficacy and safety profile of linezolid, a new oxazolidinone antibiotic

Gram-positive cocci are important causes of infection both in the community and in the hospital, with repercussions on mortality and increased economic costs. Treatment of these infections is made difficult by the increasing emergence of multi-resistant organisms, primarily among Gram-positive cocci, such as vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci, and penicillin-resistant pneumococci. Linezolid, a member of the new class of synthetic antimicrobials named oxazolidinones, has several favourable characteristics including high activity against multiresistant Gram-positive cocci. In a number of clinical trials, linezolid showed good clinical and microbiologic efficacy in the therapy of infections caused by these organisms. It can be considered a valid option for treating both community- and hospital-acquired infections due to multiresistant Gram-positive cocci.

Post-traumatic infection of the lower limb caused by rare Enterobacteriaceae and mucorales in a young healthy male.

Enterobacter amnigenus and Leclercia adecarboxylata are gram-negative aerobic bacilli of the family Enterobacteriaceae that have been isolated from water and, rarely, from various clinical specimens. Absidia is a filamentous fungus of the class Zygomycetes that is ubiquitous in nature and can cause infection, primarily in immunocompromised hosts. Here, we describe an infection of the left lower limb caused by E. amnigenus and L. adecarboxylata with subsequent isolation of Absidia spp. in a patient with multiple traumatic injuries after a major motor vehicle accident. The severity of the clinical picture made amputation necessary, despite aggressive anti-infective therapy with both antibacterial and antifungal agents. Prompt diagnosis and management are mandatory in order to minimize morbidity and even mortality, and reduce the social and economic cost.

Which prophylactic regimen for which surgical procedure

For optimal prevention of infection subsequent to a surgical intervention, it is necessary to follow a series of general principles, including the classification of the type of surgical intervention, the characteristics of the antibiotic used, and the route and the time of its administration. Moreover, with reference to the different types of surgery, other factors assume importance: the etiology of the infection and the ability of the antibiotic to achieve adequate levels in the tissues at the beginning of the infective process. In general abdominal, biliary, and obstetric-gynecologic surgery, which covers many clean-contaminated and contaminated interventions for which antibiotic prophylaxis has been shown to be the most effective, the etiology is often mixed (aerobic and anaerobic flora) with a predominance of gram-negative microorganisms. Thus, an appropriate prophylactic regimen must consider a third-generation cephalosporin, such as cefotaxime, that is effective against most gram-negative bacteria, in particular against Klebsiella pneumoniae. Acylureido penicillins can also be used because of their activity against enterococci, gram-positive microorganisms that are also causes of infection in this area of surgical intervention. Combining an antimicrobial such as clindamycin or metronidazole, which are particularly active against anaerobes, may be recommended as well. In urologic surgery, most infections are caused by Enterobacteriaceae; in addition to the antimicrobial spectrum, the ability of the antibiotic to concentrate adequately in the urine and renal tissue must also be considered. Beta-lactam antibiotics are the agents of choice, in particular, third-generation cephalosporins, aztreonam, and acylureido penicillins. In cardiac, orthopedic, and partially in neurologic surgery, where most infections are due to gram-positive bacteria (primarily methicillin-resistant staphylococci), antibiotic prophylaxis should include a glycopeptide agent (teicoplanin, vancomycin). In the field of surgical prophylaxis, more experience has been accumulated with cefotaxime, used as a short-course regimen or as a convenient single dose, than with any other newer cephalosporin. Cefotaximes broad spectrum of action provides coverage against most potential pathogens and, when used as a single dose, is both convenient and cost-effective.