Marco Fiore

Reactivation of overt and occult hepatitis B infection in various immunosuppressive settings

The aim of the study was to evaluate clinical and virological differences in HBV reactivation between patients with overt and occult HBV infection. Twenty‐three consecutive patients with symptomatic HBV reactivation occurring during or after immunosuppressive therapy were enrolled in a retrospective study: 10 with reactivation of overt HBV infection (overt group) and 13 of occult HBV infection (occult group). Twenty‐one patients were treated with nucleot(s)ide analogues after HBV reactivation. Regimens including rituximab or fludarabine were administered more frequently in the occult group (61% vs. 31%, respectively). HBV reactivation was severe frequently in the overt (40%) and occult groups (38.4%). Patients in the overt group showed higher HBV‐DNA titers (1.1u2009×u2009108u2009±u20091.4u2009×u2009108 vs. 5.1u2009×u2009105u2009±u20096.8u2009×u2009105u2009IU; Pu2009<u20090.005). Seven patients died during HBV reactivation, two in the overt and five in the occult group. Of these seven patients, two remained untreated and five had been treated with Lamivudine; of the 16 patients showing remission of HBV reactivation, four had been treated with Lamivudine, four with Entecavir, two with Telbivudine, and six with Lamivudine plus Adefovir. It is concluded that HBV reactivation is life‐threatening in patients with diseases inhibiting the immune response and/or receiving immunosuppressive drugs. Supportive therapy without antiviral drugs or Lamivudine monotherapy may not be effective for treating patients with HBV reactivation. J. Med. Virol. 83:1909–1916, 2011.

Outpatient parenteral antibiotic therapy for bone and joint infections : An italian multicenter study

Abstract In the early eighties, the advantages of outpatient parenteral antibiotic therapy (OPAT) (reduced costs, no hospitalization trauma in children, no immobilization syndrome in elderly, reduction in nosocomial infections by multiresistant organisms) were identified in the United States, and suitable therapeutic programs were established. Currently, more than 250,000 patients per year are treated according to an OPAT program. In order to understand the different ways of managing OPAT and its results, a National OPAT Registry was set up in 2003 in Italy. Analysis of data concerning osteomyelitis, septic arthritis, prosthetic joint infection and spondylodiskitis, allowed information to be acquired about 239 cases of bone and joint infections, with particular concern to demographics, therapeutic management, clinical response, and possible side effects. Combination therapy was the first-line choice in 66.9% of cases and frequently intravenous antibiotics were combined with oral ones. Teicoplanin (38%) and ceftriaxone (14.7%), whose pharmacokinetic/pharmacodynamic properties permit once-a-day administration, were the two top antibiotics chosen; fluoroquinolones (ciprofloxacin and levofloxacin) were the most frequently utilized oral drugs. Clinical success, as well as patients and doctors satisfaction with the OPAT regimen was high. Side-effects were mild and occurred in 11% of cases. These data confirm that the management of bone and joint infections in an outpatient setting is suitable, effective and safe.

Foot infections in diabetes (DFIs) in the out-patient setting: an Italian multicentre observational survey

Aimsu2003 To conduct a multicentre observational study to describe management of foot infections in diabetes in the out‐patient setting in Italy.

Tolerability and efficacy of anti-HBV nucleos(t)ide analogues in HBV-DNA-positive cirrhotic patients with HBV/HCV dual infection

Summary.u2002 We evaluated tolerability and virological and clinical impact of anti‐Hepatitis B Virus (HBV) nucleos(t)ide analogues in cirrhotic patients with HBV/Hepatitis C Virus (HCV) coinfection. The virological and clinical course of 24 consecutive HBsAg/HBV‐DNA/anti‐HCV‐positive patients with cirrhosis was compared with that of 24 HBsAg/HBV‐DNA‐positive, anti‐HCV‐negative cirrhotic patients, pair‐matched for age (±5u2003years), sex, HBeAg/anti‐HBe status and Child‐Pugh class. Patients in both groups were previously untreated with oral antiviral agents at enrolment and were treated for at least 24u2003months (range 24–54). At the 12th and 18th month of treatment, HBV‐DNA was negative in 21 (87.5%) and 23 (95.8%) patients with hepatitis B and C and in 20 (83.3%) and 22 (91.6%) in patients with isolated HBV; all patients in both groups were HBV‐DNA‐negative at month 24 and at subsequent observations. Treatment was well tolerated by all patients in both groups. At the last observation (for co‐infected patients, median 44u2003months and range 24–54; for mono‐infected patients, median 40u2003months and range 24–54), a deterioration in Child class was observed in eight (47%) of 17 patients in patients with both HBV and HCV who were HCV‐RNA‐positive at baseline, but in none of seven HCV‐RNA‐negative patients in the same group, and in one patient (4.2%) in the mono‐infected patients. Reactivation of HCV infection was relatively infrequent (12.5% of cases) and never associated with a clinical deterioration. Treatment with nucleotides in HBsAg/HBV‐DNA/anti‐HCV‐positive patients with cirrhosis showed a favourable virological effect in all cases, but a favourable clinical result only in the HCV‐RNA‐negative at baseline.

In Vitro Activity of Tigecycline: MICs, MBCs, Time-Kill Curves and Post-Antibiotic Effect

Abstract The minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), time-kill curves, and postantibiotic effect (PAE) of tigecycline, the first in the glycylcycline class of antibiotics, were evaluated. MICs were determined against 749 clinical isolates. Time-kill curves were performed against two isolates each of Enterococcus faecalis, MSSA, and MRSA. The presence of PAE, against the same isolates, was investigated. MIC90s (μg/mL) were the following: Escherichia coli 0.25; Klebsiella spp 0.5; Enterobacter spp 1; Acinetobacter spp. 2; Staphylococcus aureus (MSSA+MRSA) 0.25; CNS (MS+MR) 0.25; vancomycin-susceptible Enterococcus faecalis 0.12. Tigecycline exerted bacteriostatic activity against all the tested isolates, MBC90 values being 32×MIC. Time-kill experiments showed a marked reduction in bacterial growth. A PAE at 1- to 20-fold the MIC was observed against the two enterococcal isolates (1.5-3.2h, range) and the four staphylococci (1.6-3h, range). Our findings confirm the excellent antimicrobial activity of tigecycline, adding in-formation on its bacteriostatic activity vs enterococci and staphylococci, whether methicillin-resistant or -susceptible, and its PAE.

Nosocomial spontaneous bacterial peritonitis: discussing a specific infection treatment algorithm.

To the Editor: Nosocomial spontaneous bacterial peritonitis (N-SBP) is frequently caused by multi drug resistant (MDR) bacteria. Recently Sol a E., Sol e C. and Gin es P. have suggested piperacillin/tazobactam or meropenem ± glycopeptide as initial empirical antibiotic therapy (EAT) (1). The spectrum of causative agents of N-SBP has changed in Europe. Although Gram-negative bacteria were the main infectious agents a few decades ago, and are still reported to be so in the most recent reviews (1), Gram-positive cocci are now predominant. Enterococci are isolated in about a quarter of the cases and these infections appear to be significantly associated with poor patient survival. Moreover, although the global implication of Gram-negative bacteria is declining slightly, the proportion of pathogens that produce extended-spectrum beta-lactamases (ESBL) is increasing: around 40% of isolated organisms are resistant to beta-lactam antibiotics (2, 3). The majority of available data suggest that, regardless of in vitro susceptibility results, it is best to avoid the use of piperacillin/tazobactam for life threatening infections because of ESBL (4). Furthermore, Enterococcus faecium and Methicillin-resistant staphylococci are uniformly resistant to meropenem. Currently, glycopeptides, which for years have been the chief antibiotic for MDR Gram-positive cocci infections, give concerns owing to a high rate of vancomycin-resistant enterococci (VRE), the potential risk of nephrotoxicity and an increase in the mean minimum inhibitory concentration (MIC) of vancomycin in clinical isolates (a phenomenon known as MIC creep), besides when teicoplanin is administered intravenously at 10 mg/kg of body weight, low concentrations are achieved in peritoneal fluid (5). These observations seem to be confirmed by the Randomized Clinical Trial of Piano et al. (2), who demonstrated high efficacy of daptomycin combined to meropenem for the treatment of N-SBP. Daptomycin is a novel lipoptide effective in the treatment of VRE and MDR staphylococci, it is best to use daptomycin in combination therapy: Concomitant beta-lactam increase the antibacterial activity of daptomycin against MDR staphylococci, prevent selection of daptomycin-resistant derivatives and restores daptomycin activity against daptomycin-nonsusceptible VRE. In conclusion, the available data do not suggest to recommend EAT with piperacillin/tazobactam or glycopeptides (1). Based on current evidence, it could be proposed a specific

The possible role of anti-methicillin-resistant Staphylococcus aureus antimicrobial agents in spontaneous bacterial peritonitis

Dear Editor, n nWe read with great interest the case report by Falcone et al. on the treatment of Spontaneous Bacterial Peritonitis (SBP) due to methicillin-resistant Staphylococcus aureus (MRSA) with high vancomycin minimum inhibitory concentration (MIC) value.1 The authors treated a SBP (microbiological results of ascites fluid showed MRSA) in a cirrhotic patient with a documented allergy to tetracycline with daptomycin (6 mg/kg/day) for 12 days. n nTigecycline, a glycylcycline licenced for the treatment of intra-abdominal infections (IAI),2 unlike daptomycin, that is effective against MDR Gram-positive bacteria, including MRSA and vancomycin-resistant enterococci (VRE) was contraindicated because of the documented allergy to tetracyclines. n nThe authors state that the linezolid can not be used in the majority of patients with cirrhosis and bacterial infections because of myelotoxicity and thrombocytopenia. Indeed thrombocytopenia is a long term (over two weeks of therapy) reversible adverse effect;3 however duration of SBP antibiotic treatment is unclear;4 treatment for 5 days has shown success and longer treatment is recommended if blood cultures are positive.5 n nFurthermore, daptomycin is associated with higher all-cause mortality and trend for higher relapse rate than linezolid.6 Daptomycin displays a dose-dependent response against VRE with high-dose daptomycin (10-12 mg/kg/day) producing most bactericidal activity,7 and a daptomycin dosage of 8 mg/kg/day or greater may be safe in patients with complicated gram-positive infections.8 So in other life-threatening setting such as infective endocarditis, patients had successful outcomes with high-dose daptomycin therapy.9 n nFinally, several reports have linked increases in vancomycin MICs to increases in daptomycin MICs and thus high-dose daptomycin should be in place of standard dosing.10,11 n nIn conclusion, according to current evidence the low-dose daptomycin used in the case report does not seem to be the best therapeutic choice for the treatment of gram-positive SBP.

Preemptive therapy of spontaneous fungal peritonitis

tion and published data in AIH patients suggest that prospective studies using anti-CD20 as initial therapy to induce remission in patients with AIH are indicated. These studies will be able to provide safety profile and design tailored protocols for different subtypes of AIH patients, including those with other comorbidities. Initial therapy should allow a rapid, complete remission of liver inflammation with minimal or no side effects to avoid or diminish the evolution to cirrhosis or recover from liver failure; such is not the case with currently administered immunosuppressive drugs.

Community-acquired pneumonia: is it time to shorten the antibiotic treatment?

Evaluation of: Li JZ, Winston LG, Moore DH, Bent S. Efficacy of short-course antibiotic regimens for community-acquired pneumonia: a meta-analysis. Am. J. Med. 120, 783–790 (2007). Guidelines for community-acquired pneumonia (CAP) treatment have been published since 1993. Currently, the guidelines developed under the auspices of the Infectious Diseases Society of America and the American Thoracic Society are used. Empirical antibiotic recommendations reported in the current guidelines have not changed significantly from those reported previously concerning the choice of antibiotics, whereas the treatment duration is generic. Actually, in clinical practice, it seems that patients with mild-to-moderate CAP are overtreated for 7–10 days. The concern regarding adverse drug interactions, drug costs and, especially, increasing antimicrobial resistance have led to attempts to shorten the duration of therapy for CAP.