Triple combination therapy with high-dose ampicillin/sulbactam, high-dose tigecycline and colistin in the treatment of ventilator-associated pneumonia caused by pan-drug resistant Acinetobacter baumannii: a case series study.

Acinetobacter baumannii has evolved in recent decades as a major problem in carbapenem-resistant gram-negative nosocomial infections, associated with high mortality rates especially in intensive care units (ICUs). Recent reports highlight the increasing prevalence of resistance to colistin, a last resort therapeutic option for carbapenem-resistant A. baumannii. We retrospectively evaluated the potential efficacy, in terms of clinical and microbiological cure and mortality, of a combination of intravenous colistin and high-dose ampicillin/sulbactam and high-dose tigecycline, concurrently administered with inhaled colistin, in 10 ICU patients with ventilator-associated pneumonia (VAP) caused by carbapenem- and colistin-resistant A. baumannii strains, with high tigecycline MICs > 2µg/mL. Nine patients (90%) exhibited a successful clinical outcome, accompanied by microbiological eradication in seven of them. All clinically cured patients survived at 14 and 28 days. Acute kidney injury (AKI) was observed in one patient. In view of the increasing prevalence of pan-drug resistant A. baumannii infections in ICUs, its associated high rates of mortality and the lack of effective treatment options, we feel that there is an emerging need for our results to be further validated in larger prospective studies.

Efficacy of Interferon A-2b monotherapy in Β-thalassemics with chronic hepatitis C.

BACKGROUND & AIMS: Monotherapy with standard or pegylated interferon (PegIFN) remains the first-line treatment for HCV infection in patients with thalassemia major (ßTM), although its long-term impact is still unknown. We aimed to assess the efficacy of IFN-a2b/PegIFN-a2b (one or multiple treatment sessions) and the predictors for sustained virological response (SVR) in HCV-infected ßTM patients. METHODS: Between 11/1992 and 12/2013 [median follow-up: 165.5 months (8-237)], 48 ßTM HCV-infected patients [19 males, median age: 22 years (12-45)], received IFN-a2b (n=34) or PegIFN-a2b (n=14). Twenty-three patients (47.9%) had a previous splenectomy; 13/40 (32.5%) patients had Ishak stage >/=4 and 21/40 (52.5%) had siderosis grade 3-4. HCV-genotype was available in 36 patients (genotype 1: 47.2%, 2: 5.6%, 3: 25%, and 4: 22%). IL28B genotype was determined in 37 patients by means of in-house real-time PCR (CC: 27%, CT: 62.2%, TT: 10.8%). RESULTS: Totally, 15/48 (31.3%) achieved SVR following the first treatment and 18/48 (37.5%) after multiple courses. Splenectomy (p=0.01) and fibrosis grade >/=4 (p<0.05) were negative predictors for SVR (first course), whereas splenectomy (p<0.05) and age >18 (p<0.02) for SVR after multiple courses. In HCV-genotype 1/4 (n=25), none of the patients with CT or TT IL28B genotype achieved SVR compared to 50% of the CC patients (p=0.004). CONCLUSIONS: Interferon is an effective therapeutic option in HCV-infected ßTM patients. IL28B genotype was a strong predictor for SVR, together with splenectomy, age and fibrosis.

Hepatitis C in patients with ß-thalassemia major. A single-centre experience.

Chronic hepatitis C (CHC) and iron overload are the main causes of liver disease in ß-thalassemia major (ßTM). There is limited data regarding the course of CHC in this population. All patients (n=144) from the thalassemia centre of the University Hospital of Patras were evaluated (January 1981 to June 2012). Patients were classified into group A (n=57), which consisted of patients with CHC, who either had received antiviral treatment (n=49) or not (n=8), and group B which included 87 patients without CHC. Nineteen patients died during follow-up (median: 257.5 months (1-355)). Survival rates were 84.2 % and 88.5 % for group A and B, respectively. The causes of death were heart failure (63.2 %), accident (10.5 %), sepsis (5.3 %), liver failure (5.3 %), hepatocellular carcinoma (HCC) (5.3 %), non-Hodgkin lymphoma (5.3 %) and multiorgan failure (5.3 %). There were no differences in total survival between the two groups (p=0.524). In the multivariate analysis, survival was neither correlated with CHC (p=ns), nor with anti-HCV treatment (p=ns), whereas independent negative predictors were presence of heart failure (p<0.001), presence of malignancy other than HCC (p=0.001) and non-adherence to chelation treatment (p=0.013). Predictive factors for the development of cirrhosis were: CHC (p<0.001), age>35 years (p=0.007), siderosis grade 3/4 (p=0.029) and splenectomy (p=0.001); however, multivariately, only siderosis grade 3/4 was found to be significant (p=0.049). In this study, survival of patients with ßTM was mainly associated with heart failure, presence of malignancy other than HCC and non-adherence to chelation treatment, rather than with liver disease. Multicentre studies need to be designed to define more accurately the indications of antiviral treatment in this population.