Francesca Leonardis

Acinetobacter baumannii in intensive care unit: A novel system to study clonal relationship among the isolates

BackgroundThe nosocomial infections surveillance system must be strongly effective especially in highly critic areas, such as Intensive Care Units (ICU). These areas are frequently an epidemiological epicentre for transmission of multi-resistant pathogens, like Acinetobacter baumannii. As an epidemic outbreak occurs it is very important to confirm or exclude the genetic relationship among the isolates in a short time. There are several molecular typing systems used with this aim. The Repetitive sequence-based PCR (REP-PCR) has been recognized as an effective method and it was recently adapted to an automated format known as the DiversiLab system.MethodsIn the present study we have evaluated the combination of a newly introduced software package for the control of hospital infection (VIGI@ct) with the DiversiLab system. In order to evaluate the reliability of the DiversiLab its results were also compared with those obtained using f-AFLP.ResultsThe combination of VIGI@ct and DiversiLab enabled an earlier identification of an A. baumannii epidemic cluster, through the confirmation of the genetic relationship among the isolates. This cluster regards 56 multi-drug-resistant A. baumannii isolates from several specimens collected from 13 different patients admitted to the ICU in a ten month period. The A. baumannii isolates were clonally related being their similarity included between 97 and 100%. The results of the DiversiLab were confirmed by f-AFLP analysis.ConclusionThe early identification of the outbreak has led to the prompt application of operative procedures and precautions to avoid the spread of pathogen. To date, 6 months after the last A. baumannii isolate, no other related case has been identified.

Emergence of KPC-producing Klebsiella pneumoniae in Italy

BackgroundThe emergence of KPC-producing K. pneumoniae has now become a global concern. KPC beta-lactamases are plasmid-borne and, like extended spectrum beta lactamases (ESBLs), can accumulate and transfer resistance determinants to other classes of antibiotics. Therefore, infection control guidelines on early identification and control of the spread of organisms carrying these resistant determinants are needed.FindingsKlebsiella pneumoniae carbapenemase (KPC) was detected in two isolates of carbapenem-resistant K. pneumoniae obtained from patients at an Italian teaching hospital. The first strain was isolated from a culture drawn from a central venous device (CVC) in a patient with Crohns disease who was admitted to a gastroenterology ward. The second was isolated from a urine sample collected from an indwelling urinary catheter in an intensive care unit (ICU) patient with a subdural haematoma. The patients had not travelled abroad. Both isolates were resistant to all β-lactams and were susceptible to imipenem and meropenem but resistant to ertapenem. Isolates also showed resistance to other classes of non-β-lactam antibiotics, such as quinolones, aminoglycosides (with the exception for amikacin), trimethoprim-sulfamethoxazole (TMP-SMX) and nitrofurantoin. They were determined to contain the plasmid encoding the carbapenemase gene bla-KPC and were also positive in the Hodge test.ConclusionsThis is the second report of KPC-producing isolates in Italy, but the first concerning KPC type 2 gene, and it may have important implications for controlling the transmission of microorganisms resistant to antibiotics.

Transdermal Buprenorphine in Non-Oncological Moderate-to-Severe Chronic Pain

AbstractBackground: Musculoskeletal pathologies are among the most frequent causes of long-term non-oncological severe pain and consequent physical impairment. Aims of pharmacological and physical therapy are to reduce pain, promote functional recovery and improve overall quality of life. Pharmacological therapy may include the use of opioids.n Objective: To evaluate the efficacy and tolerability of transdermal buprenorphine (TDS) in the long-term management of non-oncological, chronic, moderate-to-severe musculoskeletal pain.n Study Design: An open-label, prospective, single-centre, 6-month study.n Setting: A ‘real world’ outpatient setting.n Patients: Adult patients with chronic moderate-to-severe musculoskeletal pain were enrolled consecutively.n Intervention: Patients initially received buprenorphine TDS 11.7 µg/h (onethird of 35 µg/h patch) every 72 hours. If required, patients could be uptitrated to 17.5 µg/h (one-half of 35µg/h patch), 23.4 µg/h (two-thirds of 35 µg/h patch) or 35 µg/h. Concomitant antiemetics were allowed.n Main Outcome Measures: The primary endpoint was percentage mean reduction in static and dynamic pain visual analogue scale (VAS) scores at study end (10 being worst pain, 0 being no pain). Quality of life and tolerability were also assessed.n Results: We enrolled 146 patients aged 41–94 years; their baseline mean± SD static and dynamic pain VAS scores were 6.87±1.89 and 7.70 ± 1.74, respectively. Buprenorphine TDS initial dosages were 11.7 µg/h (n=139), 17.5 µg/h (n = 4), 23.4 µg/h (n= 1) and 35 µg/h (n = 2). At 6 months, 89 patients were under treatment; 11% (n=10) were receiving 11.7µg/h, 30% (n = 27) 17.5 µg/h, 6% (n = 5) 23.4 µg/h and 53% (n = 47) 35µg/h. Patients achieved a nonsignificant reduction in pain at rest and in movement; mean ± SD static and dynamic pain VAS scores decreased to 1.56 ± 2.05 and 3.54 ± 2.02, respectively. The quality of life improved as shown by significant (p< 0.01) increases from baseline in all items relating to physical and mental health on the Short-Form 36 health survey. Patients experienced recovery of daily and social activities according to the significant (p<0.01) increase in Karnofsky Performance Status sub-item scores. Twenty-three patients discontinued treatment because of adverse events, which were mainly gastrointestinal or CNS-related.n Conclusions: Low-dose buprenorphine TDS had good analgesic efficacy, and quality of life improved as early as 1 month after treatment initiation. Our results suggest that buprenorphine TDS is a well tolerated long-term analgesic for patients experiencing chronic musculoskeletal pain of moderateto-severe intensity.

Clinical predictors and microbiology of ventilator-associated pneumonia in the intensive care unit: a retrospective analysis in six Italian hospitals

The purpose of this study was to assess the main clinical predictors and microbiological features of ventilator-associated pneumonia (VAP) in the Intensive Care Unit (ICU) environment. This work is a retrospective analysis over one year from September 2010 to September 2011. Patients’ risk factors, causes of admission, comorbidities and respiratory specimens collected in six Italian ICUs were reviewed. Incidence and case fatality rate of VAP were evaluated. After stratification for VAP development, univariate and multivariate analyses were performed to assess the impact of patients’ conditions on the onset of this infection. A total of 1,647 ICU patients (pts) were considered. Overall, 115 patients (6.9xa0%) experienced at least one episode of VAP. The incidence rate for VAP was 5.82/1,000 pts-days, with a case fatality rate of 44.3xa0%. Multivariate analysis showed that admission for neurological disorders (aIRR 4.12, CI 1.24–13.68, pu2009=u20090.02) and emergency referral to ICU from other hospitals (aIRR 2.11, CI 1.03–4.31, pu2009=u20090.04) were associated with higher risk of VAP, whereas a tendency to a higher risk of infection was detected for admission due to respiratory disease, cardiac disease, trauma and for having obesity or renal failure. A total of 372 microbiological isolates from respiratory specimens were collected in VAP patients. The most common species were Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, showing high resistance rates to carbapenems. Neurological disorders and emergency referral at the admission into the ICU are significantly associated with the onset of VAP. A high incidence of multi-drug resistant Gram-xa0species was detected in the respiratory specimens.

Microbiologic characteristics and predictors of mortality in bloodstream infections in intensive care unit patients: A 1-year, large, prospective surveillance study in 5 Italian hospitals

BACKGROUNDnBloodstream infections (BSIs) from multidrug-resistant (MDR) bacteria cause morbidity and mortality in intensive care unit (ICU) patients worldwide. This study investigated the incidence of BSIs in 5 adult general ICUs in Rome, Italy, and evaluated the mortality rate and risk factors associated with these infections.nnnMETHODSnOver a 12-month period, 1,318 patients were enrolled. Demographic characteristics, Simplified Acute Physiology Score II (SAPS II), comorbidities, and BSI isolate data were collected. After stratification for the outcome, statistical analysis was performed to assess the impact of patient risk factors on in-hospital mortality.nnnRESULTSnThere were 324 BSIs in 175 patients recorded, with an in-hospital mortality rate of 46%. Univariate analysis revealed that SAPS II, cardiac comorbidity, and Klebsiella pneumoniae BSI were significantly associated with a higher risk of death. Having a K pneumoniae BSI and cardiac illness at admission were both confirmed to be associated with death by multivariate analysis (Pxa0=xa0.0162 and Pxa0=xa0.0158, respectively). Most of the K pneumoniae isolates showed high resistance rates to carbapenems.nnnCONCLUSIONnBSIs caused by K pneumoniae and cardiovascular comorbidity in ICU patients are associated with a higher risk of death. Thorough surveillance for MDR pathogens and stratification of the patients risk on admission into the ICU are key to improving the outcomes of these infections.

Upregulation of the inhibitory receptor ILT4 in monocytes from septic patients.

Sepsis-induced immune dysfunction is a complex phenomenon that involves both innate and adaptive responses. Upregulation of the inhibitor receptor named immunoglobulin like transcript 4 (ILT4) is crucial to the tolerogenic function of monocytes. Here, ILT4 expression, endotoxin-induced IL-12 and IL-10 production and CD86 expression were investigated in circulating monocytes from 16 patients with severe sepsis and 16 age and sex matched controls. We found that monocytes from patients with severe sepsis express significantly higher levels of ILT4 than monocytes from controls. Upregulation of ILT4 expression appeared to be induced by soluble factors present in the serum of septic patients and directly correlated with the degree of organ dysfunction. ILT4(+) monocytes from septic patients also displayed an alteration in the cytokine response to endotoxin stimulation characterized by reduced IL-12 production and increased IL-10 production, and a reduced expression of the costimulatory molecule CD86. In conclusion, the increased ILT4 expression and IL-10 production and the decreased CD86 expression and IL-12 production indicate that during sepsis monocytes undergo substantial modulation of the surface and cytokine phenotype. These phenotypic changes may interfere with the antigen presenting cell activity of monocytes, which may contribute to the impairment of adaptive immune responses that takes place during sepsis.

Development of collateral veins as a favorable prognostic factor for complete recovery in cerebral venous thrombosis due to Tribulus terrestris

Cerebral venous thrombosis (CVT) is a relatively uncommon but serious neurologic disorder. It usually occurs in young people and is often associated with multiple prothrombotic risk factors. We describe the case of a 37-year-old healthy man presented to our attention because of cephalgia, nausea, vomit, and a partial motor seizure followed by psychomotor agitation and coma. Urgent brain computed tomography revealed sigmoid sinus thrombosis extending to superior sagittal sinus and cortical veins. Then we performed brain magnetic resonance imaging (MRI) with venography showing, on fluid attenuated inversion recovery (FLAIR) sequences, a hyperintense lesion in the right parietal cortex. MR angiography confirmed cerebral venous thrombosis (see Fig. 1). Complete screening for prothrombotic risk factors was normal. Anticoagulation and diuretic treatments were started and patient was sedated and intubated. Ten days after admission, the patient became progressively alert and intubation was withdrawn. The repeated brain MRI showed the disappearance of the cortical lesion previously evident in FLAIR scans and venography sequences marked the development of many collateral veins (see Fig. 1). At that time, the patient could refer about assumption of Tribulus terrestris (TT) 1000 mg a day started onemonth before hospital admission. We describe the case of a CVT occurring after intake of a TT supplement. TT is a complement of supplements available over the counter and widely used with several indications, such as physical activity (1). However, it is known to be a testosterone booster (1). In fact, TT is also used as a symptomatic treatment for erectile dysfunction (1). For its characteristics, it is targeted at physically active men, including male athletes (1). On this basis, taking into account that testosterone therapy has been strongly associated with thrombotic events (2), we postulated that TT supplements caused CVT in our patient, as no other prothrombotic risk factors were found. Moreover, our patient showed, in concomitance with the improvement of the neurological status, the development of many collateral veins, which seems to support venous drain by passing the cerebral thrombosis, thus causing the restoration of the cerebral hemodynamic status facilitating the clinical recovery. In conclusion, this report would suggest the possibility of serious thrombotic events associated with TT therapy. Moreover, we would one again underline that development of collateral veins could be a marker of favorable outcome in CVT patients.

Non-convulsive status epilepticus in a patient with carbon-monoxide poisoning treated with hyperbaric oxygen therapy.

The presentation of carbon monoxide poisoning is non-specific and highly variable. Hyperbaric oxygen therapy is used for the treatment of this condition. Various reports show the occurrence of self-limiting seizures after carbon monoxide poisoning and as a consequence of hyperbaric oxygen therapy. Contrary to the seizures, status epilepticus has been rarely observed in these conditions. The exact pathophysiology underlying seizures and status epilepticus associated with carbon monoxide poisoning and hyperbaric oxygen therapy is not really clear, and some elements appear to be common to both conditions. We describe a case of non-convulsive status epilepticus in a patient with carbon monoxide poisoning treated with hyperbaric oxygen therapy. The mechanism, MRI findings and implications are discussed.