Over the past several years, the prevalence of human disease caused by nontuberculous mycobacteria (NTM) has increased. Whether the increase in cases is real or whether more cases are being ...recognized remains unclear. Despite a considerable increase in knowledge about NTM infections, they still represent a diagnostic and therapeutic challenge for several reasons: 1) pathogenic isolates may be indistinguishable from contaminant or saprophytic isolates; 2) timely and reliable identification of isolates may depend on proper communication between clinicians and laboratory staff; 3) lack of standardized susceptibility testing makes adoption of tailored therapies unrealistic; and 4) lack of treatment guidelines exposes patients to toxic drugs and disappointing outcomes. Laboratory research and multicenter controlled trials are needed to improve diagnosis and treatment of these infections.
Extrapulmonary tuberculosis (EPTB) accounts for more than 20% of tuberculosis (TB) cases. Xpert MTB/RIF (Xpert) (Cepheid, Sunnyvale, CA, USA) is a fully automated amplification system, for which ...excellent results in the diagnosis of pulmonary TB in highly endemic countries have been recently reported. We aimed to assess the performance of the Xpert system in diagnosing EPTB in a low incidence setting. We investigated with Xpert a large number of consecutive extrapulmonary clinical specimens (1,476, corresponding to 1,068 patients) including both paediatric (494) and adult samples. We found, in comparison with a reference standard consisting of combination of culture and clinical diagnosis of TB, an overall sensitivity and specificity of 81.3% and 99.8% for Xpert, while the sensitivity of microscopy was 48%. For biopsies, urines, pus and cerebrospinal fluids the sensitivity exceeded 85%, while it was slightly under 80% for gastric aspirates. It was, in contrast, lower than 50% for cavitary fluids. High sensitivity and specificity (86.9% and 99.7%, respectively) were also obtained for paediatric specimens. Although the role of culture remains central in the microbiological diagnosis of EPTB, the sensitivity of Xpert in rapidly diagnosing the disease makes it a much better choice compared to smear microscopy. The ability to rule out the disease still remains suboptimal.
We assessed the population pharmacokinetics of high-dose continuous-infusion (HDCI) meropenem in a cohort of patients with
carbapenemase (KPC)-producing
(KPC-Kp) infections. Monte Carlo simulations ...were used to define the permissible HDCI meropenem regimens that could be safely considered for the treatment of KPC-Kp infections due to meropenem-resistant strains. Permissible doses were arbitrarily defined as those associated with a ≤10% to 15% likelihood of meropenem steady-state concentrations (
) of >100 mg/liter. Probabilities of target attainment (PTA) of four incremental pharmacodynamic determinants for meropenem efficacy (100% T
, 100% T
, 100% T
, and 100% T
, where "T
" represents the time during which the plasma concentration of this time-dependent antibacterial agent is maintained above the MIC for the pathogen) in relation to different classes of renal function were calculated. The cumulative fractions of response (CFR) for the permissible HDCI meropenem regimens were calculated against the MIC distribution of the KPC-Kp clinical isolates that were collected routinely at our University Hospital between 2013 and 2016 (
= 169). Ninety-seven meropenem
were included in the analysis. The final model included creatinine clearance (CrCL) as a covariate and explained 94% of the population variability. Monte Carlo simulations based on licensed dosages of up to 6 g/day predicted an acceptable PTA (>80%) of 100% T
against KPC-Kp with a meropenem MIC of ≤32 mg/liter in patients with a CrCL level of <130 ml/min. Dosages of 8 g/day were needed for achieving the same target in patients with CrCL at levels of 130 to 200 ml/min. In dealing with pathogens with a meropenem MIC of 64 mg/liter, HDCI regimens using meropenem at higher than licensed levels should be considered. In these cases, real-time therapeutic drug monitoring could be a useful adjunct for optimized care. The predicted CFR were >75% in all of the classes of renal function.
Candida is an important cause of bloodstream infections (BSI) in nosocomial settings causing significant mortality and morbidity. This study was performed to evaluate contemporary epidemiology, ...species distribution, antifungal susceptibility and outcome of candida BSI in an Italian hospital.
All consecutive patients who developed candidemia at Santa Maria della Misericordia University Hospital (Italy) between January 2009 and June 2014 were enrolled in the study.
A total of 204 episodes of candidemia were identified during the study period with an incidence of 0.79 episodes/1000 admissions. C. albicans was isolated in 60.3% of cases, followed by C. parapsilosis (16.7%), C. glabrata (11.8%) and C. tropicalis (6.4%). Of all Candida BSI, 124 (60.8 %) occurred in patients admitted to IMW, 31/204 (15.2 %) in ICUs, 33/204 (16.2%) in surgical units and 16/204 (7.8%) in Hematology/Oncology wards. Overall, 47% of patients died within 30 days from the onset of candidemia. C. parapsilosis and C. glabrata candidemia were associated with the lowest mortality rate (36%), while patients with C. tropicalis BSI had the highest mortality rate (58.3%). Lower mortality rates were detected in patients receiving therapy within 48 hours from the time of execution of the blood cultures (57,1% vs 38,9%, P < 0.05). At multivariate analysis, steroids treatment (OR = 0.27, p = 0.005) and CVC removal (OR = 3.77, p = 0.014) were independently associated with lower and higher survival probability, respectively. Candidemia in patients with peripherally inserted central catheters (PICC) showed to be associated with higher mortality in comparison with central venous catheters (CVC, Short catheters and Portacath) and no CVC use. For each point increase of APACHE III score, survival probability decreased of 2%. Caspofungin (OR = 3.45, p = 0.015) and Amphothericin B lipid formulation (OR = 15.26, p = 0.033) were independently associated with higher survival probability compared with no treatment.
Purpose
Clinical data on patients with intra-abdominal candidiasis (IAC) is still scarce.
Methods
We collected data from 13 hospitals in Italy, Spain, Brazil, and Greece over a 3-year period ...(2011–2013) including patients from ICU, medical, and surgical wards.
Results
A total of 481 patients were included in the study. Of these, 27 % were hospitalized in ICU. Mean age was 63 years and 57 % of patients were male. IAC mainly consisted of secondary peritonitis (41 %) and abdominal abscesses (30 %); 68 (14 %) cases were also candidemic and 331 (69 %) had concomitant bacterial infections. The most commonly isolated
Candida
species were
C. albicans
(
n
= 308 isolates, 64 %) and
C. glabrata
(
n
= 76, 16 %). Antifungal treatment included echinocandins (64 %), azoles (32 %), and amphotericin B (4 %). Septic shock was documented in 40.5 % of patients. Overall 30-day hospital mortality was 27 % with 38.9 % mortality in ICU. Multivariate logistic regression showed that age (OR 1.05, 95 % CI 1.03–1.07,
P
< 0.001), increments in 1-point APACHE II scores (OR 1.05, 95 % CI 1.01–1.08,
P
= 0.028), secondary peritonitis (OR 1.72, 95 % CI 1.02–2.89,
P
= 0.019), septic shock (OR 3.29, 95 % CI 1.88–5.86,
P
< 0.001), and absence of adequate abdominal source control (OR 3.35, 95 % CI 2.01–5.63,
P
< 0.001) were associated with mortality. In patients with septic shock, absence of source control correlated with mortality rates above 60 % irrespective of administration of an adequate antifungal therapy.
Conclusions
Low percentages of concomitant candidemia and high mortality rates are documented in IAC. In patients presenting with septic shock, source control is fundamental.
is considered to be an emerging fungal pathogen and is related to high mortality rates, persistent candidemia, inconsistencies in susceptibility testing results and misidentification by available ...commercial identification systems. Multidrug-resistant (MDR) and pandrug-resistant (PDR) strains are increasingly detected. In Europe, hospital outbreaks caused by
have been reported in the United Kingdom (UK), Italy and Spain; however, several cases have been sporadically detected in all European countries.
is difficult to control despite enhanced control measures due to its ability to survive for a long time in environments and colonize patients for prolonged periods. An adequate laboratory diagnostic capacity and national surveillance are fundamental to rapidly detect new
cases and to apply the correct measures to circumscribe them and prevent their spread. Our narrative review aims to highlight the primary
outbreaks and case reports that have occurred in Europe.
Summary A decline in the prevalence of tuberculosis in the developed world over the past several years has been accompanied by an increase in the rate of mycobacterial disease caused by ...non-tuberculous mycobacteria. However, it is still unclear whether there is a real increase in prevalence or whether non-tuberculous mycobacterial disease is being recognised more frequently by clinicians in a variety of clinical settings, thus enhancing the competence of microbiologists to detect the more unusual and fastidious mycobacteria. The introduction of liquid media for isolation of mycobacteria coupled with more accurate methods for identification have allowed several new species associated with human disease to be recognised. Despite this progress, several issues related to non-tuberculous mycobacterial infections need to be addressed, including the timely and reliable identification of isolates, standardisation and clinical evaluation of susceptibility testing, and capability to distinguish disease-causing isolates from contaminant or saprophytic species. Treatment regimens for non-tuberculous mycobacterial disease are still largely undefined and outcome remains disappointing despite substantial upgrading in laboratory diagnosis and the availability of new antimicrobials. Treatment success is impaired by the long duration of regimens, side-effects, and drug interactions, which prevent patients from full compliance. We discuss the epidemiological features, clinical syndromes, and developments in the investigation, prevention, and treatment of pulmonary non-tuberculous mycobacterial infections.
We aimed to describe the characteristics of patients with Staphylococcus aureus bacteremia and to evaluate the risk factors associated with early (7-day) and late (30-day) mortality. We performed an ...observational study including all consecutive episodes of Staphylococcus aureus bacteremia diagnosed at two Italian university hospitals during 2010-2014. A total of 337 patients were included. Mean age was 69 years (range, 57-78) and 65% were males. Methicillin-resistant S. aureus (MRSA) was identified in 132/337 (39%)cases. Overall 7- and 30-day mortality were 13% and 26%, respectively. Early mortality was associated with increased Charlson scores (OR 1.3, 95% CI 1.1-1.5), MRSA bacteremia (OR 3.2, 95% CI 1.4-8.1), presentation with septic shock (OR 13.5, 95% CI 5.4-36.4), and occurrence of endocarditis (OR 4.5, 95%CI 1.4-14.6). Similar risk factors were identified for late mortality, including increased Charlson scores (OR 1.2, 95% CI 1.1-1.4), MRSA bacteremia (OR 2.1, 95% CI 1.2-3.9), presentation with septic shock (OR 4, 95%CI 1.7-9.7), occurrence of endocarditis (OR 3.8, 95% CI 1.4-10.2) as well as Child C cirrhosis (OR 3.9, 95% CI 1.1-14.4) and primary bacteremia (OR 2.5, 95%CI 1.3-5). Infectious disease consultation resulted in better outcomes both at 7 (OR 0.1, 95% CI 0.05-0.4) and at 30 days (OR 0.4, 95% CI 0.2-0.7). In conclusion, our study highlighted high rates of MRSA infection in nosocomial Staphylococcus aureus bacteremia. Multiple comorbidities, disease severity and methicillin-resistance are key factors for early and late mortality in this group. In patients with Staphylococcus aureus bacteremia, infectious disease consultation remains a valuable tool to improve clinical outcome.
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