European Journal of Clinical Microbiology Infectious Diseases

Nabarro, L.; Veeraraghavan, B.

doi: 10.1007/s10096-015-2486-7pmid: 26363636

Carbapenem-resistant Enterobacteriaceae (CRE) are associated with a high mortality rate and are an increasing problem worldwide. In this mini-review, we consider the growing number of observational studies in favour of combination therapy but highlight the absence of randomised control trials. We discuss the importance of data on minimum inhibitory concentrations (MICs), both for surveillance and for individual patient management. We examine the issues surrounding the use of carbapenems, polymyxins and tigecycline in the treatment of CRE. When and how should we be using carbapenems? Which polymyxin is best? Is tigecycline much maligned? Further studies are urgently needed to validate drug combinations, doses and ratios to maximise efficacy whilst reducing drug exposure and adverse effects.

Trifan, A.; Stoica, O.; Stanciu, C.; Cojocariu, C.; Singeap, A.-M.; Girleanu, I.; Miftode, E.

doi: 10.1007/s10096-015-2501-zpmid: 26440041

Over the past two decades, there has been a dramatic worldwide increase in both the incidence and severity of Clostridium difficile infection (CDI). Paralleling the increased incidence of CDI in the general population, there has been increased interest in CDI among patients with liver disease, particularly in those with liver cirrhosis and post liver transplantation. MEDLINE and several other electronic databases from January 1995 to December 2014 were searched in order to identify potentially relevant literature. Patients with cirrhosis and liver transplant recipients are at high risk for the development CDI because of antibiotics and proton pump inhibitors use, frequent and prolonged hospitalization, immunosuppressant therapy, and multiple comorbidities. Enzyme immunoassay to detect C. difficile toxins A and B in stool remains the most widely used test for CDI diagnosis, although, more recently, polymerase chain reaction (PCR)-based assays have become the preferred diagnostic test in many laboratories. Metronidazole and vancomycin, given orally, have proved to be effective in the treatment of CDI. Both cirrhotic patients and liver transplant recipients with CDI have longer length of hospital stay, increased mortality, and higher healthcare costs than those without CDI. A rapid diagnosis and adequate therapy of CDI are of paramount importance to improve liver disease patients’ outcome. The aim of this review is to provide up-to-date information on the epidemiology, risk factors, pathogenesis, treatment, and outcomes in liver disease patients with CDI.

Prehn, J.; Vandenbroucke-Grauls, C.; Beurden, Y.; Houdt, R.; Vainio, S.; Ang, C.

doi: 10.1007/s10096-015-2484-9pmid: 26377204

Current international guidelines lack definite conclusions regarding repeat stool sampling for the detection of toxigenic Clostridium difficile. We assessed the value of repeat sampling and compared the diagnostic yield in an epidemic to a non-epidemic setting. Consecutive fecal samples obtained during two time frames were analyzed using direct stool immunoassay toxin testing (enzyme immunoassay [EIA]), direct stool real-time PCR toxin gene testing, and toxigenic culture. Samples collected within 7 days of the initial sample were considered repeat tests. In the epidemic setting 989 patients were analyzed, and in the non-epidemic setting 1,015. In the epidemic setting 204 patients had two or more specimens included for analysis and in the non-epidemic setting 287 patients. In the epidemic setting 136 samples yielded a positive results, either by EIA or toxigenic culture; of these, 108 were positive according to EIA and 123 according to toxigenic culture. In the first test round 98 (90.7 %, 95 % CI 85.3 to 96.2), 114 (92.7 %, 88.1 to 97.3), and 126 (92.6 %, 88.3 to 97.0) positives were detected. Subsequent test rounds yielded 10 (9.3 %, 3.8 to 14.7), 9 (7.3 %, 2.7 to 11.9), and 10 (7.4 %, 3.0 to 11.7) extra positives. In the non-epidemic setting EIA, toxigenic culture and PCR detected 33, 66, and 83 positives. The three tests combined 93 detected positives. In the first test round 30 (90.9 %, 81.1 to 100.7), 63 (95.5 %, 90.4 to 110.5), 76 (91.6 %, 85.6 to 97.5), and 87 (93.5 %, 88.6 to 98.5) positives were detected. Subsequent test rounds yielded 3 (9.1 %, −0.7 to 18.9), 3 (4.5 %, −0.5 to 9.6), 7 (8.4 %, 2.5 to 14.4), and 6 (6.5 %, 1.5 to 11.4) extra positives. In conclusion, repeat testing resulted in 4.5 % to 9.3 % extra positives. No significant difference between the settings studied could be demonstrated. Repeat sampling and multimodality testing may be chosen in an outbreak situation to detect all cases, effectively controlling nosocomial spread.

Steingrimsson, S.; Thimour-Bergström, L.; Roman-Emanuel, C.; Scherstén, H.; Friberg, Ö.; Gudbjartsson, T.; Jeppsson, A.

doi: 10.1007/s10096-015-2485-8pmid: 26432552

Surgical site infection is a common complication following cardiac surgery. Triclosan-coated sutures have been shown to reduce the rate of infections in various surgical wounds, including wounds after vein harvesting in coronary artery bypass grafting patients. Our purpose was to compare the rate of infections in sternotomy wounds closed with triclosan-coated or conventional sutures. A total of 357 patients that underwent coronary artery bypass grafting were included in a prospective randomized double-blind single-center study. The patients were randomized to closure of the sternal wound with either triclosan-coated sutures (Vicryl Plus and Monocryl Plus, Ethicon, Inc., Somerville, NJ, USA) (n = 179) or identical sutures without triclosan (n = 178). Patients were followed up after 30 days (clinical visit) and 60 days (telephone interview). The primary endpoint was the prevalence of sternal wound infection according to the Centers for Disease Control and Prevention (CDC) criteria. The demographics in both groups were comparable, including age, gender, body mass index, and rate of diabetes and smoking. Sternal wound infection was diagnosed in 43 patients; 23 (12.8 %) sutured with triclosan-coated sutures compared to 20 (11.2 %) sutured without triclosan (p = 0.640). Most infections were superficial (n = 36, 10.1 %), while 7 (2.0 %) were deep sternal wound infections. There were 16 positive cultures in the triclosan group and 17 in the non-coated suture group (p = 0.842). The most commonly identified main pathogens were Staphylococcus aureus (45.4 %) and coagulase-negative staphylococci (36.4 %). Skin closure with triclosan-coated sutures did not reduce the rate of sternal wound infection after coronary artery bypass grafting. (clinicaltrials.gov: NCT01212315)

Bergal, A.; Loucif, L.; Benouareth, D. E.; Bentorki, A. A.; Abat, C.; Rolain, J.-M.

doi: 10.1007/s10096-015-2487-6pmid: 26415872

This study describes, for the first time, the genetic and phenotypic diversity among 93 Streptococcus agalactiae (group B Streptococcus, GBS) isolates collected from Guelma, Algeria and Marseille, France. All strains were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The molecular support of antibiotic resistance and serotyping were investigated by polymerase chain reaction (PCR). The phylogenetic lineage of each GBS isolate was determined by multilocus sequence typing (MLST) and grouped into clonal complexes (CCs) using eBURST. The isolates represented 37 sequence types (STs), 16 of which were novel, grouped into five CCs, and belonging to seven serotypes. Serotype V was the most prevalent serotype in our collection (44.1 %). GBS isolates of each serotype were distributed among multiple CCs, including cps III/CC19, cps V/CC1, cps Ia/CC23, cps II/CC10, and cps III/CC17. All isolates presented susceptibility to penicillin, whereas resistance to erythromycin was detected in 40 % and tetracycline in 82.2 % of isolates. Of the 37 erythromycin-resistant isolates, 75.7 % showed the macrolide–lincosamide–streptogramin B (MLSB)-resistant phenotype and 24.3 % exhibited the macrolide (M)-resistant phenotype. Constitutive MLSB resistance (46 %) mediated by the ermB gene was significantly associated with the Guelma isolates, whereas the M resistance phenotype (24.3 %) mediated by the mefA/E gene dominated among the Marseille isolates and belonged to ST-23. Tetracycline resistance was predominantly due to tetM, which was detected alone (95.1 %) or associated with tetO (3.7 %). These results provide epidemiological data in these regions that establish a basis for monitoring increased resistance to erythromycin and also provide insight into correlations among clones, serotypes, and resistance genes.

Lerche, C.; Christophersen, L.; Trøstrup, H.; Thomsen, K.; Jensen, P.; Hougen, H.; Bundgaard, H.; Høiby, N.; Moser, C.

doi: 10.1007/s10096-015-2488-5pmid: 26440039

The empiric treatment of infective endocarditis (IE) varies widely and, in some places, a regimen of penicillin in combination with an aminoglycoside is administered. The increasing incidence of Staphylococcus aureus IE, poor tissue penetration by aminoglycosides and low frequency of penicillin-susceptible S. aureus may potentially lead to functional tobramycin monotherapy. Therefore, this study aimed to evaluate tobramycin monotherapy in an experimental S. aureus IE rat model. Catheter-induced IE at the aortic valves were established with S. aureus (NCTC 8325-4) and rats were randomised into untreated (n = 22) or tobramycin-treated (n = 13) groups. The treatment group received tobramycin once-daily. Animals were evaluated at 1 day post infection (DPI), 2 DPI or 3 DPI. Quantitative bacteriology and cytokine expression were measured for valves, myocardium and serum. A decrease of bacterial load was observed in valves and the spleens of the treated (n = 6) compared to the untreated group at 2 DPI (n = 8) (p ≤ 0.02 and p ≤ 0.01, respectively), but not at 3 DPI (n = 7). Quantitative bacteriology in the myocardium was not different between the groups. Keratinocyte-derived chemokine (KC) in the aortic valves was significantly reduced at 2 DPI in the tobramycin-treated group (p ≤ 0.03). However, the expression of interleukin (IL)-1b, IL-6 and granulocyte-colony stimulating factor (G-CSF) in the valves was not different between the two groups. In the myocardium, a significant reduction in IL-1b was observed at 2 DPI (p ≤ 0.001) but not at 3 DPI. Tobramycin as functional monotherapy only reduced bacterial load and inflammation transiently, and was insufficient in most cases of S. aureus IE.

Cheng, V.; Chen, J.; So, S.; Wong, S.; Yan, M.; Chau, P.; Lee, W.; To, K.; Chan, J.; Hung, I.; Ho, P.; Yuen, K.

doi: 10.1007/s10096-015-2489-4

Vitali, B.; Cruciani, F.; Picone, G.; Parolin, C.; Donders, G.; Laghi, L.

doi: 10.1007/s10096-015-2490-ypmid: 26385347

In this study, we sought to find novel bacterial and metabolic hallmarks for bacterial vaginosis (BV). We studied the vaginal microbiome and metabolome of vaginal fluids from BV-affected patients (n = 43) and healthy controls (n = 37) by means of an integrated approach based on quantitative polymerase chain reaction (qPCR) and proton nuclear magnetic resonance (1H-NMR). The correlations between the clinical condition and vaginal bacterial communities were investigated by principal component analysis (PCA). To define the metabolomics signatures of BV, 100 discriminant analysis by projection on latent structure (PLS-DA) models were calculated. Bacterial signatures distinguishing the health condition and BV were identified by qPCR. Lactobacillus crispatus strongly featured the healthy vagina, while increased concentrations of Prevotella, Atopobium and Mycoplasma hominis specifically marked the infection. 1H-NMR analysis has led to the identification and quantification of 17 previously unreported molecules. BV was associated with changes in the concentration of metabolites belonging to the families of amines, organic acids, short chain fatty acids, amino acids, nitrogenous bases and monosaccharides. In particular, maltose, kynurenine and NAD+ primarily characterised the healthy status, while nicotinate, malonate and acetate were the best metabolic hallmarks of BV. This study helps to better understand the role of the vaginal microbiota and metabolome in the development of BV infection. We propose a molecular approach for the diagnosis of BV based on quantitative detection in the vaginal fluids of Atopobium, Prevotella and M. hominis, and nicotinate, malonate and acetate by combining qPCR and 1H-NMR.

Marchisio, P.; Santagati, M.; Scillato, M.; Baggi, E.; Fattizzo, M.; Rosazza, C.; Stefani, S.; Esposito, S.; Principi, N.

doi: 10.1007/s10096-015-2491-xpmid: 26385346

This paper reports the results of the first study in which Streptococcus salivarius 24SMB, a safe α-haemolytic strain capable of producing bacteriocin-like substances with significant activity against acute otitis media (AOM) pathogens, was intranasally administered in an attempt to reduce the risk of new episodes of AOM in otitis-prone children. In this prospective, randomized, double-blind, placebo-controlled study, 100 children aged 1–5 years with histories of recurrent AOM were randomized 1:1 to receive an intranasal S. salivarius 24SMB or placebo twice daily for 5 days each month for 3 consecutive months. Fifty treated children and 47 who received placebo who were compliant with study protocol were followed monthly for 6 months. The number of children who did not experience any AOM was higher among the children treated with the S. salivarius 24SMB preparation than among those in the placebo group (30.0 vs 14.9 %; p = 0.076). Moreover, the number of children who received antibiotics during the study period was lower among the children treated with S. salivarius 24 SMB than among those who received placebo (70 vs 83.0 %; p = 0.13). Compared with the children who were not colonized by S. salivarius 24SMB after treatment, the number of colonized children who experienced any AOM was significantly lower (42.8 vs 13.6 %; p = 0.03). Similar results were observed when the children treated with antibiotics for AOM were analysed (67.8 vs 95.5 %; p = 0.029). This study revealed the ability of intranasally administered S. salivarius 24SMB to reduce the risk of AOM in otitis-prone children.

Fredborg, M.; Rosenvinge, F.; Spillum, E.; Kroghsbo, S.; Wang, M.; Sondergaard, T.

doi: 10.1007/s10096-015-2492-9pmid: 26407621

Rapid antimicrobial susceptibility testing (AST) is essential for early and appropriate therapy. Methods with short detection time enabling same-day treatment optimisation are highly favourable. In this study, we evaluated the potential of a digital time-lapse microscope system, the oCelloScope system, to perform rapid AST. The oCelloScope system demonstrated a very high accuracy (96 % overall agreement) when determining the resistance profiles of four reference strains, nine clinical isolates, including multi-drug-resistant isolates, and three positive blood cultures. AST of clinical isolates (168 antimicrobial agent–organism combinations) demonstrated 3.6 % minor, no major and 1.2 % very major errors of the oCelloScope system compared to conventional susceptibility testing, as well as a rapid and correct phenotypic detection of strains with methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum β-lactamase (ESBL) profiles. The net average time-to-result was 108 min, with 95 % of the results being available within 180 min. In conclusion, this study strongly indicates that the oCelloScope system holds considerable potential as an accurate and sensitive AST method with short time-to-result, enabling same-day targeted antimicrobial therapy, facilitating antibiotic stewardship and better patient management. A full-scale validation of the oCelloScope system including more isolates is necessary to assess the impact of using it for AST.