Searching the next remedies within the bacterial arsenal

Charalampia Korea

Pharmassist Ltd, Contract Research Organisation, Holargos, Athens, Greece

Biofilms are bacterial communities, often multi-species, attached on abiotic or biotic surfaces and enclosed in an extracellular matrix. The matrix is composed of extracellular polymeric substances (EPS) such as proteins, polysaccharides and bacterial DNA. Biofilm formation occurs in four steps: first contact, attachment, maturation, and dispersion. After initial adhesion, if the environmental conditions are favorable, this reversible adhesion can lead to irreversible attachment and extracellular matrix production, thus to micro-colony formation and biofilm maturation. Several bacterial adhesins (Type 1 pili, P pili, curli) and biofilm-related molecules, eg. EPS or Quorum sensing molecules are closely involved in all steps of biofilm formation and can be responsible for biofilm persistence.

In the medical sector the particularly resistant profile of biofilms poses serious problems both in the diagnosis of the biofilm-associated infections (BAI) as well as in their eradication. Indeed, biofilm infections exhibit 10 to 1000 times higher resistance to the antibiotic therapies used in clinical practice.

This recalcitrance seems to be due to the i) reduced penetration of antibiotics into the EPS, ii) the arise of persisters, ie of cells with a particularly resistant phenotype and iii) the presence of bacteria that have activated stress responses after sensing the induced chemical stress provoked by antibiotics within the matrix.

Up to date it is known that biofilms of medical relevance can be responsible for a series of chronic infections, such as endocarditis, cystic fibrosis, chronic bronchopneumonia, persistent otitis media, chronic rhinosinusitis, chronic osteomyelitis. Further to this biofilms can be also responsible for nosocomial infections related to foreign body medical devices e.g., catheters, prosthetic heart valves, pacemakers and stents.

The present review presents the current experimental and clinical approaches related to the development of prevention strategies and therapies against biofilm-associated infections. The most recent advances include compounds that can either prevent the bacterial adhesion itself or inhibit a series of biofilm-related structures and proteins. Moreover the progress on the development of vaccines using biofilm-related virulence factors is briefly presented.

Their understanding can pave the way for the discovery and development of diagnostic tools and targeted therapies for an efficient clinical management of the biofilm associated infections.

Key words

biofilms, therapies, anti-adhesive compounds,quorum sensing inhibitors (QSI)

Hand Hygiene – Focus on surgical patient care

Elisavet Kousouli1, Kostantina Polymeri1, Olympia Zarkotou1,2, Katina Themeli-Digalaki1,2

1.Infection Control Committee

2.Department of Microbiology, Tzaneio General Hospital of Piraeus

Hospital acquired infections (HAI) and antimicrobial resistance represent a serious threat to patient safety and healthcare systems globally and especially in our country. Hand hygiene (HH) promotion seems to be the cornerstone of infection control interventions as it is the most important measure to prevent transmission of pathogens by healthcare workers (HCWs). There is clear evidence that strict adherence to HH reduces the risk of cross-transmission. HH practices are well known, however, compliance is low and many factors (cultural and behavioral issues among them) have been implicated. Behavioral change seems to be crucial for improving HH compliance, though is quite difficult to be achieved and requires multifaceted techniques. World Health Organization (WHO) proposes a layered strategy to improve compliance. In 2005, WHO launched the first global HH campaign. The primary focus of 2016 WHO’s campaign is the surgical patient’s care, as proper implementation of HH significantly contributes to the reduction of surgical site infections (SSIs). SSIs are quite prevalent, especially in middle and low-income countries and they have important impact on patients’ outcomes. Their prevention is complex, multimodal, multi-disciplinary and rather challenging. The key risk factor for SSIs is the poor adherence and incorrect HH procedures during perioperative and postoperative care. Surgical hand disinfection procedures include surgical scrub and surgical rub. According to current guidelines, both methods are considered suitable, though several factors favor the use of hand rub, including rapidity of action and thus time savings and fewer side-effects. Improving hand hygiene practices in all surgical services is the leading prevention measure to make surgery safer worldwide.

Key words

hand hygiene, hospital acquired infections, surgical patient care, compliance

Five-year trends of antimicrobial drugs consumption and incidence of bloodstream infections caused by multidrug-resistant pathogens in a Greek ICU

Olympia Zarkotou1,2, Kalliopi Avgoulea1, Panagiota Papagiannakopoulou3, Christina Louka1,

David Symeonidis4, Konstantina Chrysou4, Elisavet Kousouli2, Georgios Chrysos2,4,

Katina Themeli-Digalaki1,2, Athanassios Tsakris5, Spyros Pournaras5

1Department of Microbiology, 2Infection Control Committee, 3Pharmacy and 4Infectious Diseases Unit,

Tzaneio General Hospital of Piraeus, Athens, Greece

5Department of Microbiology, Medical School, National & Kapodistrian University of Athens, Athens, Greece

Excessive and inappropriate use of antibiotics enhances the emergence of antimicrobial resistance, resulting into a vicious cycle. Continuous surveillance of antibiotic consumption and implementation of antibiotic stewardship programs (ASP) is an important component of infection control interventions. Greece is a high endemicity area for multidrug resistant pathogens (MDR), especially carbapenem-resistant (CR) Gram-negatives (GN), and moreover antibiotic consumption is among the highest in Europe. Aim of this study was to record antibiotic consumption and the incidence of bloodstream infections (BSI) caused by MDR pathogens in our 12-bed general ICU, before initiating an ASP in the hospital. Trends over time were also evaluated.

An observational study was performed from January 2010 to December 2014. Consumption data were retrospectively collected from the hospital pharmacy records and expressed as daily defined doses (DDD) per 1000 patient-days (PD). All BSI episodes caused by CR Klebsiella pneumonia (CRKP), CR Acinetobacter baumannii (CRAB), CR Pseudomonas aeruginosa (CRPA), vancomycin-resistant Enterococcus spp (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) were prospectively recorded. Identification was performed by conventional or automated methods (Vitek 2 Compact, bioMerieux). Antimicrobial susceptibility testing and MIC values determination was performed by Vitek 2 and Etest (bioMerieux). We recorded 395 BSI episodes caused by the study pathogens, with a mean annual incidence of 21.21/1000 PD. The incidence declined from 22.95 in 2011 to 17.90/1000 PD in 2013, however, a significant increase was observed in 2014 (25.21/1000 PD, p= 0.03). No correlations between the consumption of antimicrobial agents (AMA) and incidence data were found. The predominant pathogens were CRAB and CRKP. Antibiotic use was high in all 5 years of the study with a mean annual consumption of 3077 DDD/1000 PD. The most common AMA prescribed was ampicillin/sulbactam (17.7%), followed by meropenem (16.8%) and colistin (11.8%). Τhe total AMA consumption rose by 20.3% from 2010 to 2014 (p= 0.18). The rate of change in AMA use was more remarkable for quinolones (128.4%, p= 0.004) and colistin (66.1%, p= 0.02). A decreasing trend was observed for only few antimicrobials, such as tigecycline (-48.5 %, p= 0.12) and daptomycin (-93%, p= 0.012). Total AMA use temporary decreased in 2011 (-21.3%, p= 0.33) and a continuous and significant increasing trend was observed thereafter (p= 0.022).

In conclusion, the local epidemiology of resistance defines the antimicrobial decision-making. In our setting, the high incidence of CRGN imposes the use of broad-spectrum and last resort AMA. In the era of growing resistance and limited treatment options, judicious antibiotic use is crucial. Our surveillance data increase our awareness and necessitate the ASP launching, so as to optimize antibiotic prescribing and preserve the effectiveness of last resort antimicrobials.

Key words

antibiotic surveillance, antimicrobial use, consumption of antimicrobials, antibiotic stewardship, intensive care unit, carbapenem resistance, multidrug-resistant pathogens

Infectious diseases in Athens during the German Occupation (1941-1944)

Constantinos Tsiamis1, Georgia Vrioni1, Evangelos Vogiatzakis2, Effie Poulakou-Rebelakou3,

Kalliopi Theodoridou1, Dimitrios Anoyatis-Pele4, Athanassios Tsakris1

1.Department of Microbiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece

2.Department of Microbiology, General Chest Hospital “Sotiria”, Athens, Greece

3.Department of History of Medicine, Medical School, National and Kapodistrian University of Athens,

Athens, Greece

4.Faculty of History, Ionian University, Corfu, Greece

The aim of the study is to present the second most frequent cause of death in Athens, during the German Occupation (1941-1944), which was the infectious diseases. Until now the majority of studies have focused to the great famine of 1941-42 with thousands of victims. Although the famine was the main cause of death, a significant number of cases were due to infection diseases or non-communicable diseases. The study was based on the archives, such as the books of admissions of the hospitals located in Athens, but also to the official public records of the Prefecture of Athens. From the study of the archival material it is evident that tuberculosis, malaria, epidemic typhus, typhoid fever and meningitis, were the most important causes of morbidity and mortality. During the German Occupation, tuberculosis and malaria significantly increased. While epidemic outbreaks reported of epidemic typhus (1941), malaria (1942) and food-born poisoning of bacterial etiology (1941, 1942 and 1943). It is worth mentioning that there was an increase of syphilis, genital warts, pediculosis and scabies.

The topographic study indicated that the southwest and southeast areas of the Municipality of Athens, and the bordering Municipalities, were areas with higher morbidity and mortality. These areas were the residence of the working social class and the refugees from the Asia Minor (1922).

The increase of morbidity and mortality in these areas can be explained by the low social-economic living conditions, since the Interwar period, the deterioration due to the Occupation, and the population density. The spectrum of the infectious diseases in Athens was not significantly different from that of Interwar. The difference was the increase of the cases due to the miserable living conditions and the collapse of the public services for the surveillance and control of the infectious diseases.

Key words

Athens, German Occupation, History of Microbiology, Infectious diseases, Public Health