**2. Carbapenem resistance**

Nosocomial infections caused by Gram-negative bacteria resistant to carbapenems, mostly multiple-resistant, represent a challenge due to limited treatment options [2, 3]. Like other beta-lactamines, the carbapenems are included in preferred treatment regimens for various infectious diseases [4]. Antibiotic-resistant patterns of bacterial isolates from nosocomial infections are continuously changed. Therefore, it is of highest interest in finding alternative methods for preventing contamination with multidrug-resistant strains. Since ancient times, people have had an intuitive feeling that some spices have real benefits not only as air fresheners but also in that era they were the only therapeutic option for many diseases. Thus, they correctly guessed that concentrated lotions/oils are not only more efficient but easy to use and to store. Essential oils (EOs) from natural products proved their positive effects in various clinical conditions. Although the specific mechanisms of their components are not deciphered, many studies demonstrated certain biological activity of some phytochemicals. Terpinen-4-ol found in many EOs are demonstrated to act synergistically with chemotherapeutic agents in digestive malignancies [5]. There are many studies about antibacterial effects of EOs, mainly on supragingival plaque. The results are not constant, for example, some authors do not find

Antibiotic-resistance genes are nowadays a constant presence not only in the hospital environment but are also more and more demonstrated in various ecosystems [7–9]. Antibioticresistance genes naturally already exist in organisms living in most diverse environments. Surely, antibiotic-resistance genes have an essential role in maintaining of inter-species equilibrium on specific ecosystems [10]. All living things from prokaryotes to eukaryotes are constantly exposed to a huge mixture of organic and inorganic compounds. Even if, nowadays, accurate methods exist to isolate and to characterize antibiotic-resistant microorganisms, it is not possible to calculate the influence of a myriad factors that interfere in every environment. An interesting study demonstrated the utility of transmission electron microscopy for observing of aquatic microorganism structural abnormalities in different environmental conditions [11]. The terrestrial ecosystem is also prone to be reshaped by human activities [12]. Intensive farming implies antibiotics, so the spread of intestinal bacteria which harbor antibiotic-resistance genes is an immediate consequence. This does not imply that once a certain bacteria species is present in a certain geographic area its antibiotic-resistance pattern remains unchanged. Atmospheric conditions, notably rainfalls, could contribute to spreading of contaminants from the soil to groundwater and greatly alter the count of microorganisms. Different bacterial species do not behave the same, antibiotic-resistance patterns differently changed, but certain beta-lactamines could be used as indicators of antibiotic resistance at least for *Escherichia coli* [13]. Consequently, it is not wrong to include antibiotic-resistance genes into the long list of environmental pollutants [14]. The physicians require bacteriological diagnosis on admission of the patients in ICUs and for surveillance of any nosocomial infection. For respiratory infections, Gram smears from sputum, endotracheal aspirate, or bronchoalveolar lavage are mandatory. Very often in ICUs, respiratory infections are due to carbapenem-resistant Gram-negative bacilli. In our opinion, testing volatile EOs, as complementary substances, for prevention of respiratory infections is not a futile idea. Finally, last but not least, wide use of antibiotics alters not only the hospital environment but also disturbs other ecological niches (water and soil). These topics will be

a positive effect of tea tree oil on supragingival plaque [6].

54 Contemporary Topics of Pneumonia

our concern in the next sections.

The carbapenems are sometimes the last-resort antibiotics for treating of extended spectrum beta-lactamase (ESBL) producing Gram-negative bacteria. But carbapenem resistance is increasingly reported in *Enterobacteriaceae* and nonfermenters like *Acinetobacter* spp. or *Pseudomonadaceae*. Carbapenem resistance is mainly due to carbapenemase (E.C. 3.5.2.6) production. Structural classification of beta-lactamases implies the primary structure (sequence homology) and distinguishes four molecular classes of beta-lactamases— A, C, D (serine beta-lactamases), and B (MBL-metallo beta-lactamase) [15–17]. Functional classifications of beta-lactamases are more closer to clinical issues [18, 19] and recognize three groups of beta-lactamases: Group 1 (Class C) cephalosporinases; Group 2 (Classes A and D) broad-spectrum beta-lactamases, inhibitor-resistant beta-lactamases, extendedspectrum beta-lactamases, serine carbapenemases, and Group 3 metallo-beta-lactamases. So far in this section, we have taken in consideration only different types of beta-lactamases as a resistance mechanism. Besides producing carbapenemases, the reduction of carbapenem influx into the periplasma is commonly observed in clinical isolates. Different mutations in porins significantly contribute to the failing of drug accumulation at appropriate concentration in periplasmic space; therefore, carbapenem resistance is often more complex than one thought at the first sight [20]. Readers, who wish to know further details regarding carbapenem resistance, should consult excellent papers devoted to this particular topic [21–24].
