**6. Mechanisms of resistance**

is usually tailored with a disinfectant and strength of choice for that particular pathogen. This process usually includes initial removal of all detachable objects from the room, such as bedding and curtains. The terminal clean also includes wiping down any ventilation components on the ceiling or lighting. Finally, all other surfaces and sites are cleaned downward toward the floor level, and all equipment and items that were removed from the room are wiped over with disinfectant before returning to the room. Automated technologies have been recently introduced and may offer enhanced decontamination. Although these

In the following study, terminal cleaning, combined with standard infection control polices resulted in 70–40% reduction in patients colonized with MDR *Enterobacteriaceae*. These results were attributed to the overall combined intervention. Universal decolonization has been conducted in many ICUs; particularly, after the results of a landmark trial called REDUCE MRSA [33]. Huang et al. concluded that routine ICU practice and universal decolonization was more effective than targeted decolonization or screening [40]. The universal decolonization was effective at reducing rates of MRSA and bloodstream infection from any pathogen. In the treatment group, the number needed to treat (to prevent one) bloodstream infection was per 99 patients. Other technologies have been explored such automated decontamination devices which include peroxide and UV light. As mentioned earlier, these automated technologies could possibly offer some improvement, but they should not replace routine daily cleaning. Common pitfalls for these techniques include additional training of staff, management and personnel oversight, logistical complexities, and costs of equipment. Future studies are war-

The Affordable Care Act in 2015 mandated that the hospital-acquired condition (HAC) reduction program reduce hospital payments by 1% for hospitals performing at the lowest ranked 25% with regard to hospital-acquired conditions. These conditions include Catheter Associated Urinary Tract Infections (CAUTI) and Central Line Associated Bloodstream Infections (CLABSI). As of 2017, CMS has also added both CDI and MRSA to the program. Given that hospitals are now accountable for these conditions, it is imperative that they have robust infection control policies and procedures and have also successfully implemented antimicrobial stewardship programs as defined by the Joint Commission Medication Management

Surveillance systems allow the evaluation of the local and regional healthcare associated infections (HAI) and antimicrobial resistance (AMR) patters. Surveillance systems contribute to the early detection of HAI and new patterns of AMR, including identifying new clusters or outbreaks. Surveillance is a key component on a local, regional, national, and even on a global scale (WHO) for determining these patterns [44]. Knowing and identifying resistance patterns can help provide guidance to practitioners by means of antibiograms. Antibiograms give the clinician the most appropriate empiric antibiotic information choice while awaiting further confirmation by either phenotypic or genotypic means. The CDC will soon require hospitals

technologies are automated they do not replace routine daily cleaning [39].

ranted to evaluate overall costs versus benefits [39].

(MM) Standard MM.09.01.01 [41–43].

**5. Surveillance**

84 Contemporary Topics of Pneumonia

Microorganisms are tenacious at survival, they have been on the Earth for billions of years, and their sole existence is based on their ability to adapt to the environment. This ability for survival despite the introduction of antibiotics is best described antimicrobial resistance. The mechanisms of antimicrobial resistance are as follows: (a) enzymatic degradation of antibiotics via hydrolytic enzymes, (b) alteration of bacterial proteins or target sites, and (c) changes in membrane permeability to antibiotics either by penetration or by expulsion of the actual antibiotic from within the bacteria. Antibiotic resistance can be either plasmid or chromosomal mediated. One of the most important mechanisms of resistance to beta-lactams is enzymatic hydrolysis of the ring structure resulting in inactivity [45]. The chromosomal β-lactamases expression can either be depressed or induced or by the exposure to β-lactam antibiotics. Overcoming resistance to β-lactam antibiotics includes the coadministration of inhibitors to protect the ring structure, and the development of new antibiotics that are stable against enzymatic degradation. By adding a β-lactamase inhibitor to a β-lactam antibiotic, this allows the β-lactam to avoid enzymatic hydrolysis and perform its bactericidal effects. The following are examples of resistance [45]:


Bacterial resistance to β-lactam antibiotics as mentioned earlier is mediated via β-lactamases; this mode is the primary mechanism of resistance. Ambler molecular classification is used to classify β-lactamases and is based on the amino acid sequence and divides the class into four (A, B, C, and D). A, C, and D enzymes utilize serine for β-lactam hydrolysis and class B metalloenzymes require zinc bivalent metal ion, usually Zn2+ ions for substrate hydrolysis [46–48].

selection of the most appropriate empiric antimicrobial regimen may be difficult for the clinician based, appropriate history, comorbidities, risk factors for resistant pathogens, and the complexity of patient transitions of care. Clinicians for decades have depended on phenotypic testing that detects the activity of enzymes (i.e., hydrolysis of antibiotics such as beta-lactams *in vitro*) to provide definitive guidance on antimicrobial therapy. These tests provide the clinician pathogen identity with sensitivity, which may have a turn-around time of up to 72 h. As mentioned above, timing of appropriate antimicrobial therapy is key for patient survival in the critically ill, especially with septic shock. New technological advancements in both phenotypic and genotypic testing (molecular tests that detect the resistance mechanisms of a specific gene) commonly known as "rapid diagnostics" will be able to provide detailed information within several hours versus current standards (48–72 h) [53–56].

Multidrug-Resistant Gram-Negative Pneumonia and Infection in Intensive Care Unit

http://dx.doi.org/10.5772/intechopen.69377

87

Procalcitonin (PCT) is an inflammatory biomarker that is an acute phase reactant that reflects host response to bacterial infections. PCT synthesis is up regulated in the presence of bacterial toxins and certain bacterial pro-inflammatory mediators such as TNFα (tumor necrosis factor alpha), interleukin (IL)-1b, IL-6. PCT is neutral to cytokines that are normally released for viral

> Detects (w/o distinction) all three types of carbapenemases: Class A: KPC

<2 h (after positive culture growth, ~24–48 h)

18–24 h (after positive culture growth, ~24–48 h)

If results required within same day can be read after 6 h, but prefer reading results after 12–24 h (after positive culture growth, ~24–48 h)

2–4 h

Class B: NDM/VIM/IMP Class D: OXA

Provides bacterial (or fungal) identification at the species, genus, or group level (detects carbapenemase activity)

Only confirms the presence of carbapenemases (does not identify specific carbapenemase (i.e., KPC

Only confirms the presence of carbapenemases (does not identify specific carbapenemase (i.e., KPC

vs. NDM)

vs. NDM)

**Manufacturer/product name Methodology Detection results Turnaround time**

**Rapid nonnucleic acid–based tests and other phenotypic tests (MHT/CIM)**

hydrolyzed

Modified Hodge test (MHT) CLSI suggested phenotypic

Detects pH shifts by phenol red indicator that occurs when imipenem is

Detects change in native carbapenem mass

confirmatory test. Enhanced growth = (+) for carbapenemase production No enhanced growth = (-) for carbapenemase

Phenotypic confirmatory

production

test

**Table 2.** Rapid diagnostic testing methodologies.

See **Tables 2** and **3**.

BioMérieux Rapidec Carba -NP

BioMerieux MALDI-TOF MS VItek—MS

(matrix-assisted laser desorption ionization time of flight mass spectrometry)

Carbapenemase Inactivation

method (CIM)

Example enzymes are as follows:


Multidrug efflux mechanisms in bacteria contribute significantly to intrinsic and acquired resistance to many antibiotics. Whole genome sequencing has confirmed the broad distribution of these systems in Gram-negative as well as in Gram-positive bacteria. Multidrug efflux systems have given rise to high-level resistance to Gram-negatives, particularly when multiple mechanisms or resistances are simultaneously produced by a single isolate. The efflux system is mediated by transport proteins, which confer resistance antimicrobial agents. The tripartite efflux system in Gram-negative bacteria is necessary to expel the antibiotic to the outer medium. The system consists of (a) protein localized in the cytoplasmic membrane, (b) protein located in the periplasmatic space, and (c) a third protein located in the outer membrane. These active transport proteins are grouped in families, which are based on their amino acid sequences and mechanisms. The most identified and studied multidrug efflux systems among Gram-negative bacteria are *P. aeruginosa* and *E. coli* [49].
