**11. Conclusion**

Antimicrobial resistance has risen at threating levels within the past few decades and has contributed to an economic burden on healthcare expenditures. Several governmental agencies including the WHO, CDC, and the White House are focused on combating antimicrobial resistance at various steps. Acquisition of multidrug-resistant organisms in patients has established an

**Drug name** Zabofloxacin

S-649266 Omadacycline

Lefamulin (BC-3781)

Imipenem/

Phase 3

cilastatin+relebactam

(MK-7655)

Iclaprim Cadazolid Taksta (fusidic acid)

Carbavance (vaborbactam+

Phase 3

meropenem)

Baxdela (delafloxacin)

Eravacycline

Plazomicin Solithromycin 1 and phase 2 is available from this site.

**Table 7.**

New antibiotics currently in clinical development.

Phase 3 Phase 3

Phase 3

Phase 3

Phase 3

Phase 3

Actelion Pharmaceuticals

Ltd.

Cempra Inc. Rempex Pharmaceuticals

Meropenem+novel boronic

Yes

beta-lactamase inhibitor

Inc. (wholly owned

subsidiary of the

Medicines Co.)

Melinta Therapeutics

Fluoroquinolone

Possible

Possible

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

Inc.

Tetraphase

Tetracycline

Yes

Yes

Pharmaceuticals Inc.

Achaogen Inc.

Cempra Inc.

Aminoglycoside

Macrolide (fluoroketolide)

*Source*: Adopted with permission from: http://www.pewtrusts.org/~/media/assets/2016/05/antibiotics-currently-in-clinical-development.pdf. Full table for drugs in phase

 No

Yes

Yes

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

95

Yes

Fusidane

No

No

Yes

Phase 3

Motif Bio PLC

Dihydrofolate reductase

No

No

Yes

(DHFR) inhibitor

Quinolonyl- oxazolidinone

 No

Phase 3

Phase 3 Phase 3

Phase 3

Dong Wha

Fluoroquinolone

No

Pharmaceutical Co. Ltd

Shionogi Inc. Paratek Pharmaceuticals

Tetracycline

Inc.

Nabriva Therapeutics

Pleuromutilin

No

No

No

Yes

AG

Merck & Co. Inc.

Carbapenem+novel betalactamase inhibitor

Yes

Cephalosporin

Yes Yes

Yes

Possible

**Development phase**

**Company**

**Drug class**

**Expected activity against** 

**Expected activity against** 

**a CDC urgent threat** 

**pathogen?4**

No

**resistant Gram-negative** 

**ESKAPE pathogens?**

**7**. The critical access hospital collects, analyzes, and reports data on its antimicrobial stewardship program **Note:** *Examples of topics to collect and analyze data on may include evaluation of the antimicrobial stewardship program, antimicrobial prescribing patterns, and antimicrobial resistance patterns*


office-based surgery practices in standard with the following governmental and professional organizations: Centers for Medicare & Medicaid Services (CMS), the CDC, and the Society for

**8**. The critical access hospital takes action on improvement opportunities identified in its antimicrobial stewardship

Adopted from https://www.jointcommission.org/assets/1/6/New\_Antimicrobial\_Stewardship\_Standard.pdf.

**7**. The critical access hospital collects, analyzes, and reports data on its antimicrobial stewardship program **Note:** *Examples of topics to collect and analyze data on may include evaluation of the antimicrobial stewardship program, antimicrobial prescribing patterns, and antimicrobial* 

*resistance patterns*

There has been emergence and increase of MDR pathogens. Efforts have been made toward adequate treatment, daily de-escalation regimen as well as antibiotic stewardship programs. The pipeline for the new drugs is still sparse. **Table 7** illustrates the antibiotics that are in the phase 3 trials. Only very few have an expected activity against the CDC urgent threat potential (**Table 7**).

Antimicrobial resistance has risen at threating levels within the past few decades and has contributed to an economic burden on healthcare expenditures. Several governmental agencies including the WHO, CDC, and the White House are focused on combating antimicrobial resistance at various steps. Acquisition of multidrug-resistant organisms in patients has established an

Healthcare Epidemiology of America (SHEA) (**Table 6**).

**Table 6.** The New Joint Commission antimicrobial stewardship standard: MM.09.01.01.

**6**. The critical access hospital's antimicrobial stewardship program uses organization-approved multidisciplinary protocols (for example, policies and procedures). **Note:** *Examples of protocols are as follows:* • *Antibiotic Formulary Restrictions*

• *Assessment of Appropriateness of Antibiotics for Skin and* 

• *Assessment of Appropriateness of Antibiotics for Urinary* 

• *Preauthorization Requirements for Specific Antimicrobials*

• *Care of the Patient with Clostridium difficile (c. -diff)*

• *Guidelines for Antimicrobial Use in Adults* • *Guidelines for Antimicrobial Use in Pediatrics* • *Plan for Parenteral to Oral Antibiotic Conversion*

• *Use of Prophylactic Antibiotics*

program. (*See also* MM.08.01.01, EP 6)

• *Assessment of Appropriateness of Antibiotics for Community-Acquired Pneumonia*

*Soft Tissue Infections*

94 Contemporary Topics of Pneumonia

*Tract Infections*

**10. Future pipeline in phase III development**

**11. Conclusion**

**Table 7.** New antibiotics currently in clinical development. 95

independent risk factor for mortality. Clinical expertise, risk stratification, surveillance, infection control, and the use of rapid diagnostics may be key to early identification of resistant pathogens; furthermore, appropriate antimicrobial selection and dose optimization via PK/PD are critical in improving outcomes and survival. Various studies have demonstrated the correlation between survival and appropriate early initial antibiotics. Antimicrobial stewardship programs have been shown to reduce antimicrobial resistance and are now considered a regulatory mandate. CMS and TJC have developed guidance for accreditation as it relates to demonstrating an effective antimicrobial stewardship program, including developing publicly reportable measures.

[3] Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, Scheld M, Spellberg B, Bartlett J. Bad bugs, no drugs: No ESKAPE! An update from the Infectious Diseases Society of America. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 2009;**48**(1):1-12 [PMID: 19035777 DOI: 10.1086/595011] [4] Talbot GH, Bradley J, Edwards Jr JE, Gilbert D, Scheld M, Bartlett JG, Antimicrobial availability task force of the infectious diseases society of A. Bad bugs need drugs: An update on the development pipeline from the Antimicrobial availability task force of the infectious diseases society of America. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 2006;**42**(5):657-668 [PMID: 16447111 DOI:

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

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

97

[5] Antibiotics Resistance Threat in the US. US Department of Health & Human Services; Centers for Disease Control and Prevention [Internet]. 2013. Available from: http://www.

[6] President Advisory Council on Combating Antibiotic-resistant Bacteria. HHS. Gov. 2015. Available from: http://www.hhs.gov/ash/advisory.committees/paccarb/\$ [Accessed: March

[7] Detsis M, Karanika S, Mylonakis E. ICU acquisition rate, risk factors, and clinical significance of digestive tract colonization with extended-spectrum beta-lactamase-producing enterobacteriaceae: A systematic review and meta-analysis. Critical Care Medicine.

[8] Vardakas KZ, Rafailidis PI, Konstantelias AA, Falagas ME. Predictors of mortality in patients with infections due to multi-drug resistant Gram negative bacteria: The study, the patient, the bug or the drug? The Journal of Infection. 2013;**66**(5):401-414 [PMID:

[9] Munoz-Price LS, Poirel L, Bonomo RA, Schwaber MJ, Daikos GL, Cormican M, Cornaglia G, Garau J, Gniadkowski M, Hayden MK, Kumarasamy K, Livermore DM, Maya JJ, Nordmann P, Patel JB, Paterson DL, Pitout J, Villegas MV, Wang H, Woodford N, Quinn JP. Clinical epidemiology of the global expansion of *Klebsiella pneumoniae* carbapenemases. The Lancet Infectious Diseases. 2013;**13**(9):785-796 [PMID: 23969216 PMCID:

[10] Guh AY, Bulens SN, Mu Y, Jacob JT, Reno J, Scott J, Wilson LE, Vaeth E, Lynfield R, Shaw KM, Vagnone PM, Bamberg WM, Janelle SJ, Dumyati G, Concannon C, Beldavs Z, Cunningham M, Cassidy PM, Phipps EC, Kenslow N, Travis T, Lonsway D, Rasheed JK, Limbago BM, Kallen AJ. Epidemiology of carbapenem-resistant enterobacteriaceae in 7 US communities, 2012-2013. Journal of the American Medical Association.

[11] Spellberg B, Rex JH. The value of single-pathogen antibacterial agents. Nature Reviews Drug Discovery. 2013;**12**(12):963 [PMID: 24232373 PMCID: 4012226 DOI: 10.1038/

2015;**314**(14):1479-1487 [PMID: 26436831 DOI: 10.1001/jama.2015.12480]

2017;**45**(4):705-714. [PMID: 28157141 DOI: 10.1097/CCM.0000000000002253]

23142195 DOI: 10.1016/j.jinf.2012.10.028]

4673667 DOI: 10.1016/S1473-3099(13)70190-7]

cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf [Accessed: March 16, 2017]

10.1086/499819]

16, 2017]

nrd3957-c1]

In recent years, we have seen high-level resistance to last-line agents such as carbapenems. Inappropriate usage and a reduced antimicrobial pipeline have driven this crisis. Several companies are dedicated to the research and development of new antimicrobials for our armamentarium in combating multidrug-resistant organisms and preventing a preantibiotic era. Education will be vital across all healthcare disciplines, including to patients, as this will ultimately ensure optimal prescribing.
