Cheol-In Kang

doi:10.4285/jkstn.2013.27.3.81

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Kang: What’s New in the Management of Bacterial Infections in the Era of Multidrug-Resistant Bacteria?

Review Article

J Korean Soc Transplant 2013;27(3):81-86.

Published online: 11 September 2013

DOI: https://doi.org/10.4285/jkstn.2013.27.3.81

What’s New in the Management of Bacterial Infections in the Era of Multidrug-Resistant Bacteria?

Cheol-In Kang, M.D.

Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

책임저자：강철인, 서울시 강남구 일원로 81 성균관대학교 의과대학 삼성서울병원 감염내과, 135-710 Tel: 02-3410-0324, Fax: 02-3410-0064 E-mail: collacin@hotmail.com 135-710 Tel: 02-3410-0324, Fax: 02-3410-0064 E-mail: collacin@hotmail.com

이 논문은 교육과학기술부의 재원으로 한국연구재단의 지원을 받아 수행된 기초연구사업임(No. 2010-0021572).

Received 22 August 201327 August 2013 Accepted 29 August 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Bacterial infection is an increasingly important diagnosis following successful organ transplantation in humans. This is notwithstanding the fact that opportunistic infections such as those of fungal and viral origin can occur frequently in this population. Infections due to multidrug resistant bacteria have been on the rise since the past decade and not surprisingly continue to challenge physicians. Recent studies show that rapidly increasing rates of infections in such population are due to methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and multidrug-resistant gram-negative bacilli. Furthermore, pan-drug-resistant infections are now on the rise, especially in gram-negative bacilli. Regrettably, our therapeutic options for these pathogens are currently extremely limited. Very recently, it has been shown that infections due to Clostridium difficile spp. have been the leading cause of antibiotic-associated diarrhea. It is a well-known fact that infections due to antimicrobial-resistant bacteria were associated with a greater likelihood of inappropriate antimicrobial therapy. Therefore, it is very clear that inappropriate antimicrobial therapy has an adverse effect on survival rate in patients with serious infections. This is especially true in immunocompromised hosts. Hence, in the light of the above, it is very essential that physicians who are treating immunocompromised patients should be aware of not only current epidemiological status of antimicrobial resistance but also proper clinical practice guidelines to be followed while diagnosing infections due to such antimicrobial agents. The objective of this review is, therefore, to provide a recent update of currently available antimicrobial therapeutic strategies for life-threatening infections due to antimicrobial-resistant pathogens.

Keywords: Bacterial infections, Antimicrobial resistance, Antimicrobial agents

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Table 1.

Recommendations for the antimicrobial treatment of MRSA infections

Manifestation	Treatment	Adult dose
Skin and soft tissue infection (SSTI)
Purulent cellulitis	Clindamycin	300∼450 mg PO TID
	TMP-SMX	2∼4 T PO BID
	Doxycycline or minocycline	100 mg PO BID
Complicated SSTI	Vancomycin	15∼20 mg/kg IV every 8∼12 hr
	Linezolid	600 mg PO/IV BID
	Clindamycin	600 mg IV TID
Bacteremia and infective endocarditis	Vancomycin	15∼20 mg/kg IV every 8∼12 hr
Pneumonia	Vancomycin	15∼20 mg/kg IV every 8∼12 hr
	Linezolid	600 mg PO/IV BID
	Clindamycin	600 mg IV TID
Bone and joint infections	Vancomycin	15∼20 mg/kg IV every 8∼12 hr
	Linezolid	600 mg PO/IV BID
	Clindamycin	600 mg IV TID
	TMP-SMX	5 mg/kg/dose PO/IV every 8∼12 hr

Abbreviations: MRSA, Methicillin-resistant Staphylococcus aureus ; TMP-SMX, Trimethoprim/sulfamethoxazol; BID, twice a day; TID, three times a day; IV, intravenous; PO, per os.

Adapted from Table 3 of reference [3].

Table 2.

Antimicrobial therapy for serious infections caused by MDR-Klebsiella pneumoniae or Escherichia coli

Antimicrobial agents	Dose	Adverse drug reaction	Commentary
For ESBL or AmpC producers
Imipenem/cilastatin	0.5 g IV q 6 hr	CNS toxicity
Meropenem	1 g IV q 8 hr		Preferred in patients with neurologic disorder
Doripenem	0.5 g IV q 8 hr
Ertapenem	1 g IV q 24 hr		Long half-life
For carbapenem-resistant
Enterobacteriaceae
Colistin (polymyxin E)	Mild infection: 5 mg/kg per day, divided into 2 doses	Nephrotoxicity, neurotoxicity	Available in colistimethate sodium salt
	Severe infection: 3.5×[(1.5× CrCln)＋30]=total daily dose		The maximum suggested daily dose is 475 mg
Tigecycline	After 100 mg IV loading, 50 mg IV q 12 hr	Nausea, vomiting, hepatotoxicity	Approved for complicated intra-abdominal infection and soft tissue infections

Abbreviations: MDR, multidrug-resistant; ESBL, extended-spectrum β-lactamase; CNS, central nervous system; CrCln, creatinine clearance normalized for body surface area; IV, intravenous.

Adapted from Table 1 of reference [11].

Table 3.

Antimicrobial therapy for serious infections caused by carbapenem-resistant-Pseudomonas aeruginosa or Acinetobacter baumannii ^a

Antimicrobial agents	Dose	Adverse drug reaction	Commentary
Colistin (polymyxin E)	Mild infection: 5 mg/kg per day, divided into 2 doses	Nephrotoxicity, neurotoxicity	Available in colistimethate sodium salt
	Severe infection: 3.5×[(1.5× CrCln)＋30]=total daily dose		The maximum suggested daily dose is 475 mg
Aztreonam	2 g IV q 8∼6 hr		Some isolates may be susceptible to aztreonam
Amikacin	7.5 mg/kg IV q 12 hr	Nephrotoxicity, ototoxicity	Combination with other susceptible antibiotics
Tobramycin	1.7 mg/kg IV q 8 hr	Nephrotoxicity, ototoxicity	Combination with other susceptible antibiotics

Adapted from Table 2 of reference [11].

^a Carbapenem-resistant-Pseudomonas aeruginosa or Acinetobacter baumannii isolates might be susceptible to other classes of antibiotics (e.g., cefepime, piperacillin/tazobactam, and ciprofloxacin), particularly in isolates with porinmutation as the main mechanism of carbape-nem resistance. In such cases, those antibiotics susceptible in vitro can be used.

Table 4.

Suggested approaches to therapy for Clostridium difficile infection

Category	Antimicrobial therapy
Initial episode
Mild-to-moderate infection	Metronidazole at a dose of 500 mg orally 3 times daily for 10∼14 days
Severe infection or unresponsiveness to or intolerance of metronidazole	Vancomycin at a dose of 125 mg orally 4 times daily for 10∼14 days
First recurrence
Mild-to-moderate infection	Metronidazole at a dose of 500 mg orally 3 times daily for 10∼14 days
Severe infection or unresponsiveness to or intolerance of metronidazole	Vancomycin at a dose of 125 mg orally 4 times daily for 10∼14 days
Second recurrence	Vancomycin in tapered and pulsed doses
Third recurrence	Vancomycin at a dose of 125 mg orally 4 times daily for 14 days, followed by rifaximinat a dose of 400 mg twice daily for 14 days
Other options for recurrent infection	Intravenous immune globulin at a dose of 400 mg per kg of body weight once every 3 weeks for a total of 2 or 3 doses
	Therapy with other microorganisms, including fecal transplantation

Adapted from Table 2 of reference [17].

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