Antibiotic Resistance and Novel Antibiotics for the Treatment of Urinary Tract Infections

Florian Wagenlehner

doi:10.14777/uti.2016.11.02.43

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Wagenlehner: Antibiotic Resistance and Novel Antibiotics for the Treatment of Urinary Tract Infections

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Urogenit Tract Infect 2016;11(2):43-48.

Published online: 19 January 2016

DOI: https://doi.org/10.14777/uti.2016.11.02.43

Antibiotic Resistance and Novel Antibiotics for the Treatment of Urinary Tract Infections

Florian Wagenlehner

Department of Urology, Paediatric Urology and Andrology, Justus-Liebig-University, Giessen, Germany

Correspondence to: Florian Wagenlehner http://orcid.org/0000-0002-2909-0797 Department of Urology, Paediatric Urology and Andrology, Justus-Liebig-University, Rudolf-Buchheim Strasse 7, D-35392 Giessen, Germany Tel: +49-641-985-44500, Fax: +49-641-985-44509 E-mail: wagenlehner@aol.com

Received 4 July 2016 Revised 4 July 2016 Accepted 16 July 2016

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

Surveillance data on antibiotic resistance need to be considered with respect to the origin of isolates, types of surveillance studies, and types of types of registered infections. Antibiotic resistance in gram-negative uropathogens has been investigated in both local and multinational studies. A compilation of worldwide studies for example showed resistance rates of gram-negative uropathogens against fluoroquinolones in 10% to 80%, against cephalosporines in 5% to 70% and against carbapenems in 0% to 35%. A specific surveillance study in the field of urology—the global prevalence of infections in urology (GPIU) study—is a point prevalence study with a global effort to create surveillance data in patients at various urological departments with health-care associated urogenital infections (HAUTIs). The GPIU study has been performed annually since 2003, with a total inclusion of 27,542 patients, thus far. Resistance rates of most uropathogens against all tested antibiotics were high, especially with multidrug resistance. A concerning finding was that the severity of HAUTI is also increasing—25% being urosepsis in recent years. In order to keep up with this alarming trend, novel antibiotics for the treatment of urinary tract infections need to be developed. Several strategies are currently employed: Beta-lactam/beta-lactamase inhibitor combinations are extended to cephalosporines and carbapenems. Novel fluroroquinolones have been developed, and so called siderophore antibiotics are being tested. Novel aminoglycosides and novel tetracyclines are also in the clinical development phases. Thus, several antibiotic substances are currently being developed, or in the late clinical phases of development.

Keywords: Urinary tract infections, Surveillance studies, Drug resistance, microbial, Novel antibiotics

REFERENCES

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Table 1.

Percent antibiotic resistance in healthcare-associated urinary tract infections in the global prevalence of infections in urology study between the years 2003 and 2010

Uropathogen	Aminopenicillin +BLI	Piperacillin tazobactam	Trimethoprim/ sulfamethoxazole	Ciprofloxacin	Cefuroxime	Cefotaxime	Ceftazidime	Imipenem	Gentamicin
Escherichia coli	50	25	48	45	33	28	29	3	30
Klebsiella spp.	64	40	62	57	63	57	51	2	46
Proteus spp.	42	15	55	30	26	27	30	2	31
Enterobacter spp.	63	40	52	42	66	47	48	4	48
Pseudomonas aeruginosa	Not tested	27	96	64	Not tested	Not tested	28	20	54
Enterococcus spp.	23	23	62	69	Not tested	Not tested	Not tested	25	73
CoNS	52	33	55	60	66	46	66	29	46
Staphylococcus aureus	57	46	26	54	35	35	22	41	18

Data from the article of Tandogdu et al. World J Urol 2014;32:790-801 [7].

BLI: beta-lactamase inhibitor, Spp.: species, CoNS: coagulase negative staphylococci.

Table 2.

Novel antibiotic substances for the treatment of complicated urinary tract infections and pyelonephritis

Antibiotic substance	Phase of development	Comparator agent in study	Antibacterial spectrum	Reference
Ceftolozane-tazobactam	Marketed	Levofloxacin	Gram-negatives	[9]
			Pseudomonas aeruginosa
			Class A, some Class C BL producing bacteria
Ceftazidime-avibactam	Marketed	Doripenem	Gram-negatives	[11,12]
			P. aeruginosa
			Class C, some Class D BL (ESBLs, KPCs, AmpC) producing bacteria
Imipenem relebactam	Phase three	Colistin	Gram-negatives	[14]
			P. aeruginosa
			Class C, some Class D BL (ESBLs, KPCs, AmpC) producing bacteria
Meropenem-vaborbactam	Phase three	Peperacillin tazobactam	Gram-negatives	[14]
			P. aeruginosa
			Class C, some Class D BL (ESBLs, KPCs, AmpC) producing bacteria
S-649266	Phase two	Imipenem	Gram-negatives	[14]
			P. aeruginosa
			Acinetobacter baumanii
			Class C, some Class D BL (ESBLs, KPCs, NDM) producing bacteria
BAL30072	Phase one	No comparator	Not tested clinically	[15]
Finafloxacin	Phase two	Ciprofloxacin	Gram-positives	[14]
			Gram-negatives
			P. aeruginosa
			Anaerobes Atypical bacteria
			Atypical bacteria
Plazomicin	Phase three	Meropenem	Selected gram-positives	[14]
			Gram-negatives (including aminoglycoside resistant)
			P. aeruginosa
			KPC, VIM, OXA BL producing bacteria
Eravacycline	Phase three	Levofloxacin	Gram-positives	[14]
			Gram-negatives
			A. baumanii

BL: beta-lactamases, ESBLs: extended spectrum -lactamases, KPCs: Klebsiella pneumoniae carbapenemases, AmpC: Class C -lactamase, NDM: New Delhi metallo--lactamase, VIM: Verona integron-encoded -lactamase, OXA: oxacillinase group -lactamase.

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