A Case Report
Maria Teressa, Yongkie Iswandi Purnama, Soroy Lardo
Division of Tropical and Infectious Disease, Department of Internal Medicine, Gatot Soebroto Presidential Central Army Hospital, Jakarta, Indonesia
Received: 12 Jan. 2022; Accepted: 14 Jul. 2022
Abstract
Diagnosis; and management of retroperitoneal abscesses caused by ESBL (Extended-Spectrum-βetaLactamase) Escherichia Coli require special attention.
A female patient came to the Emergency Department with complaints of abdominal discomfort, bloating, nausea, fever, and urination pain for 1 week, and a physical examination demonstrated an enlarged mass in the left flank for the past 6 months.
Laboratory results showed an increase in leukocytes and procalcitonin; hence the antibiotic cefoperazone sulbactam was given as empirical therapy.
An abdominal CT scan revealed multiple retroperitoneal abscesses in the left and right hemiabdomen; therefore, levofloxacin and metronidazole were given as additional antibiotics.
Percutaneous abscess drainage was performed and from the pus culture obtained grew ESBL Escherichia Coli bacteria. Furthermore, antibiotics were changed to intravenous amikacin according to the results of the susceptibility test. The patient’s clinical symptoms improved significantly, and she was discharged and evaluated in the outpatient clinic.
Extended Spectrum Beta Lactamase (ESBL)
ESBL is a broad-spectrum enzyme produced most characteristically by E. coli, Klebsiella, and Proteus species. Enzymes develop based on amino acid changes in beta-lactamase
The mechanism of resistance occurs in the bacterial cell wall, the location of the binding site, and the presence of enzyme modification with further stages of impermeability and destruction of antibiotics by beta-lactamase
The three most representative mechanisms of resistance to beta-lactam antibiotics in gram-negative bacteria are the destruction of antibiotics by beta-lactamase, i.e., impermeability, closure of porin channels in the bacterial cell wall (most important as a mechanism of resistance to carbapenems for Pseudomonas- aeruginosa) and extrusion of antibiotics by an efflux pump which may cause resistance to several classes of antibiotics.
The mechanism of action and resistance of beta-lactams lies in the bacterial cell wall with binding sites and modifying enzymes of other classes of antibiotics at the intracellular level. ESBL is a broad-spectrum enzyme produced by E. coli, Klebsiella, and Proteus species. The occurrence of resistance to the presence of enzymes that develop based on changes in one amino acid in Beta-lactamase.
Due to minimal structural changes, ESBLs have the capacity to inactivate some broad-spectrum beta-lactam antibiotics. Knowledge of the variability of these mechanisms of action and resistance can contribute to the decision and selection of antimicrobial therapy for resistant organisms.
Based on the amino acid enzymes’ clinically relevant properties, ESBLs represent a classic resistance mechanism, where in vitro susceptibility may not consistently predict clinical efficacy. Due to minimal structural changes, ESBLs can inactivate some broad-spectrum beta-lactam antibiotics.
The Use of third-generation cephalosporins and fluoroquinolones has been identified as a risk factor for ESBLs. In contrast to ESBLs-mediated plasmid production, the most classical AmpC Beta-lactamase is mediated and occurs in important ICU pathogens such as Enterobacter and p. aeruginosa. In recent years, plasmid-mediated ampC beta-lactamase has been identified in pathogens E. coli and K pneumonia.
ESBL is related to genetic development and functional diversity. The beta-lactam group has an excellent safety profile and a broad antimicrobial spectrum as a therapeutic class in humans and animals. Their use causes a permanent selective force that drives the resistance diversification mechanism.
Resistance to β-lactams increases rapidly in the presence of new β-lactamase enzymes that degrade β-lactams. The appearance of this β-lactamase spectrum can deactivate most of the cephalosporins. The complexity and diversity of ESBLs is increasing rapidly, so more than 170 variants have been described with a single genotype, ESBL encoding CTMX.
The mechanism of bacterial resistance to β-lactam antibiotics appears when antibiotics or antimicrobials effectively eradicate pathogens with the initiation of bacteria surviving with higher doses of antibiotics. When antibiotics cannot kill pathogens, it is a sign of treatment failure, even for organisms resistant to more than one antibiotic.
Carrier proteins in the cytoplasmic membrane, which are capable of capturing molecules located in the membrane or cytoplasm, are associated with accessory proteins that are linked in turn with channel proteins of the outer membrane. Although antimicrobial efflux is the most common model of acquired resistance to tetracyclines, there is a growing pattern of resistance to other drugs, including β lactams.
In the last decade, ESBL has become a concern of the scientific community with the existence of plasmids capable of hydrolyzing oxyimino-cephalosporins (3rd and 4th generation cephalosporins) and monobactams. In addition, some antibiotics such as clavulanic acid, sulbactam and tazobactam are susceptible to β-lactamase. The previous definition of ESBL was classically a TEM-1, TEM-2, or SHV derivative.
Klasifikasi terbaru ESBL terdiri dari; 1) ESBLs klas A, terdiri dari ESBL dan CTX-M (paling sering ditemukan), enzim SHV dan TEM. Enzim-enzim ini sebagian besar dapat ditransfer secara horizontal dan dapat dinonaktifkan atau dihambat oleh asam klavulanat.; 2) ESBLM (Micellaneous) dibagi menjadi ESBLM-C (Kelas C, AmpC yang dimediasi plasmid) dan ESBLM-D (kelas D). Amp C didapat dan ESBL paling sering ditemukan di kelas ini; 3) ESBL CARBA (ESBL yang mendegradasi karbapenem) dibagi menjadi ESBL CARBA-A, ESBL CARBA-B dan ESBL CARBA-D. ESBL sering didapatkan pada plasmid besar disamping gen resistensi lain yang memberikan resistensi terhadap antimikroba seperti aminglikosida dan sulfonamide.
The latest ESBL classification consists of; 1) ESBLs class A, ESBL, and CTX-M (most commonly found), SHV, and TEM enzymes. These enzymes are predominantly horizontally transferable and can be inactivated or inhibited by clavulanic acid.; 2) ESBLM (Miscellaneous) is divided into ESBLM-C (Class C, plasmid-mediated AmpC) and ESBLM-D (class D). C amp gains and ESBLs are most commonly found in this class; 3) ESBL CARBA (ESBL that degrades carbapenems) is divided into ESBL CARBA-A, ESBL CARBA-B, and ESBL CARBA-D. ESBL is often found in large plasmids and other resistance genes confer resistance to antimicrobials such as aminoglycosides and sulfonamides.