Evaluation of a Double-Disk Synergy Test with a Common Metallo-^|^beta;-Lactamase Inhibitor, Mercaptoacetate, for Detecting NDM-1-Producing Enterobacteriaceae and Acinetobacter baumannii

2014 ◽  
Vol 67 (1) ◽  
pp. 66-68 ◽  
Author(s):  
Jun-ichi Wachino ◽  
Mari Matsui ◽  
Hoang Huy Tran ◽  
Masato Suzuki ◽  
Satowa Suzuki ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Beta Lactamase ◽  
Synergy Test ◽  
Lactamase Inhibitor

scholarly journals Gambaran Infeksi Acinetobacter baumannii dan Pola Sensitifitasnya terhadap Antibiotik

Sari Pediatri ◽  
2016 ◽  
Vol 16 (1) ◽  
pp. 35
Author(s):  
I Wayan Gustawan ◽  
Hindra Irawan Satari ◽  
Idham Amir ◽  
Dalima AW Astrawinata
Keyword(s):  
Acinetobacter Baumannii ◽  
Beta Lactamase ◽  
Lactamase Inhibitor

Latar belakang. Adanya peningkatan insiden infeksi Acinetobacter baumannii yang disertai peningkatan kejadian resistensi antibiotik, peningkatan morbiditas dan mortalitas, dan terbatasnya laporan kejadian infeksi bakteri ini pada pasien anak.Tujuan. Mengetahui gambaran infeksi Acinetobacter baumannii dan pola sensitifitasnya terhadap antibiotik di Departemen Ilmu Kesehatan Anak RSUPN Dr Cipto Mangunkusumo.Metode. Merupakan penelitian deskriptif retrosfektif melalui penelusuran data hasil biakan darah di laboratorium dan rekam medis dari Januari-Desember 2012.Hasil. Didapatkan 47 isolat darah Acinetobacter baumannii dari 32 pasien. Penelusuran rekam medis mendapatkan 24 data pasien lengkap. Semuanya merupakan pasien ruang NICU, sebagian besar laki-laki (18/24) dan neonatus kurang bulan (18/24). Gambaran klinis menunjukkan rerata frekuensi denyut jantung 148 kali/menit, frekuensi napas 55 kali/menit, suhu aksila 37,10C, kadar leukosit 12767,8/mm3, kadar trombosit 58491,3/mm3, kadar procalcitonin 17,6 ng/mL, dan CRP 88,5 mg/L. Rerata lama perawatan sebelum terjadi infeksi 23,9 hari. Sebagian besar pasien menggunakan alat medis seperti ventilator, CPAP, jalur vena sentral, jalur vena perifir, dan pipa nasogastrik dengan rerata lama pemakaian masing-masing 17,9, 4,5, 20,9, 13,3, dan 17,3 hari. Semua pasien mendapat antibiotik sebelum infeksi dengan rerata lama pemberian 22,5 hari. Uji kepekaan antibiotik mendapatkan 23 isolat (23/24) merupakan MDR. Resistensi antibiotik didapatkan pada golongan aminoglikosida, carbapenem, quinolon, sefalosporin, penisilin-beta lactamase inhibitor, dan tigesiklin. Sebagian besar penderita meninggal dalam perawatan (18/24).Kesimpulan. Semua pasien yang menderita infeksi Acinetobacter baumannii dirawat di ruang NICU, sebagian besar pasien merupakan kasus MDR.

scholarly journals Activities of beta-lactams against Acinetobacter genospecies as determined by agar dilution and E-test MIC methods.

1997 ◽  
Vol 41 (4) ◽  
pp. 767-770 ◽  
Author(s):  
M A Visalli ◽  
M R Jacobs ◽  
T D Moore ◽  
F A Renzi ◽  
P C Appelbaum
Keyword(s):  
Acinetobacter Baumannii ◽  
Acinetobacter Calcoaceticus ◽  
Beta Lactamase ◽  
Beta Lactams ◽  
Acinetobacter Junii ◽  
Acinetobacter Radioresistens ◽  
Amoxicillin Clavulanate ◽  
Agar Dilution ◽  
Acinetobacter Haemolyticus ◽  
Lactamase Inhibitor

The agar dilution MIC method was used to test activities of ticarcillin, ticarcillin-clavulanate, amoxicillin, amoxicillin-clavulanate, ampicillin, ampicillin-sulbactam, piperacillin, piperacillin-tazobactam, inhibitors alone, ceftazidime, and imipenem against 237 Acinetobacter genospecies. A total of 93.2% of strains were beta-lactamase positive by the chromogenic cephalosporin method. Overall, ampicillin-sulbactam was the most active combination against all strains (MIC at which 50% of the isolates are inhibited [MIC50] and MIC90, 4.0 and 32.0 microg/ml; 86.9% susceptible at < or = 16 microg/ml), followed by ticarcillin-clavulanate (16.0 and 128.0 microg/ml; 85.7% susceptible at < or = 64 microg/ml), piperacillin-tazobactam (16.0 and 128.0 microg/ml; 84.8% susceptible at < or = 64 microg/ml), and amoxicillin-clavulanate (16.0 and 64.0 microg/ml; 54.4% susceptible at < or =16 microg/ml). Ceftazidime and imipenem yielded MIC50s and MIC90s of 8.0 and 64.0 microg/ml (ceftazidime) and 0.5 and 1.0 microg/ml (imipenem), respectively; 71.3% of strains were susceptible to ceftazidime at < or = 16 microg/ml, and 99.2% were susceptible to imipenem at < or = 8 microg/ml. Sulbactam was the most active beta-lactamase inhibitor alone (MIC50 and MIC90, 2.0 and 16.0 microg/ml); clavulanate and tazobactam were less active (16.0 and 32.0 microg/ml for both compounds). Enhancement of beta-lactams by beta-lactamase inhibitors was not always seen in beta-lactamase-positive strains, and activity of combinations such as ampicillin-sulbactam was due to the inhibitor alone. Acinetobacter baumannii was the most resistant genospecies. By contrast, Acinetobacter haemolyticus, Acinetobacter calcoaceticus, Acinetobacter johnsonii, Acinetobacter junii, Acinetobacter radioresistens, and other non-Acinetobacter baumannii strains were more susceptible to all compounds tested. E-test MICs were within 1 dilution of agar dilution MICs in 38.4 to 89.6% of cases and within 2 dilutions in 61.6 to 98.6% of cases.

scholarly journals In Vitro Activity of the Ultra-Broad-Spectrum Beta-Lactamase Inhibitor QPX7728 in Combination with Meropenem against Clinical Isolates of Carbapenem-Resistant Acinetobacter baumannii

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Kirk Nelson ◽  
Debora Rubio-Aparicio ◽  
Ruslan Tsivkovski ◽  
Dongxu Sun ◽  
Maxim Totrov ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Broad Spectrum ◽  
Wide Distribution ◽  
Clinical Isolates ◽  
Beta Lactamase ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Substrate Inhibitor ◽  
Lactamase Inhibitor

ABSTRACT QPX7728 is a recently discovered ultra-broad-spectrum beta-lactamase inhibitor (BLI) with potent inhibition of key serine and metallo-beta-lactamases. QPX7728 enhances the potency of many beta-lactams, including carbapenems, in beta-lactamase-producing Gram-negative bacteria, including Acinetobacter spp. The potency of meropenem alone and in combination with QPX7728 (1 to 16 μg/ml) was tested against 275 clinical isolates of Acinetobacter baumannii (carbapenem-resistant A. baumannii [CRAB]) collected worldwide that were highly resistant to carbapenems (MIC50 and MIC90 for meropenem, 64 and >64 μg/ml). Addition of QPX7728 resulted in a marked concentration-dependent increase in meropenem potency, with the MIC90 of meropenem alone decreasing from >64 μg/ml to 8 and 4 μg/ml when tested with fixed concentrations of QPX7728 at 4 and 8 μg/ml, respectively. In order to identify the mechanisms that modulate the meropenem-QPX7728 MIC, the whole-genome sequences were determined for 135 isolates with a wide distribution of meropenem-QPX7728 MICs. This panel of strains included 116 strains producing OXA carbapenemases (71 OXA-23, 16 OXA-72, 16 OXA-24, 9 OXA-58, and 4 OXA-239), 5 strains producing NDM-1, one KPC-producing strain, and 13 strains that did not carry any known carbapenemases but were resistant to meropenem (MIC ≥ 4 μg/ml). Our analysis indicated that mutated PBP3 (with mutations localized in the vicinity of the substrate/inhibitor binding site) is the main factor that contributes to the reduction of meropenem-QPX7728 potency. Still, >90% of isolates that carried PBP3 mutations remained susceptible to ≤8 μg/ml of meropenem when tested with a fixed 4 to 8 μg/ml of QPX7728. In the absence of PBP3 mutations, the MICs of meropenem tested in combination with 4 to 8 μg/ml of QPX7728 did not exceed 8 μg/ml. In the presence of both PBP3 and efflux mutations, 84.6% of isolates were susceptible to ≤8 μg/ml of meropenem with 4 or 8 μg/ml of QPX7728. The combination of QPX7728 with meropenem against CRAB isolates with multiple resistance mechanisms has an attractive microbiological profile.

scholarly journals Detection of metallo beta lactamase production in imipenem resistant gram negative bacilli non fermenters isolated in a Tertiary Care Hospital.

2019 ◽  
Vol 26 (12) ◽  
pp. 2080-2084
Author(s):  
Ayesha Sajjad ◽  
Muna Malik ◽  
Iffat Javed ◽  
Sohaila Mushtaq ◽  
Fareeha Imran ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Tertiary Care ◽  
Care Hospital ◽  
Beta Lactamase ◽  
Culture Methods ◽  
Cross Sectional ◽  
Gram Negative ◽  
Synergy Test ◽  
Pseudomonas Luteola

Objectives: Metallo-beta lactamase (MBL) producing non fermenter Gram negative bacilli is an emerging warning and cause of worry as they have established as one of the most feared resistance mechanisms and are the foremost cause of nosocomial infections worldwide. Carbapenem, including Imipenem, Meropenem and Doripenem are often used as a last remedy for treatment of infections caused by Pseudomonas aeruginosa, Acinetobacter and other Gram-negative. The present study was designed to explore the distribution of imipenem resistant non-fermenter Gram-negative bacilli isolates in different age groups. Study Design: Cross sectional Descriptive study. Setting: Microbiology laboratory, PGMI, Lahore. Period: January 2015 to December 2015. Material & Methods: 53 imipenem resistant NFGNB that were isolated from appropriate sampling of patients suffering from several infections were analyzed by using different standard microbiological techniques like microscopy, culture methods, biochemical reactions and antibiotic susceptibility using Kirby-Bauer method. MBL recognition was performed by imipenem-2MPA double disc synergy test (DDST). Results: This study shows the frequency of imipenem resistant non-fermenter Gram-negative bacilli isolated from various clinical wards. Maximum NFGNB were recovered from surgery/surgical allied 35.84% followed by ICU 28.3%, medicine /medicine allied 20.75%, pediatrics 9.4% and gynae/obs 5.6% respectively. MBL production was identified among different imipenem resistant non-fermenter Gram-negative bacilli isolates by DDST using 2-MPA. Out of total 53 imipenem resistant non-fermenter Gram Negative Bacilli 37 Pseudomonas aeruginosa 20(54.05%) were MBL positive. Out of 13 Acinetobacter baumannii and 2 Pseudomonas luteola, 11(84.61%) Acinetobacter baumannii and 1(50%) Pseudomonas luteola were positive for MBL production. None of the Acinetobacter junii indicated MBL production. Conclusion: Double disc synergy test is operational for detection of MBL producers among NFGNB. It can be established in our routine clinical microbiology laboratories, for the MBL recognition especially in imipenem resistant isolates as of its cost efficiency.

scholarly journals Impact of Intrinsic Resistance Mechanisms on Potency of QPX7728, a New Ultrabroad-Spectrum Beta-Lactamase Inhibitor of Serine and Metallo-Beta-Lactamases in Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Olga Lomovskaya ◽  
Kirk Nelson ◽  
Debora Rubio-Aparicio ◽  
Ruslan Tsivkovski ◽  
Dongxu Sun ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Resistance Mechanisms ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Intrinsic Resistance ◽  
Content Type ◽  
Beta Lactamases ◽  
Beta Lactam Antibiotics ◽  
Lactamase Inhibitor

ABSTRACT QPX7728 is an ultrabroad-spectrum boronic acid beta-lactamase inhibitor that demonstrates inhibition of key serine and metallo-beta-lactamases at a nanomolar concentration range in biochemical assays with purified enzymes. The broad-spectrum inhibitory activity of QPX7728 observed in biochemical experiments translates into enhancement of the potency of many beta-lactams against strains of target pathogens producing beta-lactamases. The impacts of bacterial efflux and permeability on inhibitory potency were determined using isogenic panels of KPC-3-producing isogenic strains of Klebsiella pneumoniae and Pseudomonas aeruginosa and OXA-23-producing strains of Acinetobacter baumannii with various combinations of efflux and porin mutations. QPX7728 was minimally affected by multidrug resistance efflux pumps either in Enterobacteriaceae or in nonfermenters, such as P. aeruginosa or A. baumannii. Against P. aeruginosa, the potency of QPX7728 was further enhanced when the outer membrane was permeabilized. The potency of QPX7728 against P. aeruginosa was not affected by inactivation of the carbapenem porin OprD. While changes in OmpK36 (but not OmpK35) reduced the potency of QPX7728 (8- to 16-fold), QPX7728 (4 μg/ml) nevertheless completely reversed the KPC-mediated meropenem resistance in strains with porin mutations, consistent with the lesser effect of these mutations on the potency of QPX7728 compared to that of other agents. The ultrabroad-spectrum beta-lactamase inhibition profile, combined with enhancement of the activity of multiple beta-lactam antibiotics with various sensitivities to the intrinsic resistance mechanisms of efflux and permeability, indicates that QPX7728 is a useful inhibitor for use with multiple beta-lactam antibiotics.

scholarly journals Importance of beta-lactamase inhibitor pharmacokinetics in the pharmacodynamics of inhibitor-drug combinations: studies with piperacillin-tazobactam and piperacillin-sulbactam.

1997 ◽  
Vol 41 (4) ◽  
pp. 721-727 ◽  
Author(s):  
P D Lister ◽  
A M Prevan ◽  
C C Sanders
Keyword(s):  
Antibacterial Activity ◽  
Critical Concentration ◽  
Specific Inhibitor ◽  
Logarithmic Phase ◽  
Critical Ratio ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Dosing Regimens ◽  
Lactamase Inhibitor

An in vitro pharmacokinetic model was used to study the pharmacodynamics of piperacillin-tazobactam and piperacillin-sulbactam against gram-negative bacilli producing plasmid-encoded beta-lactamases. Logarithmic-phase cultures were exposed to peak antibiotic concentrations observed in human serum after the administration of intravenous doses of 3 g of piperacillin and 0.375 g of tazobactam or 0.5 g of sulbactam. Piperacillin and inhibitor were either dosed simultaneously or piperacillin was dosed sequentially 0.5 h after dosing with the inhibitor. In studies with all four test strains, the pharmacodynamics observed after simultaneous dosing were similar to those observed with the sequential regimen. Since the ratio between piperacillin and tazobactam was in constant fluctuation after sequential dosing, these data suggest that the pharmacodynamics of the piperacillin-inhibitor combinations were not dependent upon maintenance of a critical ratio between the components. Furthermore, when regrowth was observed, the time at which bacterial counts began to increase was similar between the simultaneous and sequential dosing regimens. Since the pharmacokinetics of the inhibitors were the same for all regimens, these data suggest that the length of time that the antibacterial activity was maintained over the dosing interval with these combinations was dictated by the pharmacokinetics of the beta-lactamase inhibitor in the combination. The antibacterial activity of the combination appeared to be lost when the amount of inhibitor available fell below some critical concentration. This critical concentration varied depending upon the type and amount of enzyme produced, as well as the specific inhibitor used. These results indicate that the antibacterial activity of drug-inhibitor combinations, when dosed at their currently recommended ratios, is more dependent on the pharmacokinetics of the inhibitor than on those of the beta-lactam drug.

Orally effective acid prodrugs of the .beta.-lactamase inhibitor sulbactam

1990 ◽  
Vol 33 (1) ◽  
pp. 344-347 ◽  
Author(s):  
Arthur R. English ◽  
Dennis Girard ◽  
V. John Jasys ◽  
Robert J. Martingano ◽  
Michael S. Kellogg
Keyword(s):  
Beta Lactamase ◽  
Lactamase Inhibitor
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