Antibacterial effect evaluation of moxalactam against extended-spectrum &beta;-lactamase-producing <em>Escherichia coli</em> and <em>Klebsiella pneumoniae </em>with in vitro pharmacokinetics/pharmacodynamics simulation

Abstract

ObjectivesThe aim of this study was to evaluate the bactericidal effects of moxalactam (MOX), cefotaxime (CTX), and cefoperazone/sulbactam (CFZ/SBT) against extended-spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae, using an in vitro pharmacokinetics (PK)/pharmacodynamics model.MethodsTwo clinical ESBL-producing strains (blaCTX-M-15 positive E. coli 3376 and blaCTX-M-14 positive K. pneumoniae 2689) and E. coli American Type Culture Collection (ATCC)25922 were used in the study. The PK Auto Simulation System 400 was used to simulate the human PK procedures after intravenous administration of different doses of MOX, CTX, and CFZ/SBT. Bacterial growth recovery time (RT) and the area between the control growth curve and bactericidal curves (IE) were employed to assess the antibacterial efficacies of all the agents.ResultsThe minimum inhibitory concentrations of MOX, CTX, and CFZ/SBT against E. coli ATCC25922, 3376, and 2689 strains were 0.5, 0.5, 0.25; 0.06, >256, 256; and 0.5/0.5, 16/16, 32/32 mg/L. All the agents demonstrated outstanding bactericidal effects against E. coli ATCC25922 (RT >24 h and IE >120 log10 CFU/mL·h−1) with simulating PK procedures, especially in the multiple dose administration models. Against ESBL producers, CTX and CFZ/SBT displayed only weak bactericidal effects, and subsequent regrowth was evident. MOX exhibited potent antibacterial activity against all the strains tested. The values of effective parameters of MOX were much higher than those of CTX and CFZ/SBT (the bacterial RTs with the 3 agents were >24, <4, and <13 h, and the IEs were >110, <10, and <60 log10 CFU/mL·h−1, respectively).ConclusionMOX demonstrated excellent bactericidal effect, which is worthy of further exploration to serve as an alternative therapeutic agent against ESBL-producing Enterobacteriaceae.

<p>Simulating moxalactam dosage for extended-spectrum β-lactamase-producing <em>Enterobacteriaceae</em> using blood antimicrobial surveillance network data</p>

“…Against isolates with high MICs (4, 8, and 16 mg/L), MCS of CFZ/SBT simulated regimens failed to reach 90% PTA. Moreover, our previous in vitro PK/PD study demonstrated that regimens of CFZ/SBT (2 g iv q8h) against ESBL producers with high MICs failed to maintain effective killing, and allowed significant regrowth 37. FEP was relatively stable against ESBL compared with third-generation cephalosporins.…”

Moxalactam is not more active on extended spectrum&nbsp;<br /><span style="text-align: justify">&beta;</span>-lactamase (ESBL) producing bacteria than on non-ESBL producers

“…The analysis ( Figure 1 ) revealed that conclusions drawn earlier 1 , 2 on the basis of a study on a few strains may not be valid. My analysis revealed that of the 3,242 bacteria tested in our laboratory, using Clinical and Laboratory Standards Institute 3 guidelines, 50.6% were identified as ESBL producers.…”

“…In a recently published article 1 moxalactam has been claimed to be very effective on extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae , concluding “MOX demonstrated excellent bactericidal effect, which is worthy of further exploration to serve as an alternative therapeutic agent against ESBL-producing Enterobacteriaceae”. Similar claims have also been made earlier.…”

“…We thank Dr Singh for his comments on our recently published article. 1 We are in favor of his view, “observations on a few strains should not be used to draw a generalized statement”. As we mentioned, moxalactam (MOX) is worthy of further exploration to serve as an alternative therapeutic agent against extended-spectrum β-lactamase (EBSL)-producing Enterobacteriaceae.…”

Prevalence and Antimicrobial Resistance Pattern of Extended Spectrum Beta Lactamase Producing Gram Negative Bacterial Isolates Obtained From Various Clinical Samples of Indoor Patients Admitted in a Tertiary Care Hospital

“…2,3 Thus, the prudent use of antimicrobials is as crucial as finding alternatives of carbapenems to treat the infections caused by ESBLproducing isolates and avoid exacerbation of the spreading of ESBLs. 4 When detecting ESBL-positive strains, microbiology laboratories should provide the clinician with reliable therapeutic options for successfully treating infected patients, since ESBL-distribution has been shown to differ among countries. 5 Inadequate surveillance practices and inefficient regulatory system play a key role in the determination of antimicrobial resistance.…”