Effect of the Inoculum Size on Carbapenem Susceptibilities of β-Lactamase-Negative, Ampicillin-Resistant Haemophilus influenzae

Miyazaki, Hiroo; Horii, Toshinobu; Nagura, Osanori; Suda, Takafumi; Chida, Kingo; Nakamura, Hirotoshi

doi:10.1007/s00284-008-9259-9

Cited by 3 publications

(5 citation statements)

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“…For example, aminopenicillins displayed an in vitro inoculum effect against b-lactamase-producing isolates of H. influenzae and also b-lactamase-deficient isolates of H. influenzae that were resistant to ampicillin. 92 The in vitro inoculum effect mediated by the b-lactamase-deficient isolates of H. influenzae was likely due to mutations in the protein targets of the aminopenicillins. Increasing the density of bacteria in an in vitro system will also likely decrease the average number of b-lactam molecules available to interact with a bacterial cell.…”

Section: Discussionmentioning

confidence: 99%

“…The inoculum effect of b-lactams against H. influenzae has been studied exclusively in the context of in vitro susceptibility testing or time-kill analyses. Substantial in vitro inoculum effects were noted for aminopenicillins [82][83][84][85][86][87] and cephalosporins, 81,84,86,[88][89][90][91] whereas carbapenems 87,92 and cefoxitin 88 were only evaluated in a few studies and did not demonstrate a substantial inoculum effect in vitro (Table 4). Two studies detected an in vitro inoculum effect for aminopenicillins against b-lactamase-producing strains of H. influenzae but did not observe an inoculum effect in b-lactamase-deficient strains.…”

Section: H Influenzaementioning

confidence: 99%

“…81,84,86,88,89,91 In addition, b-lactamase-deficient strains of H. influenzae that were resistant to ampicillin mediated an in vitro inoculum effect during susceptibility testing of carbapenems, cephalosporins and aminopenicillins. 90,92 The authors attributed the ampicillin resistance and inoculum effects to mutations in the PBP3 enzyme that decrease the target affinities of cephalosporins and other b-lactams. Regardless of the mechanisms behind the in vitro inoculum effects observed for H. influenzae, there were no animal models or human studies to indicate that the in vitro inoculum effects observed for cephalosporins and aminopenicillins are clinically significant.…”

Section: H Influenzaementioning

confidence: 99%

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Inoculum effect of β-lactam antibiotics

Lenhard

Bulman

2019

Journal of Antimicrobial Chemotherapy

102

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The phenomenon of attenuated antibacterial activity at inocula above those utilized for susceptibility testing is referred to as the inoculum effect. Although the inoculum effect has been reported for several decades, it is currently debatable whether the inoculum effect is clinically significant. The aim of the present review was to consolidate currently available evidence to summarize which β-lactam drug classes demonstrate an inoculum effect against specific bacterial pathogens. Review of the literature showed that the majority of studies that evaluated the inoculum effect of β-lactams were in vitro investigations of Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Haemophilus influenzae and Staphylococcus aureus. Across all five pathogens, cephalosporins consistently displayed observable inoculum effects in vitro, whereas carbapenems were less susceptible to an inoculum effect. A handful of animal studies were available that validated that the in vitro inoculum effect translates into attenuated pharmacodynamics of β-lactams in vivo. Only a few clinical investigations were available and suggested that an in vitro inoculum effect of cefazolin against MSSA may correspond to an increased likeliness of adverse clinical outcomes in patients receiving cefazolin for bacteraemia. The presence of β-lactamase enzymes was the primary mechanism responsible for an inoculum effect, but the observation of an inoculum effect in multiple pathogens lacking β-lactamase enzymes indicates that there are likely multiple mechanisms that may result in an inoculum effect. Further clinical studies are needed to better define whether interventions made in the clinic in response to organisms displaying an in vitro inoculum effect will optimize clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: H Influenzaementioning

confidence: 99%

Section: H Influenzaementioning

confidence: 99%

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Inoculum effect of β-lactam antibiotics

Lenhard

Bulman

2019

Journal of Antimicrobial Chemotherapy

102

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“…However, accurate susceptibility testing for these compounds, which is known to be essential for therapeutic management, is still problematic in routine clinical microbiology laboratories. It has been reported that polymyxin MICs may not be reproducible and that many factors influence its determination, such as the inoculum and the cation concentration content of the Mueller-Hinton medium (2,14,22,24). In addition, it has been observed that MICs obtained by agar dilution and Etest methods are higher than those obtained by the reference broth microdilution technique (17).…”

Section: Discussionmentioning

confidence: 81%

Cation Concentration Variability of Four Distinct Mueller-Hinton Agar Brands Influences Polymyxin B Susceptibility Results

et al. 2012

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bPolymyxins have been the only alternative therapeutic option for the treatment of serious infections caused by multidrug-resistant Acinetobacter baumannii or Pseudomonas aeruginosa isolates. For this reason, it is of crucial importance that susceptibility tests provide accurate results when testing these drug-pathogen combinations. In this study, the effect of cation concentration variability found on different commercial brands of Mueller-Hinton agar (MHA) for testing polymyxin B susceptibility was evaluated. The polymyxin B susceptibilities determined using Etest and disk diffusion were compared to those determined by the CLSI reference broth microdilution method. In general, the polymyxin B MIC values were higher when determined by Etest than when determined by broth microdilution against both A. baumannii and P. aeruginosa isolates. A high very major error rate (10%) was observed, as well as a trend toward lower MICs, compared to those determined by broth microdilution when the Merck MHA was tested by Etest. Poor essential agreement rates (10 to 70%) were observed for P. aeruginosa when all MHA brands were tested by Etest. Although an excellent categorical agreement rate (100%) was seen between the disk diffusion and broth microdilution methods for P. aeruginosa, larger zones of inhibition were shown obtained using the Merck MHA. The high cation concentration variability found for the MHA brands tested correlated to the low accuracy, and discrepancies in the polymyxin B MICs were determined by Etest method, particularly for P. aeruginosa isolates.

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“…However, both of ours and Kim’s studies revealed that carbapenemase-producing K. pneumoniae isolates exhibited a higher rate of ATM-AVI inoculum effect than E. coli . In the literature, variations in PBP3 enzymes and carbapenemase activity, or the production of other β-lactamases among different species of Enterobacteriaceae might all affect the magnitude of inoculum effect ( 14 , 34 , 35 ). The presence of inoculum effects suggested potential benefits of higher doses or combination therapy to combat CPE infections with high bacterial burden.…”

Section: Discussionmentioning

confidence: 99%