F Plasmids Are the Major Carriers of Antibiotic Resistance Genes in Human-Associated Commensal Escherichia coli

ABSTRACT The evolution and propagation of antibiotic resistance by bacterial pathogens are significant threats to global public health. Contemporary DNA sequencing tools were applied here to gain insight into carriage of antibiotic resistance genes in Escherichia coli, a ubiquitous commensal bacterium in the gut microbiome in humans and many animals, and a common pathogen. Draft genome sequences generated for a collection of 101 E. coli strains isolated from healthy undergraduate students showed that horizontally acquired antibiotic resistance genes accounted for most resistance phenotypes, the primary exception being resistance to quinolones due to chromosomal mutations. A subset of 29 diverse isolates carrying acquired resistance genes and 21 control isolates lacking such genes were further subjected to long-read DNA sequencing to enable complete or nearly complete genome assembly. Acquired resistance genes primarily resided on F plasmids (101/153 [67%]), with smaller numbers on chromosomes (30/153 [20%]), IncI complex plasmids (15/153 [10%]), and small mobilizable plasmids (5/153 [3%]). Nearly all resistance genes were found in the context of known transposable elements. Very few structurally conserved plasmids with antibiotic resistance genes were identified, with the exception of an ∼90-kb F plasmid in sequence type 1193 (ST1193) isolates that appears to serve as a platform for resistance genes and may have virulence-related functions as well. Carriage of antibiotic resistance genes on transposable elements and mobile plasmids in commensal E. coli renders the resistome highly dynamic. IMPORTANCE Rising antibiotic resistance in human-associated bacterial pathogens is a serious threat to our ability to treat many infectious diseases. It is critical to understand how acquired resistance genes move in and through bacteria associated with humans, particularly for species such as Escherichia coli that are very common in the human gut but can also be dangerous pathogens. This work combined two distinct DNA sequencing approaches to allow us to explore the genomes of E. coli from college students to show that the antibiotic resistance genes these bacteria have acquired are usually carried on a specific type of plasmid that is naturally transferrable to other E. coli, and likely to other related bacteria.

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bla OXA-48-like genome architecture among carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in the Netherlands

Microbial Genomics ◽

10.1099/mgen.0.000512 ◽

2021 ◽

Vol 7 (5) ◽

Author(s):

Antoni P. A. Hendrickx ◽

Fabian Landman ◽

Angela de Haan ◽

Sandra Witteveen ◽

Marga G. van Santen-Verheuvel ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

The Netherlands ◽

Resistance Genes ◽

Type Species ◽

Antibiotic Resistance Genes ◽

Gene Content ◽

Content Type ◽

E Coli ◽

Link Type

Carbapenem-hydrolysing enzymes belonging to the OXA-48-like group are encoded by bla OXA-48-like alleles and are abundant among Enterobacterales in the Netherlands. Therefore, the objective here was to investigate the characteristics, gene content and diversity of the bla OXA-48-like carrying plasmids and chromosomes of Escherichia coli and Klebsiella pneumoniae collected in the Dutch national surveillance from 2014 to 2019 in comparison with genome sequences from 29 countries. A combination of short-read genome sequencing with long-read sequencing enabled the reconstruction of 47 and 132 complete bla OXA-48-like plasmids for E. coli and K. pneumoniae , respectively. Seven distinct plasmid groups designated as pOXA-48-1 to pOXA-48-5, pOXA-181 and pOXA-232 were identified in the Netherlands which were similar to internationally reported plasmids obtained from countries from North and South America, Europe, Asia and Oceania. The seven plasmid groups varied in size, G+C content, presence of antibiotic resistance genes, replicon family and gene content. The pOXA-48-1 to pOXA-48-5 plasmids were variable, and the pOXA-181 and pOXA-232 plasmids were conserved. The pOXA-48-1, pOXA-48-2, pOXA-48-3 and pOXA-48-5 groups contained a putative conjugation system, but this was absent in the pOXA-48-4, pOXA-181 and pOXA-232 plasmid groups. pOXA-48 plasmids contained the PemI antitoxin, while the pOXA-181 and pOXA-232 plasmids did not. Furthermore, the pOXA-181 plasmids carried a virB2-virB3-virB9-virB10-virB11 type IV secretion system, while the pOXA-48 plasmids and pOXA-232 lacked this system. A group of non-related pOXA-48 plasmids from the Netherlands contained different resistance genes, non-IncL-type replicons or no replicons. Whole genome multilocus sequence typing revealed that the bla OXA-48-like plasmids were found in a wide variety of genetic backgrounds in contrast to chromosomally encoded bla OXA-48-like alleles. Chromosomally localized bla OXA-48 and bla OXA-244 alleles were located on genetic elements of variable sizes and comprised regions of pOXA-48 plasmids. The bla OXA-48-like genetic element was flanked by a direct repeat upstream of IS1R, and was found at multiple locations in the chromosomes of E. coli . Lastly, K. pneumoniae isolates carrying bla OXA-48 or bla OXA-232 were mostly resistant for meropenem, whereas E. coli bla OXA-48, bla OXA-181 and chromosomal bla OXA-48 or bla OXA-244 isolates were mostly sensitive. In conclusion, the overall bla OXA-48-like plasmid population in the Netherlands is conserved and similar to that reported for other countries, confirming global dissemination of bla OXA-48-like plasmids. Variations in size, presence of antibiotic resistance genes and gene content impacted pOXA-48, pOXA-181 and pOXA-232 plasmid architecture.

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Phylum barrier and Escherichia coli intra-species phylogeny drive the acquisition of antibiotic-resistance genes

Microbial Genomics ◽

10.1099/mgen.0.000489 ◽

2021 ◽

Vol 7 (8) ◽

Author(s):

Marie Petitjean ◽

Bénédicte Condamine ◽

Charles Burdet ◽

Erick Denamur ◽

Etienne Ruppé

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Resistance Genes ◽

Type Species ◽

Antibiotic Resistance Genes ◽

Resistance Pattern ◽

Content Type ◽

E Coli ◽

Link Type ◽

Specific Distribution

Escherichia coli is a ubiquitous bacterium that has been widely exposed to antibiotics over the last 70 years. It has adapted by acquiring different antibiotic-resistance genes (ARGs), the census of which we aim to characterize here. To do so, we analysed 70 301 E. coli genomes obtained from the EnteroBase database and detected 1 027 651 ARGs using the AMRFinder, Mustard and ResfinderFG ARG databases. We observed a strong phylogroup and clonal lineage specific distribution of some ARGs, supporting the argument for epistasis between ARGs and the strain genetic background. However, each phylogroup had ARGs conferring a similar antibiotic class resistance pattern, indicating phenotypic adaptive convergence. The G+C content or the type of ARG was not associated with the frequency of the ARG in the database. In addition, we identified ARGs from anaerobic, non- Proteobacteria bacteria in four genomes of E. coli , supporting the hypothesis that the transfer between anaerobic bacteria and E. coli can spontaneously occur but remains exceptional. In conclusion, we showed that phylum barrier and intra-species phylogenetic history are major drivers of the acquisition of a resistome in E. coli .

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Discovery ofmcr-1-Mediated Colistin Resistance in a Highly VirulentEscherichia coliLineage

mSphere ◽

10.1128/msphere.00486-18 ◽

2018 ◽

Vol 3 (5) ◽

Cited By ~ 12

Author(s):

Brian M. Forde ◽

Hosam M. Zowawi ◽

Patrick N. A. Harris ◽

Leah Roberts ◽

Emad Ibrahim ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Neonatal Meningitis ◽

Colistin Resistance ◽

Content Type ◽

E Coli ◽

Virulence Potential ◽

High Virulence

ABSTRACTResistance to last-line polymyxins mediated by the plasmid-borne mobile colistin resistance gene (mcr-1) represents a new threat to global human health. Here we present the complete genome sequence of anmcr-1-positive multidrug-resistantEscherichia colistrain (MS8345). We show that MS8345 belongs to serotype O2:K1:H4, has a large 241,164-bp IncHI2 plasmid that carries 15 other antibiotic resistance genes (including the extended-spectrum β-lactamaseblaCTX-M-1) and 3 putative multidrug efflux systems, and contains 14 chromosomally encoded antibiotic resistance genes. MS8345 also carries a large ColV-like virulence plasmid that has been associated withE. colibacteremia. Whole-genome phylogeny revealed that MS8345 clusters within a discrete clade in the sequence type 95 (ST95) lineage, and MS8345 is very closely related to the highly virulent O45:K1:H4 clone associated with neonatal meningitis. Overall, the acquisition of a plasmid carrying resistance to colistin and multiple other antibiotics in this virulentE. colilineage is concerning and might herald an era where the empirical treatment of ST95 infections becomes increasingly more difficult.IMPORTANCEEscherichia coliST95 is a globally disseminated clone frequently associated with bloodstream infections and neonatal meningitis. However, the ST95 lineage is defined by low levels of drug resistance amongst clinical isolates, which normally provides for uncomplicated treatment options. Here, we provide the first detailed genomic analysis of anE. coliST95 isolate that has both high virulence potential and resistance to multiple antibiotics. Using the genome, we predicted its virulence and antibiotic resistance mechanisms, which include resistance to last-line antibiotics mediated by the plasmid-bornemcr-1gene. Finding an ST95 isolate resistant to nearly all antibiotics that also has a high virulence potential is of major clinical importance and underscores the need to monitor new and emerging trends in antibiotic resistance development in this important global lineage.

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Resistance Gene Carriage Predicts Growth of Natural and ClinicalEscherichia coliIsolates in the Absence of Antibiotics

Applied and Environmental Microbiology ◽

10.1128/aem.02111-18 ◽

2018 ◽

Vol 85 (4) ◽

Cited By ~ 4

Author(s):

Richard C. Allen ◽

Daniel C. Angst ◽

Alex R. Hall

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Genetic Variation ◽

Resistance Gene ◽

Resistance Genes ◽

Bacterial Pathogens ◽

Antibiotic Resistance Genes ◽

Resistant Bacteria ◽

Content Type ◽

Free Growth

ABSTRACTBacterial pathogens that carry antibiotic resistance alleles sometimes pay a cost in the form of impaired growth in antibiotic-free conditions. This cost of resistance is expected to be a key parameter for understanding how resistance spreads and persists in pathogen populations. Analysis of individual resistance alleles from laboratory evolution and natural isolates has shown they are typically costly, but these costs are highly variable and influenced by genetic variation at other loci. It therefore remains unclear how strongly resistance is linked to impaired antibiotic-free growth in bacteria from natural and clinical scenarios, where resistance alleles are likely to coincide with other types of genetic variation. To investigate this, we measured the growth of 92 natural and clinicalEscherichia coliisolates across three antibiotic-free environments. We then tested whether variation of antibiotic-free growth among isolates was predicted by their resistance to 10 antibiotics, while accounting for the phylogenetic structure of the data. We found that isolates with similar resistance profiles had similar antibiotic-free growth profiles, but it was not simply that higher average resistance was associated with impaired growth. Next, we used whole-genome sequences to identify antibiotic resistance genes and found that isolates carrying a greater number of resistance gene types grew relatively poorly in antibiotic-free conditions, even when the resistance genes they carried were different. This suggests that the resistance of bacterial pathogens is linked to growth costs in nature, but it is the total genetic burden and multivariate resistance phenotype that predict these costs, rather than individual alleles or mean resistance across antibiotics.IMPORTANCEManaging the spread of antibiotic resistance in bacterial pathogens is a major challenge for global public health. Central to this challenge is understanding whether resistance is linked to impaired bacterial growth in the absence of antibiotics, because this determines whether resistance declines when bacteria are no longer exposed to antibiotics. We studied 92 isolates of the key bacterial pathogenEscherichia coli; these isolates varied in both their antibiotic resistance genes and other parts of the genome. Taking this approach, rather than focusing on individual genetic changes associated with resistance as in much previous work, revealed that growth without antibiotics was linked to the number of specialized resistance genes carried and the combination of antibiotics to which isolates were resistant but was not linked to average antibiotic resistance. This approach provides new insights into the genetic factors driving the long-term persistence of antibiotic-resistant bacteria, which is important for future efforts to predict and manage resistance.

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Draft Genome Sequences of Cefepime-Resistant and -Susceptible Escherichia coli Strains and Imipenem-Resistant and -Susceptible Pseudomonas aeruginosa Strains

Microbiology Resource Announcements ◽

10.1128/mra.00749-21 ◽

2021 ◽

Vol 10 (48) ◽

Author(s):

Kendra Batchelder ◽

Liz Ward ◽

Elsa Collins ◽

Caitlin Miles ◽

Stefania Palm ◽

...

Keyword(s):

Escherichia Coli ◽

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Resistance Genes ◽

Draft Genome ◽

Antibiotic Resistance Genes ◽

Genome Sequences ◽

Content Type ◽

E Coli

Draft genome sequences of Escherichia coli and Pseudomonas aeruginosa strains collected from clinical infections were used to determine the prevalence of newly emerging antibiotic resistance genes in Maine. Comparisons between cefepime-resistant and -susceptible E. coli strains and imipenem-resistant and -susceptible P. aeruginosa strains are being conducted.

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Comparative Genome Analysis of an Extensively Drug-Resistant Isolate of Avian Sequence Type 167 Escherichia coli Strain Sanji with Novel In Silico Serotype O89b:H9

mSystems ◽

10.1128/msystems.00242-18 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 5

Author(s):

Xiancheng Zeng ◽

Xuelin Chi ◽

Brian T. Ho ◽

Damee Moon ◽

Christine Lambert ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Resistance Genes ◽

In Silico ◽

Antibiotic Resistance Genes ◽

Secretion System ◽

Sequence Type ◽

Content Type ◽

E Coli ◽

Multiple Paths

ABSTRACT Extensive drug resistance (XDR) is an escalating global problem. Escherichia coli strain Sanji was isolated from an outbreak of pheasant colibacillosis in Fujian province, China, in 2011. This strain has XDR properties, exhibiting sensitivity to carbapenems but no other classes of known antibiotics. Whole-genome sequencing revealed a total of 32 known antibiotic resistance genes, many associated with insertion sequence 26 (IS26) elements. These were found on the Sanji chromosome and 2 of its 6 plasmids, pSJ_255 and pSJ_82. The Sanji chromosome also harbors a type 2 secretion system (T2SS), a type 3 secretion system (T3SS), a type 6 secretion system (T6SS), and several putative prophages. Sanji and other ST167 strains have a previously uncharacterized O-antigen (O89b) that is most closely related to serotype O89 as determined on the basis of analysis of the wzm-wzt genes and in silico serotyping. This O89b-antigen gene cluster was also found in the genomes of a few other pathogenic sequence type 617 (ST617) and ST10 complex strains. A time-scaled phylogeny inferred from comparative single nucleotide variant analysis indicated that development of these O89b-containing lineages emerged about 30 years ago. Comparative sequence analysis revealed that the core genome of Sanji is nearly identical to that of several recently sequenced strains of pathogenic XDR E. coli belonging to the ST167 group. Comparison of the mobile elements among the different ST167 genomes revealed that each genome carries a distinct set of multidrug resistance genes on different types of plasmids, indicating that there are multiple paths toward the emergence of XDR in E. coli. IMPORTANCE E. coli strain Sanji is the first sequenced and analyzed genome of the recently emerged pathogenic XDR strains with sequence type ST167 and novel in silico serotype O89b:H9. Comparison of the genomes of Sanji with other ST167 strains revealed distinct sets of different plasmids, mobile IS elements, and antibiotic resistance genes in each genome, indicating that there exist multiple paths toward achieving XDR. The emergence of these pathogenic ST167 E. coli strains with diverse XDR capabilities highlights the difficulty of preventing or mitigating the development of XDR properties in bacteria and points to the importance of better understanding of the shared underlying virulence mechanisms and physiology of pathogenic bacteria.

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Limited and Strain-Specific Transcriptional and Growth Responses to Acquisition of a Multidrug Resistance Plasmid in Genetically Diverse Escherichia coli Lineages

mSystems ◽

10.1128/msystems.00083-21 ◽

2021 ◽

Vol 6 (2) ◽

Author(s):

Steven Dunn ◽

Laura Carrilero ◽

Michael Brockhurst ◽

Alan McNally

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Multidrug Resistance ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Growth Responses ◽

Fitness Costs ◽

Transcriptional Responses ◽

Content Type ◽

E Coli

ABSTRACT Multidrug-resistant (MDR) Escherichia coli strains are a major global threat to human health, wherein multidrug resistance is primarily spread by MDR plasmid acquisition. MDR plasmids are not widely distributed across the entire E. coli species, but instead are concentrated in a small number of clones. Here, we test if diverse E. coli strains vary in their ability to acquire and maintain MDR plasmids and if this relates to their transcriptional response following plasmid acquisition. We used strains from across the diversity of E. coli strains, including the common MDR lineage sequence type 131 (ST131) and the IncF plasmid pLL35, carrying multiple antibiotic resistance genes. Strains varied in their ability to acquire pLL35 by conjugation, but all were able to stably maintain the plasmid. The effects of pLL35 acquisition on cefotaxime resistance and growth also varied among strains, with growth responses ranging from a small decrease to a small increase in growth of the plasmid carrier relative to the parental strain. Transcriptional responses to pLL35 acquisition were limited in scale and highly strain specific. We observed transcriptional responses at the operon or regulon level—possibly due to stress responses or interactions with resident mobile genetic elements (MGEs). Subtle transcriptional responses consistent across all strains were observed affecting functions, such as anaerobic metabolism, previously shown to be under negative frequency-dependent selection in MDR E. coli. Overall, there was no correlation between the magnitudes of the transcriptional and growth responses across strains. Together, these data suggest that fitness costs arising from transcriptional disruption are unlikely to act as a barrier to dissemination of this MDR plasmid in E. coli. IMPORTANCE Plasmids play a key role in bacterial evolution by transferring adaptive functions between lineages that often enable invasion of new niches, including driving the spread of antibiotic resistance genes. Fitness costs of plasmid acquisition arising from the disruption of cellular processes could limit the spread of multidrug resistance plasmids. However, the impacts of plasmid acquisition are typically measured in lab-adapted strains rather than natural isolates, which act as reservoirs for the maintenance and transmission of plasmids to clinically relevant strains. Using a clinical multidrug resistance plasmid and a diverse collection of E. coli strains isolated from clinical infections and natural environments, we show that plasmid acquisition had only limited and highly strain-specific effects on bacterial growth and transcription under laboratory conditions. These findings suggest that fitness costs arising from transcriptional disruption are unlikely to act as a barrier to transmission of this plasmid in natural populations of E. coli.

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Mechanisms of Resistance in Multiple-Antibiotic-Resistant Escherichia coli Strains of Human, Animal, and Food Origins

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.10.3996-4001.2004 ◽

2004 ◽

Vol 48 (10) ◽

pp. 3996-4001 ◽

Cited By ~ 269

Author(s):

Yolanda Sáenz ◽

Laura Briñas ◽

Elena Domínguez ◽

Joaquim Ruiz ◽

Myriam Zarazaga ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Amino Acid ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Mechanisms Of Resistance ◽

Antibiotic Resistant ◽

E Coli ◽

Class 1 ◽

Human Animal

ABSTRACT Seventeen multiple-antibiotic-resistant nonpathogenic Escherichia coli strains of human, animal, and food origins showed a wide variety of antibiotic resistance genes, many of them carried by class 1 and class 2 integrons. Amino acid changes in MarR and mutations in marO were identified for 15 and 14 E. coli strains, respectively.

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Antibiotic-resistant Escherichia coli and Salmonella spp. associated with dairy cattle and farm environment having public health significance

Veterinary World ◽

10.14202/vetworld.2019.984-993 ◽

2019 ◽

Vol 12 (7) ◽

pp. 984-993 ◽

Cited By ~ 14

Author(s):

Md. Abdus Sobur ◽

Abdullah Al Momen Sabuj ◽

Ripon Sarker ◽

A. M. M. Taufiqur Rahman ◽

S. M. Lutful Kabir ◽

...

Keyword(s):

Public Health ◽

Escherichia Coli ◽

Antibiotic Resistance ◽

Resistance Genes ◽

One Health ◽

Dairy Farm ◽

Antibiotic Resistance Genes ◽

Salmonella Spp ◽

Antibiotic Resistant ◽

E Coli

Aim: The present study was carried out to determine load of total bacteria, Escherichia coli and Salmonella spp. in dairy farm and its environmental components. In addition, the antibiogram profile of the isolated bacteria having public health impact was also determined along with identification of virulence and resistance genes by polymerase chain reaction (PCR) under a one-health approach. Materials and Methods: A total of 240 samples of six types (cow dung - 15, milk - 10, milkers' hand wash - 10, soil - 10 water - 5, and vegetables - 10) were collected from four dairy farms. For enumeration, the samples were cultured onto plate count agar, eosin methylene blue, and xylose-lysine deoxycholate agar and the isolation and identification of the E. coli and Salmonella spp. were performed based on morphology, cultural, staining, and biochemical properties followed by PCR. The pathogenic strains of E. coli stx1, stx2, and rfbO157 were also identified through PCR. The isolates were subjected to antimicrobial susceptibility test against 12 commonly used antibiotics by disk diffusion method. Detection of antibiotic resistance genes ereA, tetA, tetB, and SHV were performed by PCR. Results: The mean total bacterial count, E. coli and Salmonella spp. count in the samples ranged from 4.54±0.05 to 8.65±0.06, 3.62±0.07 to 7.04±0.48, and 2.52±0.08 to 5.87±0.05 log colony-forming unit/g or ml, respectively. Out of 240 samples, 180 (75%) isolates of E. coli and 136 (56.67%) isolates of Salmonella spp. were recovered through cultural and molecular tests. Among the 180 E. coli isolates, 47 (26.11%) were found positive for the presence of all the three virulent genes, of which stx1 was the most prevalent (13.33%). Only three isolates were identified as enterohemorrhagic E. coli. Antibiotic sensitivity test revealed that both E. coli and Salmonella spp. were found highly resistant to azithromycin, tetracycline, erythromycin, oxytetracycline, and ertapenem and susceptible to gentamycin, ciprofloxacin, and imipenem. Among the four antibiotic resistance genes, the most observable was tetA (80.51-84.74%) in E. coli and Salmonella spp. and SHV genes were the lowest one (22.06-25%). Conclusion: Dairy farm and their environmental components carry antibiotic-resistant pathogenic E. coli and Salmonella spp. that are potential threat for human health which requires a one-health approach to combat the threat.

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Predicting Antibiotic Resistance in Gram-Negative Bacilli from Resistance Genes

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02462-18 ◽

2019 ◽

Vol 63 (4) ◽

Cited By ~ 3

Author(s):

G. Terrance Walker ◽

Julia Quan ◽

Stephen G. Higgins ◽

Nikhil Toraskar ◽

Weizhong Chang ◽

...

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Unknown Origin ◽

Bacterial Isolates ◽

Antibiotic Resistant ◽

Predictive Values ◽

Content Type ◽

Phenotypic Resistance ◽

E Coli

ABSTRACT We developed a rapid high-throughput PCR test and evaluated highly antibiotic-resistant clinical isolates of Escherichia coli (n = 2,919), Klebsiella pneumoniae (n = 1,974), Proteus mirabilis (n = 1,150), and Pseudomonas aeruginosa (n = 1,484) for several antibiotic resistance genes for comparison with phenotypic resistance across penicillins, cephalosporins, carbapenems, aminoglycosides, trimethoprim-sulfamethoxazole, fluoroquinolones, and macrolides. The isolates originated from hospitals in North America (34%), Europe (23%), Asia (13%), South America (12%), Africa (7%), or Oceania (1%) or were of unknown origin (9%). We developed statistical methods to predict phenotypic resistance from resistance genes for 49 antibiotic-organism combinations, including gentamicin, tobramycin, ciprofloxacin, levofloxacin, trimethoprim-sulfamethoxazole, ertapenem, imipenem, cefazolin, cefepime, cefotaxime, ceftazidime, ceftriaxone, ampicillin, and aztreonam. Average positive predictive values for genotypic prediction of phenotypic resistance were 91% for E. coli, 93% for K. pneumoniae, 87% for P. mirabilis, and 92% for P. aeruginosa across the various antibiotics for this highly resistant cohort of bacterial isolates.

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