Transferrable Resistance to Tobramycin in
            <i>Klebsiella pneumoniae</i>
            and
            <i>Enterobacter cloacae</i>
            Associated with Enzymatic Acetylation of Tobramycin

In vitro interactions of ciprofloxacin with imipenem and amikacin were evaluated by the killing-curve technique against 26 Pseudomonas aeruginosa strains resistant to amikacin and resistant or moderately susceptible to ciprofloxacin and imipenem. Imipenem enhanced killing by ciprofloxacin in tests with 11 strains, whereas amikacin enhanced killing in tests with only 4 strains.Among the newer quinolones, ciprofloxacin has been proved the most effective against members of the family Enterobacteriaceae, with major antipseudomonal properties (1,5,7,9,10,17). However, in certain clinical situations it may be necessary for ciprofloxacin to be administered in combination with other antimicrobial agents, with the aim of expanding its antimicrobial spectrum, preventing the emergence of resistant mutants during therapy, and obtaining synergistic results.The purpose of this study was to evaluate in vitro the interactions of ciprofloxacin with amikacin and imipenem against multiresistant strains of Pseudomonas aeruginosa. Twenty-six strains, derived from urine (15 strains), sputum (5 strains), pus (4 strains), and blood (2 strains) cultures, were studied. By the disk diffusion method (2), 100% were resistant to ticarcillin, gentamicin, and amikacin, 90 and 70% were resistant to piperacillin and ceftazidime, respectively, 45% were resistant to imipenem, and 70% were resistant to ciprofloxacin. Ciprofloxacin was kindly provided by Bayer AG, Leverkusen, Federal Republic of Germany; amikacin sulfate was provided by Bristol Myers, Syracuse, N.Y.; and imipenem was provided by Merck Sharp & Dohme, Rahway, N.J.MICs and MBCs were determined for ciprofloxacin, amikacin, and impenem by the broth macrodilution technique in volumes of 1 ml. Unsupplemented Mueller-Hinton broth (BBL Microbiology Systems, Cockeysville, Md.) was used, and the inoculum was derived from an overnight culture after adjustment to 5 x 105 CFU/ml. The MIC was defined as the lowest concentration that completely inhibited growth, and the MBC was defined as the lowest concentration which produced .99.9% killing of the inoculum. With susceptibility cutoff points of 2 ,ug/ml for ciprofloxacin and 8 ,g/ml for imipenem and amikacin, 9 strains were moderately susceptible to ciprofloxacin (MIC, 0.5 to 2 ,ug/ml), 12 strains were moderately susceptible to imipenem (MIC, 4 to 8 ,ug/ml), and none was moderately susceptible to amikacin. The ciprofloxacin, imipenem, and amikacin MICs and MBCs for 90% of strains tested were 16 and 128, 32 and 128, and 512 and >512 ,ug/ml, respectively.Interaction studies of ciprofloxacin with imipenem and amikacin were simultaneously performed by time-kill curves (12) with the following modification. The traditional combination of one-quarter the MIC was not applied, because results based on high MICs could not have clinical rele-* Corresponding author.vance. Instead, for strains that were multiresistant or moderately susceptible to ciprofloxacin, killing studies were performed in Mueller-Hinton broth containing concentrations representing the me...

“…Seventeen P. aeruginosa strains were examined by the method of Minshew et al (13) for the production of aminoglycQside-modifying enzymes. They were detected in 14 strains.…”

mentioning

confidence: 99%

Ciprofloxacin interactions with imipenem and amikacin against multiresistant Pseudomonas aeruginosa

Giamarellou¹,

Petrikkos²

1987

“…It appears that an enzyme with an identical substrate range is also found in certain strains of P. aeruginosa, notably P. aeruginosa GN315. In addition, AAC(6')'s with substrate ranges somewhat similar to the enzymes characterized from these strains were identified in K. pneumoniae 355 and E. coli 264 by Minshew et al (7). Recently, Le Goffic and co-workers described a 6'-N-acetylating enzyme from a Moraxella glueidii strain, different from AAC(6')-I, and named this enzyme AAC(6')-II (6).…”

Section: Discussionmentioning

confidence: 99%

Enzymatic Modification of Aminoglycoside Antibiotics: a New 6′- N -Acetylating Enzyme from a Pseudomonas aeruginosa Isolate

Haas¹,

Biddlecome²,

Davies

et al. 1976

“…Transfer of antibiotic resistance was performed as previously described (19). The growth medium was brain heart infusion broth (Difco).…”

Section: Methodsmentioning

confidence: 99%

Common Plasmid Specifying Tobramycin Resistance Found in Two Enteric Bacteria Isolated from Burn Patients

Elwell

Inamine

Minshew

1978

Self Cite

Tobramycin-resistant burn wound isolates of Klebsiella pneumoniae and Enterobacter cloacae, together with Escherichia coli K-12 transconjugants from these two strains, were examined for plasmid deoxyribonucleic acid (DNA). All the resistant strains contained a common, high-molecular-weight, covalently closed circular DNA plasmid that was absent in the tobramycin-susceptible E. coli recipient strain. The common plasmid residing inELctocae was designated pIE098, and that residing in _..neumatie was designated pIE099. Both plasmid species were found to have a molecular mass of approximately 60 x 106 daltons and a guanine-plus-cytosine content of 50 mol%. The DNA that was extracted from all of the tobramycin-resistant strains tested was able to hybridize to 86 to 100% with pIE098 and pIE099 [3H]DNA generated by EcoRI to produce fragments of a size similar to those generated by BamHI. This study illustrates the) usefulness of simple screening methods for antibiotic resistance plasmids in a( hospital epidemiological situation.Infections caused by gram-negative bacilli currently constitute the most frequent type of nosocomial infection, a fact that has profound implications for patients with major burns. A serious threat to the control of burn wound infections has been the emergence of bacteria harboring transmissible antibiotic resistance plasmids (R plasmids) that are selected for under the pressure of intense antibiotic therapy (13,15,23,25). Minshew et al. (19) have reported the isolation of tobramycin-resistant strains of Klebsiella pneumoniae and Escherichia coli from burn patients undergoing tobramycin therapy. Tobramycin resistance in the Klebsiella and Enterobacter isolates could be transferred to E. coli recipients and was associated with the enzymatic acetylation of tobramycin and other aminoglycosides. The acetylating activities of these strains were found to resemble kanamycin acetyltransferase or an aminoglycoside-6'-acetyltransferase (9).This study reports the isolation and partial characterization of a common, self-transmissible R plasmid specifying tobramycin resistance in the Klebsiella and Enterobacter strains. The presence of a similar plasmid in these two enterobacteria indicates the probability of R-plasmid t Present address: Wenlcome Research Laboratories, Research Triangle Park, NC 27709.tt Present address: