Disease relevance of Penicillin Resistance

• A proteomic analysis of penicillin resistance in Streptococcus pneumoniae reveals a novel role for PstS, a subunit of the phosphate ABC transporter [1].
• Contribution of a TEM-1-like beta-lactamase to penicillin resistance in Neisseria gonorrhoeae [2].
• Association of a penicillin resistance gene with a tetracycline resistance plasmid (PTP-2) in Staphylococcus aureus [3].
• Otitis media therapy is influenced by penicillin-resistance and current recommendations are that amoxicillin is the drug of choice for this infection, given at a double dose of 80 to 90 mg/kg/day [4].
• Of 178 isolates from cases of neonatal GBS sepsis collected from 1995 to 1998, 8 and 4.5% were resistant to erythromycin and clindamycin, respectively, and one isolate showed intermediate penicillin resistance (MIC, 0.25 microg/ml) [5].

High impact information on Penicillin Resistance

• Pneumococci can be screened for penicillin resistance with a modified Kirby--Bauer technic; the strains with zones of less than 35 mm around 6-microgram penicillin disks or less than 25 mm around 5-microgram methicillin disks should be tested for sensitivity to penicillin by measurements of minimum inhibitory concentration [6].
• Tolerance is thus a common, clinically important form of penicillin resistance, that differs from previously described forms of pencillin resistance, that due to beta-lactamase, and that due to "intrinsic" (e.g., methicillin resistance) mechanisms [7].
• Several different alleles of murM cloned in plasmid pLS578 and introduced into a murM deletion mutant of the penicillin-resistant strain Pen6 were able to reconstitute each one of the three mutant phenotypes: the highly branched cell wall structure, original high level of penicillin resistance, and normal sensitivity to lysis [8].
• Plasmid-mediated gentamicin resistance in up to 50% of enterococcal isolates, along with enhanced penicillin resistance in some strains, leaves few therapeutic options [9].
• Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk [10].

Chemical compound and disease context of Penicillin Resistance

• Although penicillin resistance among Streptococcus pneumoniae strains is increasing in many areas, resistance to clindamycin remains low [11].
• All cases of anogenital gonorrhea caused by beta-lactamase producing Neisseria gonorrheae (11 patients), gonococci with high-level, plasmid-mediated tetracycline resistance (11 patients), or gonococci with chromosomally mediated penicillin resistance (22 patients) were cured [12].
• Determination of penicillin resistance in Streptococcus pneumoniae and use of co-trimoxazole in treatment of pneumococcal pneumoniae [13].
• Metronidazole susceptibility (generally) and penicillin resistance among Bacteroides species were consistent findings, and most isolates were susceptible to imipenem, but other results varied between and within species [14].
• A total of 152 strains of Streptococcus pneumoniae from diverse geographic areas in the United States and with different levels of penicillin resistance were tested against five broad-spectrum cephalosporins, ampicillin, piperacillin, ticarcillin, and three beta-lactamase inhibitor combinations [15].

Biological context of Penicillin Resistance

• Examination of strain 277 showed two plasmids, a 37S species encoding for penicillin resistance (Penr) and a 21S species containing the gene(s) responsible for tetracycline resistance (Tetr) [16].
• These results suggest that amino acid substitution of Thr-371 contributes to the development of penicillin resistance in PRSP strains with altered pbp2x and pbp2b genes [17].
• The results suggest that, for both R plasmids, penicillin resistance is entirely attributable to the presence of beta-lactamase activity [18].
• Penicillin-resistant pneumococci carry sequences of heterologous origin in their pbp genes and also in the recently identified murM: a gene essential for expression of penicillin resistance and for the unique cell wall structure of penicillin-resistant pneumococci [19].
• The integration of foreign DNA sequences in the pneumococcal PBP genes leads to the remodeling of at least four of the five PBPs that change in their kinetic properties and increase in the penicillin resistance level of the bacteria also seems to involve increased production of the low-affinity binding proteins [20].

Anatomical context of Penicillin Resistance

• Mechanism of intrinsic penicillin-resistance in Staphylococcus aureus. Binding of penicillin G to the cytoplasmic membrane of resistant staphylococci [21].

Associations of Penicillin Resistance with chemical compounds

• Penicillin resistance is now widespread and the frequency of isolates that are resistant to erythromycin has risen [22].
• The resistance percentages among the cephalosporins, macrolides, chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole were consistently higher among penicillin-intermediate strains than among susceptible isolates and even higher still among organisms expressing high-level penicillin resistance [23].
• In contrast, this combination was active in vivo against strain SF-195, which exhibited intermediate-level penicillin resistance (MIC, 32 micrograms/ml), likely reflecting the ability of high-dose ampicillin to achieve enough binding to low-affinity penicillin-binding proteins to cause augmented aminoglycoside uptake [24].
• Regardless of the classification of penicillin resistance, all isolates were classified as susceptible to cefotaxime, cefpirome, cefpodoxime, clarithromycin, imipenem, rifampin, and vancomycin on the basis of National Committee for Clinical Laboratory Standards interpretive guidelines [25].
• These results suggest that, unlike that of penicillin resistance, the spread of S. pneumoniae ciprofloxacin resistance in Canada is currently not attributable to clonal dissemination [26].

Gene context of Penicillin Resistance

• To further link the expression of the ABC phosphate transporter with penicillin resistance, we looked at pstS mRNA levels in 12 independent clinical isolates sensitive and resistant to penicillin and found an excellent correlation between resistance and increased expression of pstS [1].
• Rapid chemiluminescent nucleic acid assays for detection of TEM-1 beta-lactamase-mediated penicillin resistance in Neisseria gonorrhoeae and other bacteria [27].
• The loss of beta-lactamase activity was associated with a reduction in the level of penicillin resistance conferred by the mutants upon their host strain [18].
• The problems due to possible spread of MRSA to the community, emergence of penicillin resistance in S. pneumoniae, ampicillin resistance in H. influenzae, and multiresistance among common enteric pathogens are highlighted [28].
• Transformation experiments with pbp1b and 2a genes isolated from two resistant strains (MICs, 4 and 16 microg/mL) failed to transform pneumococcal strains to increased levels of penicillin resistance [29].

Analytical, diagnostic and therapeutic context of Penicillin Resistance

• Site-directed mutagenesis was then used to determine whether particular amino acid substitutions at specific positions in PBP 1A mediate penicillin resistance [30].
• Sequence analysis results of the pbp2b and pbpX alleles from these strains were in keeping with acquired penicillin resistance [31].
• Seventy-five Staph. aureus isolates were genotyped by pulsed-field gel electrophoresis, tested for enterotoxin (SE) production by reversed passive latex agglutination, for SE genes by multiplex polymerase chain reaction, and for penicillin resistance by the cloverleaf method [32].

References