Alterations of the penicillin-binding proteins and murM alleles of clinical Streptococcus pneumoniae isolates with high-level resistance to amoxicillin in Spain

Cafini, Fabio; Campo, Rosa del; Alou, Luís; Sevillano, David; Morosini, María Isabel; Baquero, Fernando; Prieto, J.

doi:10.1093/jac/dki442

Cited by 39 publications

(46 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, the region of PBP 2B from amino acids 557 to 647 appeared to be relevant for resistance, especially among strains with high amoxicillin MICs, which confirms previous findings (5,12,29).…”

Section: Yr Of Isolationsupporting

confidence: 91%

“…Alterations in the conserved motifs in PBP 2B are associated with penicillin G resistance, and alterations in PBP 2X mediate low-level resistance to cephalosporins (1,8,11,18). The region of PBP 2B from amino acids 538 to 642 also appears to be relevant for resistance, especially among strains with high amoxicillin MICs (5,29). Additional alterations in PBP 1A raise the penicillin G and cefotaxime MICs (1,35,42,47).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Comparative Antipneumococcal Activities of Sulopenem and Other Drugs

Kosowska-Shick

Ednie

McGhee

et al. 2009

Antimicrob Agents Chemother

View full text Add to dashboard Cite

For 297 penicillin-susceptible, -intermediate, and -resistant pneumococcal strains, the sulopenem MIC 50 s were 0.008, 0.06, and 0.25, respectively, and the sulopenem MIC 90 s were 0.016, 0.25, and 0.5 g/ml, respectively. The MIC 50 s of amoxicillin for the corresponding strains were 0.03, 0.25, and 2.0 g/ml, respectively, and the MIC 90 s were 0.03, 1.0, and 8.0 g/ml, respectively. The combination of amoxicillin and clavulanate gave MICs similar to those obtained with amoxicillin alone. The sulopenem MICs were similar to those of imipenem and meropenem. The MICs of ß-lactams increased with those of penicillin G, and among the quinolones tested, moxifloxacin had the lowest MICs. Additionally, 45 strains of drug-resistant type 19A pneumococci were tested by agar dilution and gave sulopenem MIC 50 s and MIC 90 s of 1.0 and 2.0 g/ml, respectively. Both sulopenem and amoxicillin (with and without clavulanate) were bactericidal against all 12 strains tested at 2؋ MIC after 24 h. Thirty-one strains from 10 countries with various penicillin, amoxicillin, and carbapenems MICs, including those with the highest sulopenem MICs, were selected for sequencing analysis of the pbp1a, pbp2x, and pbp2b regions encoding the transpeptidase active site and MurM. We did not find any correlations between specific penicillin-binding protein-MurM patterns and changes in the MICs.The incidence of pneumococci resistant to penicillin G and other ß-lactam and non-ß-lactam compounds has increased at an alarming rate worldwide, including the United States. The major foci of infections currently include South Africa, Spain, and Central and Eastern Europe (26,27). A 1997 survey showed that 50.4% of 1,476 clinically significant pneumococcal isolates in the United States were not susceptible to penicillin (26). Of all strains tested, approximately 33% were macrolide resistant, with the highest rate of macrolide resistance being seen among penicillin-resistant strains, for which the MICs were Ն2.0 g/ml (26). A later survey, conducted as part of the Alexander Project (27), reported that the worldwide prevalence of pneumococci isolated between 1998 and 2000 for which penicillin G MICs were Ն2 g/ml was 18.2%, with the overall macrolide resistance rate being 24.6%. It is also important to note the higher rates of isolation of penicillin-intermediate and -resistant pneumococci (approximately 30%) in middle ear fluids from patients with refractory otitis media than from other isolation sites (4). Quinolone-resistant pneumococci have also been described (6,22,31). The problem of drug-resistant pneumococci is compounded by the ability of resistant clones to spread from country to country and from continent to continent (32, 34). In a recent paper, Pichichero and Casey (40) reported on the emergence in the United States of an otopathogenic strain of pneumococcus type 19A which is not covered by the current pediatric conjugate vaccine and which is resistant to all currently FDA-approved antibiotics for the treatment of acute otitis media in children. Anothe...

show abstract

Section: Yr Of Isolationsupporting

confidence: 91%

mentioning

confidence: 99%

Comparative Antipneumococcal Activities of Sulopenem and Other Drugs

Kosowska-Shick

Ednie

McGhee

et al. 2009

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Changes in three of the six pbp genes, encoding the penicillin-binding proteins (PBPs), which are active in peptidoglycan synthesis, are the major resistance factors (56). However, other determinants, such as variants of the murM gene, play a role in resistance expression as well (7,12,19,20).Modern typing methods, mainly multilocus sequence typing (MLST) (1), greatly facilitate tracking the geographic spread of specific S. pneumoniae strains and following the dynamics of microbial populations over time. It was found that relatively few clones, the so-called multiresistant international clones defined by the Pneumococcal Epidemiology Network (PMEN) (34; www.sph.emory.edu/pmen), cause increases in pneumococcal resistance to ␤-lactams and other drugs (29,36,44,47,57).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Expansion and Evolution of the Streptococcus pneumoniae Spain ^9V -ST156 Clonal Complex in Poland

Sadowy

Kuch

Gniadkowski

et al. 2010

Antimicrob Agents Chemother

View full text Add to dashboard Cite

In this study, we analyzed 118 penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) isolates (MICs, >0.12 g/ml) recovered in Poland in 2003 to 2005 from patients with respiratory tract diseases and invasive infections. Seven different serotypes (14, 9V, 23F, 19F, 6B, 19A, and 6A, in order of descending frequency), seven alleles of the murM gene (murMA, murMB6, and the new murMB12 to -16 alleles), and 31 multilocus sequence types (STs) were observed. The vast majority of the PNSP isolates (90.7%) belonged to the international multiresistant clones, and among these, the Spain 9V -ST156 clonal complex was the most prevalent (56 isolates) and was significantly overrepresented in invasive infections. The clone has been evolving rapidly, as demonstrated by the observed number of STs, the diversity in multiple-locus variable-number-tandem-repeat analysis (MLVA) types, and the polymorphism of pbp and pspA genes (coding for penicillin-binding proteins and the pneumococcal surface protein A, respectively). The presence and structure of the rlrA islet (encoding the pneumococcal pilus) were very well conserved. The Spain 9V -ST156 clonal complex has been largely responsible for a decreasing susceptibility to penicillin among pneumococci in Poland in recent years, in spite of a relatively moderate antimicrobial use.Streptococcus pneumoniae (pneumococcus) is a leading cause of community-acquired respiratory tract infections (RTIs) and one of the major agents of invasive bacterial diseases such as sepsis and meningitis (4). Its diminishing susceptibility to antimicrobials, especially to ␤-lactams (3,13,43,44,46), is of the highest concern. In a clinical isolate, the loss of ␤-lactam susceptibility results from DNA acquisition from a penicillin-nonsusceptible S. pneumoniae (PNSP) strain (11, 23, 51) or a viridans group streptococcus (14). Changes in three of the six pbp genes, encoding the penicillin-binding proteins (PBPs), which are active in peptidoglycan synthesis, are the major resistance factors (56). However, other determinants, such as variants of the murM gene, play a role in resistance expression as well (7,12,19,20).Modern typing methods, mainly multilocus sequence typing (MLST) (1), greatly facilitate tracking the geographic spread of specific S. pneumoniae strains and following the dynamics of microbial populations over time. It was found that relatively few clones, the so-called multiresistant international clones defined by the Pneumococcal Epidemiology Network (PMEN) (34; www.sph.emory.edu/pmen), cause increases in pneumococcal resistance to ␤-lactams and other drugs (29,36,44,47,57). The "epidemiologic success" of a particular S. pneumoniae clone may also arise from factors augmenting its fitness. These would include virulence factors which improve the survival of pneumococci in the human host (24), such as the highly polymorphic pneumococcal surface protein A (PspA) (25), involved in the protection of pneumococci against the host immune system (53). Another factor, a pilus, was recently proposed to contri...

show abstract

“…The binding affinities of antibiotics for PBP1A, PBP2X and PBP2B is thought to be important for antibacterial activity against S. pneumoniae. 7 Although the relationship between the binding affinities of antibiotics for PBPs and their bactericidal activities has yet to be definitively proven, it is possible that the potent bactericidal activity of ME1036 against the S. pneumoniae strains, including the gPRSPs, is caused by its strong affinities for PBPs. 8 Drug-resistant S. pneumoniae strains are usually isolated from the sputum, pharynx, nasal cavity or otorrhea of patients, and from the otitis media and tissues affected by adenoiditis in children.…”

Section: Antimicrobial Activity and Affinities To Pbps Y Hirai Et Almentioning

confidence: 99%

Correlation of the antimicrobial activity of ME1036 with its binding affinities to the penicillin-binding proteins from Streptococcus pneumoniae strains

Hirai¹,

Takahata²,

Yamada³

et al. 2011

J Antibiot

View full text Add to dashboard Cite

We have correlated the binding affinities of ME1036, a carbapenem, to the penicillin-binding proteins (PBPs) from Streptococcus pneumoniae strains, with its bactericidal potency against those same strains. Certain mutations in the PBPs from S. pneumonaie strains decrease the binding affinities of b-lactams for PBPs, which gives rise to clinical resistance to those b-lactams. ME1036 has been shown to be strongly active against genotypic penicillin-intermediate S. pneumoniae (gPISP) strains and genotypic penicillin-resistant S. pneumoniae (gPRSP) strains that contain more than one mutation in their PBPs, owing to its strong affinity for those PBPs.

show abstract

Alterations of the penicillin-binding proteins and murM alleles of clinical Streptococcus pneumoniae isolates with high-level resistance to amoxicillin in Spain

Cited by 39 publications

References 19 publications

Comparative Antipneumococcal Activities of Sulopenem and Other Drugs

Comparative Antipneumococcal Activities of Sulopenem and Other Drugs

Expansion and Evolution of the Streptococcus pneumoniae Spain ^9V -ST156 Clonal Complex in Poland

Correlation of the antimicrobial activity of ME1036 with its binding affinities to the penicillin-binding proteins from Streptococcus pneumoniae strains

Contact Info

Product

Resources

About

Alterations of the penicillin-binding proteins and murM alleles of clinical Streptococcus pneumoniae isolates with high-level resistance to amoxicillin in Spain

Cited by 39 publications

References 19 publications

Comparative Antipneumococcal Activities of Sulopenem and Other Drugs

Comparative Antipneumococcal Activities of Sulopenem and Other Drugs

Expansion and Evolution of the Streptococcus pneumoniae Spain 9V -ST156 Clonal Complex in Poland

Correlation of the antimicrobial activity of ME1036 with its binding affinities to the penicillin-binding proteins from Streptococcus pneumoniae strains

Contact Info

Product

Resources

About

Expansion and Evolution of the Streptococcus pneumoniae Spain ^9V -ST156 Clonal Complex in Poland