The development of vancomycin resistance in a patient with methicillin-resistant Staphylococcus aureus infection.
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Aged↗
Biomedical subjects
A Tomasz
Publications and source records attributed to A Tomasz.
Heterogeneously vancomycin-resistant Staphylococcus epidermidis strain causing recurrent peritonitis in a dialysis patient during vancomycin therapy.
Methicillin-resistant Staphylococcus epidermidis (MRSE) was recovered over a 2-month period from the dialysis fluid of a peritoneal dialysis (PD) patient who experienced recurrent episodes of peritonitis during therapeutic and prophylactic use of vancomycin. Characterization of five consecutive MRSE isolates by molecular and microbiological methods showed that they were representatives of a single strain, had reduced susceptibility to vancomycin, did not react with DNA probes specific for the enterococcal vanA or vanB gene, and showed characteristics reminiscent of the properties of a recently described vancomycin-resistant laboratory mutant of Staphylococcus aureus. Cultures of these MRSE isolates were heterogeneous: they contained-with a frequency of 10(-4) to 10(-5)-bacteria for which vancomycin MICs were high (25 to 50 microg/ml) which could easily be selected to "take over" the cultures by using vancomycin selection in the laboratory. In contrast, the five consecutive MRSE isolates recovered from the PD patient during virtually continuous vancomycin therapy showed no indication for a similar enrichment of more resistant subpopulations, suggesting the existence of an "occult" infection site in the patient (presumably at the catheter exit site) which was not accessible to the antibiotic.
Adult↗
Molecular characterization of penicillin-resistant Streptococcus pneumoniae isolates from Bulgaria.
As part of an ongoing surveillance program of antibiotic-resistant Streptococcus pneumoniae in Sofia, Bulgaria, 120 penicillin-resistant strains (PRSP) (most of them recovered from children hospitalized with pneumococcal disease) were analyzed by microbiological and molecular methods. Several unique features of this collection are of particular interest. (i) Most isolates (112 of 120) were also resistant to trimethoprim-sulfamethoxazole (SXT) (97 of 120 isolates, or 80%), and over 70% (86 of 120) of the isolates were resistant to at least three antibiotics in addition to penicillin. (ii) Close to 80% of all isolates were represented by large clusters of bacteria, each with a unique serotype, antibiotype, and chromosomal macrorestriction pattern (determined by pulsed-field gel electrophoresis), as well as unique restriction fragmentation length polymorphisms of the penicillin-binding protein genes pbp1a, pbp2x, and pbp2b. (iii) A large proportion (45 of 120, or 38%) of the strains belonged to two internationally spread epidemic clones of S. pneumoniae, the first expressing capsular type 23F and the second expressing serotype 9. (iv) A unique Bulgarian cluster composed of eight serotype 19F isolates was resistant to tetracycline, SXT, cefotaxime, and extremely high levels of penicillin and erythromycin. Nevertheless, this clone did not react with either the erm or the mef DNA probes, and thus the mechanism of macrolide resistance in this group of PRSP remains to be elucidated.
Adolescent↗
Recurrent peritonitis in a patient on dialysis and prophylactic vancomycin.
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Adult↗
Low-level teicoplanin resistance and heteroresistance to vancomycin.
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Anti-Bacterial Agents↗
Accelerated evolution: emergence of multidrug resistant gram-positive bacterial pathogens in the 1990's.
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Drug Resistance, Multiple↗
Capsular transformation of a multidrug-resistant Streptococcus pneumoniae in vivo.
Several multidrug-resistant (MDR) isolates of Streptococcus pneumoniae recovered from a variety of clinical sources and expressing serotypes 9N, 14, 19F, and 3 could not be distinguished from the capsular type 23 Spanish/USA epidemic clone in antibiotype, pulsed-field gel electrophoretic pattern, and restriction fragment length polymorphism types of their penicillin binding protein genes 1A, 2X, and 2B. When tested in a mouse model of virulence, isolates expressing capsular type 3 were lethal for 100% of infected animals within 2 days after intraperitoneal injection of 10(2) cfu/mouse. In contrast, several capsular type 23F isolates belonging to the MDR Spanish/USA clone and recovered from the same site were not lethal, even when injected at the dose of 10(7) cfu/mouse. These data suggest that the pneumococcal isolates expressing serotypes 9N, 14, 19F, and 3 represent products of in vivo capsular transformation events in which the MDR epidemic capsular type 23F Spanish/USA clone was the recipient.
Animals↗
Molecular epidemiology of methicillin-resistant Staphylococcus aureus in 12 New York hospitals. MRSA Collaborative Study Group.
Consecutive single-patient methicillin-resistant Staphylococcus aureus (MRSA) isolates (270) from 12 hospitals (8217 beds) in metropolitan New York City were collected during May 1996. In 11 of 12 hospitals, MRSA was most frequent in the general medical services. DNA typing ("fingerprinting") revealed that mecA:Tn554:PFGE (pulsed-field gel electrophoresis) type I:A:A accounted for 113 (42%) of 270 isolates, was detected in all hospitals, and was the predominant clone in 9. Thirteen of 15 I:E:F isolates were from 1 hospital, and the remaining 2 were from another hospital of the same health system. Type V:NH:E was isolated from 22 (79%) of the 28 patients with AIDS, including 8 of 9 patients from an additional hospital. Subtype V:NH:E2 was recovered from 11 patients, 9 of whom had AIDS, including all 5 AIDS patients from one floor of a nursing home affiliated with a third hospital. By using both mecA:Tn554 probes and PFGE, MRSA clusters and outbreaks may be detected and provide a rationale for appropriate infection control intervention.
Adolescent↗
Why have group A streptococci remained susceptible to penicillin? Report on a symposium.
In spite of 50 years of extensive use of penicillin, group A streptococci remain exquisitely susceptible to this antibiotic. This observation that continuing susceptibility has occurred despite the development of resistance to other antimicrobial agents prompted a day-long meeting at Rockefeller University (New York) in October 1996. Among the most likely explanations for this remarkable state of continued susceptibility to penicillin are that beta-lactamase may not be expressed or may be toxic to the organism and/or that low-affinity penicillin-binding proteins either are not expressed or render organisms nonviable. Other potential explanations are that circumstances favorable for the development of resistance have not yet occurred and/or that there are inefficient mechanisms for or barriers to genetic transfer. Recommended future actions include (1) additional laboratory investigations of gene transfer, penicillin-binding proteins, virulence factors, and homeologous recombination and mismatch repair; (2) increased surveillance for the development of penicillin resistance; (3) application of bioinformatics to analyze streptococcal genome sequences; and (4) development of vaccines and novel antimicrobial agents. Thus far the susceptibility of group A streptococci to penicillin has not been a major clinical or epidemiological problem. A similar observation, however, could have been made decades ago about Streptococcus pneumoniae. It is therefore vital for the scientific community to closely examine why penicillin has remained uniformly highly active against group A streptococci in order to maintain this desirable state.
Humans↗
Suppression of glycopeptide resistance in a highly teicoplanin-resistant mutant of Staphylococcus aureus by transposon inactivation of genes involved in cell wall synthesis.
The teicoplanin-resistant laboratory mutant TNM of Staphylococcus aureus strain COL (minimal inhibitory concentration for teicoplanin increased from 3 to 200 microg/ml) produced an abnormal peptidoglycan in which the proportion of cross-linked oligomeric muropeptides (pentameric and higher than pentameric species), representing approximately 60% of all muropeptide species in the parental strain, was reduced to approximately 17% in the mutant. In parallel, there was an increase in the representation of the monomeric muropeptides from 4% (in the parent) to 20% in the resistant strain. The mutant cell wall showed greatly increased porosity for the detergent extraction of cytoplasmic proteins, and this property was abolished in a Tn551 insertional derivative of TNM, which was selected for reduced (parental level) teicoplanin resistance. Transposon inactivation of the global regulatory genes Sigma-B and sar, and several genes involved in early steps of staphylococcal peptidoglycan synthesis, all caused extensive reduction of teicoplanin resistance in mutant TNM, in some cases to levels close to or below the MIC value of the parental strain.
Anti-Bacterial Agents↗
Molecular epidemiologic characterization of penicillin-resistant Streptococcus pneumoniae invasive pediatric isolates recovered in six Latin-American countries: an overview. PAHO/Rockefeller University Workshop. Pan American Health Organization.
The Pan American Health Organization (PAHO) has conducted a study of Streptococcus pneumoniae in six Latin-American countries: Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay. Sterile site isolates from children aged < or =5 years showing clinical symptoms of pneumonia (as defined by the clinical criteria of WHO), meningitis, sepsis or bacteremia (without infectious foci), arthritis, and peritonitis were the source of most of the invasive pneumococcal isolates collected between the end of 1993 and 1996 in the six participating countries. Partial characterization of these isolates (antibiotic resistance and serotyping) have already been described (Microbial Drug Resistance 3:(2):131-163, 1997). In the next phase of the study, 326 S. pneumoniae isolates with reduced penicillin susceptibility were transferred to the Laboratory of Microbiology at The Rockefeller University for molecular characterization, and a summary and overview of the findings is described in this article. Some of the most interesting findings were as follows: (1) There was a surprisingly high representation of two internationally spread clones, which made up >80% of the strains with penicillin MIC of 1 microg/ml or higher; most of these isolates were recovered in large cities, supporting the likelihood that the source of these clones is through international travel. (2) The frequency of resistance to trimethoprim/sulfamethoxazole was extremely high (present in 85% of all isolates with decreased penicillin susceptibility). (3) None of these isolates was resistant to ofloxacin, and macrolide resistance was rare (present in 6.4% of the isolates). (4) There was an apparent inverse relationship between level of penicillin resistance and genetic diversity. (5) There were striking differences in the "microbiologic profiles" of the six different Latin-American countries.
Child↗
Geographic distribution of penicillin resistance of Streptococcus pneumoniae in Brazil: genetic relatedness.
From January 1993 through December 1996, 1,252 Streptococcus pneumoniae strains from different geographic regions of Brazil were studied for penicillin (Pen) susceptibility. All pneumococci were isolated from normally sterile fluids from patients, newborns to 88 years old. Pen resistance (R) had a mean rate of 15.1%, with 14.5% of strains showing intermediate level Pen-R and 0.6% showing high-level Pen-R. Similar Pen-R rates were observed in different regions of the country, in the range of 9.5% to 17.1%. A Pen-R increase was noted from 9.6% in 1993 to 20.6% in 1996. Pen-R was mostly associated to serotypes 6B, 14, 19A, and 23F (89%). Chromosomal DNA relatedness of Pen-R strains was determined by pulsed field gel electrophoresis (PFGE). High genetic diversity was identified, being represented by 27 patterns among the 92 strains. Two important features were observed: the predominance of relatively low-level Pen MIC (range 0.1-0.5 mg/L) in 86 of the 92 strains, and the presence of 60.8% as four major PFGE clusters unique to Brazil. Another feature was the geographic spread of these clusters over large distances in the country. The city of São Paulo seems to be a Pen-R focus (18.4%) in Brazil. Only two strains representing the international clone B widely spread in France, Portugal, and Spain, belonging to serotype 14, were found.
Brazil↗
The apparent importation of penicillin-resistant capsular type 14 Spanish/French clone of Streptococcus pneumoniae into Uruguay in the early 1990s.
Since 1987, Streptococcus pneumoniae (SPN) has been monitored in pediatric and adult populations. In 1994, the SIREVA/PAHO surveillance allowed the assessment of a dramatic increase of penicillin resistance, mainly associated to SPN type 14 also resistance to trimethoprim/sulfamethoxazole. To determine the genetic relatedness of the resistant isolates, analysis of SmaI digests of 61 isolates was performed by pulsed field gel electrophoresis (PFGE). Twelve different profiles were identified. The type 14 resistant SPN (n = 47) displayed a common B pattern, with 15 genetically related subtypes (1-6 bands of difference), with B1 the predominant one (51%). One of the subtypes (B12) was indistinguishable from a French isolate (M13P). This strain represented a South European clone, identified in the late 1980s, that also included serogroup 9 isolates. The type 23F isolates (n = 3) were identical with a representative strain of the well-characterized intercontinental type 23F clone. Neither the type 14 penicillin-susceptible (n = 4) nor the resistant SPN of other serotypes (n = 10) belonged to the B pattern. In summary, the results suggest that the dramatic increase of penicillin resistance in Uruguay depends on the introduction and spread of a type 14 clone, apparently imported from the south of Europe. Follow-up of this phenomenon is mandatory from the point of view of epidemiology and is also a priority for biologic research.
Electrophoresis, Gel, Pulsed-Field↗
Penicillin-resistant Streptococcus pneumoniae in Argentina: frequent occurrence of an internationally spread serotype 14 clone.
Six Latin-American countries participated in an epidemiological surveillance study conducted by the Pan American Health Organization in order to determine the relative prevalence of capsular types and antimicrobial resistance patterns of Streptococcus pneumoniae (SPN) causing invasive infections in children <5 years of age. In Argentina, the incidence of penicillin resistance (PR) was 24.4%, and it was significantly associated with serotype 14 (p < 0.001). The chromosomal DNA of 56 of those SPN isolates, 39 PR and 17 susceptible, was digested with SmaI and resolved by PFGE. Eighty-two percent (32/39) of the PR isolates shared characteristics with the widely spread International Spanish/French clone (clone B). All members of clone B except one expressed serotype 14, with the exception of one isolate that expressed serotype 19F and probably resulted from an in vivo capsular transformation event. Only a single isolate shared features with the 23F International Spanish/USA clone (clone A). The 17 penicillin-susceptible (PS) SPN isolates presented an enormous degree of variation in the chromosomal background, expressing 12 serotypes and 13 PFGE patterns. The data suggest that over 80% of the SPN-PR isolates in Argentina were imported, and this confirms the importance of the geographic spread of SPN clones in South America.
Argentina↗
Penicillin-resistant Streptococcus pneumoniae in Colombia: presence of international epidemic clones. Colombian pneumococcal study group.
The global spread of multidrug-resistant Streptococcus pneumoniae clones is well documented in the literature. A study to determine type distribution and antimicrobial susceptibility of invasive pneumococcal isolates from Colombian children under the age of 5 was conducted from 1994 to 1996. Health centers in Santa Fe de Bogota, Medellin, Cali, and other cities collected 409 Streptococcus pneumoniae isolates. Diminished susceptibility to penicillin (DSP) was 15.6%; from these, 11.5% showed intermediate-level resistance (ILR) and 4.1% showed high-level resistance (HLR). Fifty-nine of the DSP isolates were examined by pulse field gel electrophoresis (PFGE). Capsular isolate types were 23F (54%), 14 (24%), 19F (10%), 6B (7%), 9V (3%), and 34 (2%). PFGE analysis revealed that 8 isolates shared the Spanish/USA international clone's characteristic features: PFGE pattern type A, serotype 23F; 87.5% exhibited HLR for penicillin, and all were resistant to trimethoprim/sulfamethoxazole (TMP-SMX), tetracycline, and chloramphenicol. Another 7 isolates showed the French/Spanish international clone's features: PFGE pattern type B, 2 of them being serotype 9V; and 5 type 14; HLR to penicillin was 71%, and all proved resistant to TMP-SMX. A large cluster of 24 isolates (41% of all isolates examined) shared a common PFGE type C, with 14 subtypes; all but one, serotype 34, were serotype 23F and had ILR to penicillin; 58% were resistant to TMP-SMX and 50% to tetracycline, but none presented erythromycin or chloramphenicol resistance. The remaining 20 isolates could be grouped into 12 different PFGE types; ILR was shown in 75% of isolates, 70% were resistant to TMP-SMX and to tetracycline, 15% were resistant to erythromycin, and none were resistant to chloramphenicol. These data suggest that some Colombian isolates are clonally related to two of the well-known international epidemic S. pneumoniae clones.
Colombia↗
Predominance of the multiresistant 23F international clone of Streptococcus pneumoniae among isolates from Mexico.
During a surveillance study to determine the relative prevalence of capsular types of Streptococcus pneumoniae and antimicrobial susceptibility of invasive isolates in children <5 years old in Mexico City, 220 isolates were collected. The serotype 23F was the most common found, followed by types 6A + B, 14, 19F, and 19A. Diminished susceptibility to penicillin was detected in 106 isolates (48.2%), and high penicillin resistance was found in 49 strains (22.2%), 31 belonging to type 23F. Resistance was also observed to erythromycin (13.1%), to chloramphenicol (43.1%), and to cefotaxime (10.9%). No strains were resistant to ofloxacin or vancomycin. Forty-four of the highly penicillin resistant isolates (penicillin MIC > or =2.0 microg/ml) were examined with molecular fingerprinting techniques; 29 (65.9%) of these isolates (all except two strains) were serotype 23F and shared subtype variants of PFGE type A characteristic of the internationally spread Spanish/USA clone of S. pneumoniae. These strains were also resistant to trimethoprim/sulfametoxasole (TMP/SMX), chloramphenicol, and tetracycline, and most of them were susceptible to erythromycin. Another 6 of the highly penicillin-resistant strains (serogroups 9 and 14) showed PFGE fingerprints and antimicrobial susceptibility pattern characteristic of a second internationally spread clone (French/Spanish clone) and carried resistance to penicillin and TMP/SMX. The rest of the 9 penicillin-resistant isolates were represented by 7 distinct additional PFGE types. The findings suggest that almost 80% of all highly penicillin resistant strains may have been "imported" into Mexico.
Child, Preschool↗
Molecular characterization of penicillin-resistant Streptococcus pneumoniae isolates causing respiratory disease in the United States.
Three hundred twenty-eight (328) penicillin-resistant Streptococcus pneumoniae isolates collected in 39 states of the United States between October, 1996, and March, 1997, from (mostly adult) patients with respiratory disease were characterized by microbiological, serological, and molecular fingerprinting techniques, including determination of chromosomal macrorestriction pattern with pulsed-field gel electrophoresis (PFGE) and hybridization with DNA probes specific for various antibiotic resistance genes. The overwhelming majority of the isolates were in five serogroups (23, 6, 19, 9, 14). All isolates had penicillin MIC values of at least 2 microg/ml, but the collection also included isolates with MIC values as high as 16 microg/ml. Virtually all isolates (96.6%) were resistant to trimethoprim/sulfamethoxazole (SXT) and many isolates were also resistant to chloramphenicol (43%), tetracycline (55%), and erythromycin (65%). Resistance to levofloxacin was extremely rare. The molecular fingerprinting methods showed that a surprisingly large proportion (167 out of 328, or 50.9%) of the isolates belonged to two international epidemic clones of S. pneumoniae: clone A (127, or 38.7%) with properties indistinguishable from that of the 23F multiresistant "Spanish/USA" clone widely spread in Europe, Asia, Latin America, and South Africa, and clone B (40, or 12.2%) belonging to the "French" serogroup 9/14 clone widely spread in Europe and South America. Virtually all members of clone A were also resistant to chloramphenicol (cat+), tetracycline (tetM+), and SXT, and about 75% were also resistant to erythromycin (mefE+ or ermB+). Close to 30% (39 out of 127) of the clone A isolates expressed anomalous serotypes (primarily serotypes 19 and 14, and nontypable) and most likely represented spontaneous capsular transformants. Most of the 40 isolates (35/40) belonging to clone B expressed serotype 9, with five of the isolates expressing serotypes 14 or 19, or were nontypable. All members of this clone were resistant to penicillin and SXT with only occasional isolates showing resistance to macrolides, tetracycline, and chloramphenicol. The combination of microbiological tests and DNA hybridizations also allowed the identification of unusual strains, for instance, isolates that reacted with the tetM or mefE DNA probes without showing phenotypic antibiotic resistance, an isolate showing phenotypic macrolide resistance without hybridizing with either the ermB or mefE DNA probes, or isolates that hybridized with both of these DNA probes. In addition to clones A and B, another large portion of the S. pneumoniae isolates (112 of 328, or 34.1%) was represented by eight clusters, each with a unique PFGE type. These clusters, together with the clone A and clone B isolates, made up 85% of all the penicillin-resistant isolates identified in this survey in the United States. Both international clones and the unique clusters showed wide geographic dispersal: Clone A was present in 30 of the 39 states and clone B in 18. The data suggest that the major mode of spread of penicillin-resistant pneumococci in the United States is by clonal expansion and that the most significant components (clones A and B) have been imported into the United States from abroad.
Adult↗
Antibacterial efficacy of nisin against multidrug-resistant Gram-positive pathogens.
The rapid spread of multidrug-resistant bacterial pathogens necessitates the search for alternative antibacterial agents. We examined the efficacy of the antibiotic nisin against 56 multidrug-resistant isolates of Streptococcus pneumoniae, 33 Staphylococcus aureus and 29 vancomycin-resistant Enterococcus faecium and Enterococcus faecalis isolates. The test strains represented a large variety of clonal types (as determined by a combination of DNA fingerprints) isolated from a variety of geographic sources, and included some of the major internationally-spread multiresistant epidemic clones of S. pneumoniae and methicillin-resistant S. aureus (MRSA), MRSA strains resistant to over 16 generically distinct antibacterial agents, and enterococcal strains resistant to all currently available chemotherapeutic agents including glycopeptides. In the overwhelming majority of cases, treatment of growing cultures with nisin at 1 mg/L (S. pneumoniae) or 10-20 mg/L (in MRSA and enterococci) caused extensive (10(3)- to 10(4)-fold) loss of viable titre accompanied by various degrees of loss in the optical density of the cultures, which was most extensive in pneumococci (>90%) and least extensive (40-50%) in enterococci. Nevertheless, extensive variation in rates of nisin-induced autolysis was observed in each bacterial species. Serial exposure of a penicillin-susceptible strain of S. pneumoniae to nisin (1 mg/L) in liquid culture resulted in the rapid appearance of stable nisin-resistant mutants in which the MIC increased from 0.4 to 6.4 mg/L and the resistance trait was transferable by genetic transformation.
Anti-Bacterial Agents↗