Teicoplanin Resistance Research Articles

Heterogeneous glycopeptide intermediate Staphylococcus epidermidis isolated from prosthetic joint infections

Methicillin-resistant Staphylococcus epidermidis (MRSE) poses a major problem in prosthetic joint infections (PJIs). Vancomycin is often considered the drug of choice in the empirical treatment of staphylococcal PJIs. As recent decades have seen reports of heterogeneous glycopeptide intermediate S. aureus (hGISA), our aim was to examine the prevalence of heterogeneous glycopeptide intermediate S. epidermidis (hGISE) in PJIs. S. epidermidis isolates (n = 122) from 119 patients in three Swedish counties between 1993 and 2012 were included. All were isolated from perioperative tissue samples from revision surgery in clinically verified PJIs. Antimicrobial susceptibility testing against staphylococcal antibiotics was performed. The macromethod Etest (MME) and glycopeptide resistance detection (GRD) Etest were used to detect hGISE. Standard minimal inhibitory concentration (MIC) determination revealed no vancomycin-resistant isolates, while teicoplanin resistance was detected in 14 out of 122 isolates (11.5%). hGISE was found in 95 out of 122 isolates (77.9%), 64 out of 67 of isolates with teicoplanin MIC >2 mg/L (95.5%) and 31 out of 55 of isolates with teicoplanin MIC ≤2 mg/L (56.4%). Thus, the presence of hGISE cannot be ruled out by teicoplanin MIC ≤2 mg/L alone. Multidrug resistance was detected in 86 out of 95 hGISE isolates (90.5%) and in 16 out of 27 isolates (59.3%), where hGISE could not be detected. In conclusion, hGISE detected by MME or GRD was common in this material. However, hGISE is difficult to detect with standard laboratory diagnostic routines. Glycopeptide treatment may not be sufficient in many of these PJIs, even if standard MIC classifies the isolated S. epidermidis as susceptible.

ICE Slu van, a 94-Kilobase Mosaic Integrative Conjugative Element Conferring Interspecies Transfer of VanB-Type Glycopeptide Resistance, a Novel Bacitracin Resistance Locus, and a Toxin-Antitoxin Stabilization System

A 94-kb integrative conjugative element (ICESluvan) transferable to Enterococcus faecium and Enterococcus faecalis from an animal isolate of Streptococcus lutetiensis consists of a mosaic of genetic fragments from different Gram-positive bacteria. A variant of ICESluvan was confirmed in S. lutetiensis from a patient. A complete Tn5382/Tn1549 with a vanB2 operon is integrated into a streptococcal ICESde3396-like region harboring a putative bacteriophage exclusion system, a putative agglutinin receptor precursor, and key components of a type IV secretion system. Moreover, ICESluvan encodes a putative MobC family mobilization protein and a relaxase and, thus, in total has all genetic components essential for conjugative transfer. A 9-kb element within Tn5382/Tn1549 encodes, among others, putative proteins similar to the TnpX site-specific recombinase in Faecalibacterium and VanZ in Paenibacillus, which may contribute to the detected low-level teicoplanin resistance. Furthermore, ICESluvan encodes a novel bacitracin resistance locus that is associated with reduced susceptibility to bacitracin when transferred to E. faecium. The expression of a streptococcal pezAT toxin-antitoxin-encoding operon of ICESluvan in S. lutetiensis, E. faecium, and E. faecalis was confirmed by reverse transcription (RT)-PCR, indicating an active toxin-antitoxin system which may contribute to stabilizing ICESluvan within new hosts. Junction PCR and DNA sequencing confirmed that ICESluvan excised to form a circular intermediate in S. lutetiensis, E. faecalis, and E. faecium. Transfer between E. faecalis cells was observed in the presence of helper plasmid pIP964. Sequence analysis of the original S. lutetiensis donor and enterococcal transconjugants showed that ICESluvan integrates in a site-specific manner into the C-terminal end of the chromosomal tRNA methyltransferase gene rumA.

Genomic analysis of teicoplanin resistance emerging during treatment of vanB vancomycin-resistant Enterococcus faecium infections in solid organ transplant recipients including donor-derived cases

We noted four cases of apparent in vivo emergence of teicoplanin resistance during failed therapy for initially teicoplanin-susceptible vanB vancomycin-resistant Enterococcus faecium (VREfm) infections in solid organ transplant recipients at our institution over a 12 month period. We investigated if in vivo emergence of resistance had occurred, if transplant-related vancomycin-resistant Enterococcus (VRE) infections had occurred and identified clinical predictors of resistance emergence. Whole genome sequencing was performed on nine VREfm isolates for phylogenetic analysis and to identify determinants of teicoplanin resistance. Clinical treatment details were compared with other patients who received teicoplanin for confirmed vanB VRE infections but did not develop resistance during the same year at our institution. A high-resolution, core genome phylogeny was inferred for nine VREfm isolates and confirmed in vivo development of resistance during failed therapy in four cases. Four different non-synonymous single nucleotide polymorphisms (SNPs) were observed in the vanRS genes of teicoplanin-resistant strains compared with the index teicoplanin-susceptible strains, and these SNPs were predicted to confer teicoplanin resistance. VREfm within a cluster of early transplant-related infections were phylogenetically identical at the core genome level, indicating a common source donor. Focus eradication and absence of prosthetic material were characteristics of those patients treated successfully. Clinicians should be cautious of resistance emerging during teicoplanin therapy for vanB VRE, particularly in immunosuppressed patients or where source control is difficult.

Vancomycin-resistente Enterokokken (VRE)

Enterococci (mainly E. faecalis, E. faecium) are important nosocomial pathogens predominantly affecting older and/or immunocompromised patients. The bacteria possess a broad spectrum of intrinsic and acquired antibiotic resistance properties. Among these, the transferrable glycopeptide resistance of the vanA and vanB genotypes in vancomycin-resistant enterococci (VRE; reservoir: E. faecium) as well as resistance to last resort antibiotics (e.g. linezolid and tigecycline) are of special concern. Enterococci (including VRE) are easily transferred in hospitals; however, colonizations are far more frequent than infections. Resistance frequencies for vancomycin in clinical E. faecium isolates have remained at a relatively constant level of 8–15% (but with local or regional variations) in recent years whereas frequencies for teicoplanin resistance have shown a slight decrease. Glycopeptide resistance trends correlate with a spread of hospital-associated E. faecium strains carrying the vanA and, with rising frequency in recent years, the vanB gene cluster, the latter being associated with teicoplanin susceptibility. This increased occurrence of vanB-positive E. faecium strains may be caused by an increased use of antibiotics selecting enterococci and VRE as well as due to methodological reasons (e.g. reduced EUCAST MIC-breakpoints for glycopeptides; increased use and sensitive performance of chromogenic VRE agars, increased use of molecular diagnostic assays).

Prevalence of isolates with reduced glycopeptide susceptibility in orthopedic device-related infections due to methicillin-resistant Staphylococcus aureus

We evaluated, by an improved susceptibility testing method, the prevalence and significance of low-level glycopeptide resistance in methicillin-resistant Staphylococcus aureus (MRSA) isolates, which belonged to a previously described, retrospective cohort of patients treated for orthopedic device-related infections (ODRI) at the Geneva University Hospital between 2000 and 2008. Fifty-seven individual or multiple isolates were retrieved from 41 ODRI patients for glycopeptide susceptibility and clonality studies, including 20 patients with prosthetic joint (PJ) and 21 with osteosynthesis (OS) MRSA infections. Low-level glycopeptide resistance was detected by elevated teicoplanin or/and vancomycin minimum inhibitory concentrations (MICs ≥ 4 mg/L), as determined by a previously validated combination of macrodilution and agar dilution assays of improved sensitivity. MRSA isolates with elevated teicoplanin MICs were detected in 20/41 (49 %) ODRI patients at the onset or during the course of glycopeptide therapy, namely, in 10 of 20 patients with PJ and 10 of 21 patients with OS infections. Only one isolate developed a concomitant increase in vancomycin MIC during therapy. 13/20 (65 %) glycopeptide-intermediate S. aureus (GISA)-infected patients, including 7/10 (70 %) with PJ and 6/10 (60 %) with OS, experienced treatment failure. In contrast, therapy failed in only 5/21 (24 %) ODRI patients with non-GISA isolates (p = 0.012), including 2/10 (20 %) with PJ and 3/11 (27 %) with OS infections. The emergence of low-level teicoplanin resistance could not be explained by teicoplanin administration, since only four patients received teicoplanin. The evaluation of low-level teicoplanin resistance may improve the detection of GISA isolates. Further studies are warranted to evaluate the impact of low-level teicoplanin resistance on the outcome of glycopeptide therapy.

A Novel Membrane Protein, VanJ, Conferring Resistance to Teicoplanin

Bacterial resistance to the glycopeptide antibiotic teicoplanin shows some important differences from the closely related compound vancomycin. They are currently poorly understood but may reflect significant differences in the mode of action of each antibiotic. Streptomyces coelicolor possesses a vanRSJKHAX gene cluster that when expressed confers resistance to both vancomycin and teicoplanin. The resistance to vancomycin is mediated by the enzymes encoded by vanKHAX, but not by vanJ. vanHAX effect a reprogramming of peptidoglycan biosynthesis, which is considered to be generic, conferring resistance to all glycopeptide antibiotics. Here, we show that vanKHAX are not in fact required for teicoplanin resistance in S. coelicolor, which instead is mediated solely by vanJ. vanJ is shown to encode a membrane protein oriented with its C-terminal active site exposed to the extracytoplasmic space. VanJ also confers resistance to the teicoplanin-like antibiotics ristocetin and A47934 and to a broad range of semisynthetic teicoplanin derivatives, but not generally to antibiotics or semisynthetic derivatives with vancomycin-like structures. vanJ homologues are found ubiquitously in streptomycetes and include staP from the Streptomyces toyocaensis A47934 biosynthetic gene cluster. While overexpression of staP also conferred resistance to teicoplanin, similar expression of other vanJ homologues (SCO2255, SCO7017, and SAV5946) did not. The vanJ and staP orthologues, therefore, appear to represent a subset of a larger protein family whose members have acquired specialist roles in antibiotic resistance. Future characterization of the divergent enzymatic activity within this new family will contribute to defining the molecular mechanisms important for teicoplanin activity and resistance.

Central Venous Catheter-related Blood Stream Infections in Children Undergoing Hematopoietic Stem Cell Transplant for Primary Immunodeficiency and Other Nonmalignant Disorders

A single-center experience of catheter-related blood stream infections in children undergoing hematopoietic stem cell transplant for primary immunodeficiency is described. The rate of definite central venous catheter infections was 5.31/1000 line days. Staphylococcus epidermidis was the most commonly identified organism. Teicoplanin resistance occurred in 17% of S. epidermidis infections. The central catheter was removed in 21% of infections.

Detection and genetic characterisation of vanA‐containing Enterococcus strains in healthy Lusitano horses

Lusitano horses were investigated in order to detect the presence of vancomycin-resistant enterococci. vanA isolates showed high level vancomycin (Minimum inhibitory concentration; MIC > or = 128 mg/l) and teicoplanin resistance (MIC 64 mg/l), as well as resistance to ciprofloxacin, erythromycin and tetracycline. The tet(L) and erm(B) genes, associated with tetracycline and erythromycin resistance, respectively, were found in all vanA isolates. The intestinal tract of Lusitano horses can be a potential reservoir for vanA-containing enterococci.

Identification by Genomic and Genetic Analysis of Two New Genes Playing a Key Role in Intermediate Glycopeptide Resistance in Staphylococcus aureus

Endogenous, low-level glycopeptide resistance in Staphylococcus aureus results from multifactorial genetic changes. Comparative genomic hybridization analysis revealed the specific deletion of a 1.8-kb segment encompassing two adjacent open reading frames (ORFs) of unknown function in a teicoplanin-susceptible revertant (strain 14-4rev) compared to the sequence of its isogenic, teicoplanin-resistant parental strain, strain 14-4. This provocative finding prompted us to perform a detailed genetic analysis of the contribution of this genomic segment to glycopeptide resistance. Despite repeated efforts in our laboratory, 14-4 and 14-4rev have proven refractory to most genetic manipulations. To circumvent this difficulty, we evaluated the contribution of both putative ORFs (designated teicoplanin resistance factors trfA and trfB) on teicoplanin resistance in a different, genetically tractable background. Genetic analysis showed that single or double trfA and/or trfB mutations abolished teicoplanin resistance in two independent teicoplanin-resistant derivatives of NCTC8325 strain ISP794 generated by two-step passages with the drug. The frequency of teicoplanin-resistant mutants was markedly decreased by the absence of trfAB in the teicoplanin-susceptible ISP794 background. Nevertheless, a low rate of teicoplanin-resistant mutants was selected from ISP794 trfAB, thus indicating an additional contribution of trfAB-independent pathways in the emergence of low-level glycopeptide resistance. Further experiments performed with clinical glycopeptide-intermediate S. aureus isolate NRS3 indicated that the trfAB mutation could affect not only teicoplanin resistance but also vancomycin and oxacillin resistance. In conclusion, our study demonstrates the key role of two novel loci in endogenous, low-level glycopeptide resistance in S. aureus whose precise molecular functions warrant further investigation.

VanB Phenotype- vanA Genotype Enterococcus faecium with Heterogeneous Expression of Teicoplanin Resistance

Six VanB phenotype-vanA genotype isolates of Enterococcus faecium with heterogeneous expression of teicoplanin resistance which gave rise to an outbreak at a Korean tertiary care teaching hospital have IS1216V in the coding region of vanS. This could be the underlying cause of the VanB phenotype-vanA genotype with heterogeneous expression of teicoplanin resistance.

Teicoplanin pharmacodynamics in reference to the accessory gene regulator (agr) in Staphylococcus aureus using an in vitro pharmacodynamic model

The accessory gene regulator (agr) has been identified as playing a role in the expression of reduced glycopeptide susceptibility in Staphylococcus aureus. Previous studies indicate that strains with agr dysfunctional group II polymorphism have a higher propensity for reduced vancomycin activity. We investigated this relationship in agr groups I-IV using another glycopeptide, teicoplanin, in an in vitro pharmacodynamic model. Teicoplanin doses ranging from 1.88 to 30 mg/kg daily (fAUC/MIC 26.1-380.7) were simulated and evaluated for activity and the development of reduced susceptibility over 72 h. A dose-response relationship in activity was noted as doses escalated up to 30 mg/kg daily, but regrowth was identified with all doses. Teicoplanin doses of 3.75 and 1.88 mg/kg daily resulted in isolates with intermediate teicoplanin susceptibility (MIC = 16 mg/L) in agr groups II, IV (MIC = 16 mg/L) and III (MIC = 24 mg/L), regardless of function of the agr operon. Resistance to teicoplanin (> or = 32 mg/L) occurred in agr group I functional and dysfunctional isolates. Minimal changes in MIC were noted with 7.5 mg/kg daily doses in agr groups II-IV. However, this dose resulted in variable susceptibility (4-24 mg/L) in agr group I(+/-) isolates. Higher doses of 15 and 30 mg/kg daily did not produce changes in MIC in any isolate tested. Agr function did not determine teicoplanin resistance proclivity and is consistent with the previously described higher mutation rate in S. aureus to teicoplanin. Further investigation of agr group and function is warranted for all glycopeptides and compounds with a similar mechanism of action.

Functional Characterization of TcaA: Minimal Requirement for Teicoplanin Susceptibility and Role in Caenorhabditis elegans Virulence

The inactivation of TcaA contributes to intrinsic teicoplanin resistance in experimental and clinical isolates of glycopeptide-intermediate resistant Staphylococcus aureus. PhoA fusions confirmed that TcaA is a transmembrane protein with a short intracellular N-terminal domain containing a C-4 zinc finger binding motif, a single membrane-spanning domain, and a large extracellular C-terminal domain. The region conferring teicoplanin susceptibility was narrowed down to the transmembrane part and the first third of the extracellular domain of TcaA, suggesting that neither the C-4 zinc finger binding motif nor the C terminus contributed to teicoplanin susceptibility. TcaA belongs to the cell wall stress stimulon, which comprises a set of genes universally upregulated by cell wall damage. Induction of tcaA was shown to be fully dependent on the two-component regulatory system VraSR. A 66-bp region upstream of the transcriptional start site, which contained an inverted repeat partially covering the promoter box, was shown to be essential for VraSR-mediated induction by cell wall stress. Interestingly, the induction or overexpression of tcaA did not contribute further to teicoplanin susceptibility, suggesting that small amounts of TcaA, such as those present under normal uninduced conditions, were sufficient for TcaA-mediated teicoplanin susceptibility. The strong attenuation of tcaA deletion mutants in a Caenorhabditis elegans survival assay suggested that TcaA may, in addition to affecting glycopeptide susceptibility, also play a role in virulence.

Vancomycin-resistant Enterococci, Mexico City

Vancomycin-resistant Enterococci, Mexico City

Role of insertion elements and yycFG in the development of decreased susceptibility to vancomycin in Staphylococcus aureus

The glycopeptide antibiotic vancomycin acts by binding to the D-alanyl- D-alanine terminus of the cell wall precursor lipid II in the cytoplasmic membrane. The purpose of this study was the identification of genes that might be involved in the vancomycin resistance mechanism. To this end, the expression profiles of two vancomycin intermediately resistant Staphylococcus aureus (VISA) strains, the clinical isolate S. aureus SA137/93A (Etest: 8 μg/ml) and its laboratory mutant S. aureus SA137/93G (Etest: 12 μg/ml) were analyzed using an S. aureus full-genome chip. The results indicated that an essential two-component regulatory system, yycF ( vicR) and yycG ( vicK) was drastically up-regulated in strain SA137/93A. Sequencing of the yycFG promoter region of strain SA137/93A revealed an insertion of IS 256 in the predicted promoter region creating a potentially stronger hybrid promoter. In strain SA137/93G, IS 256 was not integrated in the yycFG promoter region but, in previous studies, a copy of IS 256 had been found to inactivate the tcaA gene (Maki et al. Antimicrob. Agents and Chemother. 48, 1953–1959 (2004)). Detailed population analyses showed that, in addition to the loss of SCC mec, the inactivation of tcaA seems to cause at least part of the increase in teicoplanin and vancomycin resistance in strain SA137/93G.

Linezolid Therapy of Bloodborne Teicoplanin-Resistant Staphylococcus haemolyticus

Coagulase-negative staphylococci (CNS) are human skin commensals, but are now also recognized as an important cause of foreign-device infections and nosocomial bacteremia [1, 2]. Staphylococcus epidermidis is the CNS species most frequently identified, followed by Staphylococcus haemolyticus, which accounts for about 10% of isolates [3]. Glycopeptides – vancomycin or teicoplanin (available in almost all European countries) – are the drugs of choice for these infections, as CNS isolated in hospitals are frequently resistant to methicillin. Diminished susceptibility and resistance to glycopeptides are both rare but have been reported in Staphylococcus aureus [4] and S. haemolyticus [5]. S. haemolyticus is an important nosocomial pathogen with a tendency to develop multiple antibiotic resistance. Linezolid is a new antibiotic licensed for the treatment of staphylococcal infections, but clinical experience in the therapy of CNS infections has been limited [6]. We describe a case of S. haemolyticus bacteremia in which teicoplanin resistance developed during treatment and which was successfully treated with linezolid. A 62-year-old woman with no past medical history was diagnosed with acute myeloid leukemia in June 2004. Fourteen days after starting the third course of chemotherapy she developed febrile neutropenia, for which she received intravenous empiric antibiotic therapy with piperacillintazobactam and ofloxacin. Clinical efficacy was poor, and two sets of blood cultures yielded a coagulase-negative Staphylococcus isolate that was identified as S. haemolyticus by using the API test system (bioMerieux, Marcy l’Etoile, France). Initial antimicrobial sensitivity testing with the API system showed that the isolates were resistant to oxacillin but susceptible to vancomycin and teicoplanin. Intravenous teicoplanin therapy was started (400 mg/daily, after a loading dose of 400 mg bid for 2 days), as a lifethreatening allergic reaction to vancomycin had occurred during the first course of chemotherapy. Her condition continued to deteriorate despite this treatment: in particular, she remained febrile and her respiratory function deteriorated. The respiratory rate was 30 breaths/min and the oxygen saturation 91% on 10 l/min oxygen. Chest radiography showed a diffuse and worsening alveolar syndrome. After 2 days of antibiotic treatment she was transferred to the medical ICU. On admission her blood pressure was 110/60 mmHg, her heart rate 100 beats/min, and her respiratory rate 32 breaths/min. Her oxygen saturation was 95% on

In vitro susceptibility of Gram-positive pathogens to linezolid and teicoplanin and effect on outcome in critically ill patients

To determine the prevalence of teicoplanin and linezolid resistance amongst Gram-positive pathogens isolated in the intensive care unit (ICU) and the impact of any resistance on clinical outcome. Gram-positive isolates were collected from two critical care units over 1 year. All patients were screened weekly for methicillin-resistant Staphylococcus aureus (MRSA). Susceptibility to teicoplanin and linezolid was tested by Etest. The length of hospital and critical care unit stay and the use of antibiotics in each patient were recorded. Reduced susceptibility to teicoplanin (MIC>or=16 mg/L) was found in 21 [3.3% (95% CI 2.0-5.0%) 6 patients] of 643 strains of MRSA versus none of 374 methicillin-susceptible S. aureus (MSSA) [<0.3% (95% CI 0-0.9%)]. Of 49 enterococci 3 were teicoplanin-resistant. All Gram-positive isolates were susceptible to linezolid. The length of treatment with teicoplanin and outcome of patients infected with these strains were similar to that of susceptible strains. MRSA was a more common cause of infection than MSSA but a less frequent colonizer. Resistance to teicoplanin remains at a comparatively low level and there was no clear relationship between susceptibility and outcome in this critically ill population. There was no resistance in Gram-positives to linezolid but this should be kept as a reserve antibiotic to maintain its activity.

Comparison of four methods for detection of teicoplanin resistance in methicillin-resistant Staphylococcus aureus

To determine which method of determining the MIC of teicoplanin produces a result closely related to outcome in the critically ill patient. Four methods of teicoplanin susceptibility testing-disc diffusion, Etest, VITEK (Legacy and VITEK 2) and agar incorporation-were compared for 47 methicillin-resistant Staphylococcus aureus (MRSA) isolates from invasive intensive care unit (ICU) infections and 83 isolates from ICU patients colonized with the organism. Clinical outcome was recorded prospectively for all the patients. Another 13 reference laboratory strains of MRSA with reduced susceptibility to teicoplanin were tested. Both VITEK systems failed to demonstrate resistance in the three isolates identified as resistant by Etest or agar incorporation, and disc testing detected only one resistant isolate. A higher MIC, as found by Etest or agar incorporation, was associated with lower survival (n = 130, 95% CI -0.082 to -0.006, P = 0.023, Etest; n = 130, 95% CI -0.156 to -0.020, P = 0.011, agar). The findings for the 13 reference strains were similar, with a > or = 4-fold reduction in MIC between agar incorporation or Etest and VITEK2 for six isolates. Neither disc diffusion nor the VITEK systems are reliable for detection of teicoplanin resistance in MRSA. Etest and agar incorporation remain the methods of choice.

Staphylococcus aureus CcpA Affects Virulence Determinant Production and Antibiotic Resistance

Carbon catabolite protein A (CcpA) is known to function as a major regulator of gene expression in different gram-positive organisms. Deletion of the ccpA homologue (saCOL1786) in Staphylococcus aureus was found to affect growth, glucose metabolization, and transcription of selected virulence determinants. In liquid culture, deletion of CcpA decreased the growth rate and yield; however, the effect was only transient during the exponential-growth phase as long as glucose was present in the medium. Depletion of glucose and production of lactate was delayed, while the level of excretion of acetate was less affected and was even higher in the mutant culture. On solid medium, in contrast, growth of the DeltaccpA mutant resulted in smaller colonies containing a lower number of CFU per colony. Deletion of CcpA had an effect on the expression of important virulence factors of S. aureus by down-regulating RNAIII, the effector molecule of the agr locus, and altering the transcription patterns of hla, encoding alpha-hemolysin, and spa, encoding protein A. CcpA inactivation markedly reduced the oxacillin resistance levels in the highly methicillin-resistant S. aureus strain COLn and the teicoplanin resistance level in a glycopeptide-intermediate-resistant S. aureus strain. The presence of CcpA in the capsular polysaccharide serotype 5 (CP5)-producing strain Newman abolished capsule formation and decreased cap operon transcription in the presence of glucose. The staphylococcal CcpA thus not only is involved in the regulation of carbon metabolism but seems to function as a modulator of virulence gene expression as well.

The discriminatory power of MALDI-TOF mass spectrometry to differentiate between isogenic teicoplanin-susceptible and teicoplanin-resistant strains of methicillin-resistantStaphylococcus aureus

To explore the discriminatory power of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for detecting subtle differences in isogenic isolates, we tested isogenic strains of Staphylococcus aureus differing in their expression of resistance to methicillin or teicoplanin. More important changes in MALDI-TOF MS spectra were found with strains differing in methicillin than in teicoplanin resistance. In comparison, very minor or no changes were recorded in pulsed-field gel electrophoresis profiles or peptidoglycan muropeptide digest patterns of these strains, respectively. MALDI-TOF MS might be useful to detect subtle strain-specific differences in ionizable components released from bacterial surfaces and not from their peptidoglycan network.

Nosocomial Meningitis Due to Teicoplanin-Resistant Coagulase-Negative Staphylococci Complicating Ventriculoperitoneal Shunt Insertion in Children

Falcone et al. report in the Journal of Chemotherapy 1 that they found 47.5% resistance to teicoplanin in patients with bacteremia due to coagulase-negative staphylococci (CNS). We report here our data on teicoplanin resistance in CNS isolated from cerebrospinal fluid (CSF) in Slovakia. We reviewed 158 cases of nosocomial meningitis occurring in children over a 12-year period and found that 92 were caused by CNS (61%), including S. epidermidis in 82 patients and 10 other CNS (S. Journal of Chemotherapy Vol. 17 n. 5 (572) 2005