Resistant Streptococcus Research Articles

PCV7: Impact on Invasive Pneumococcal Disease and Resistant S pneumoniae

Infectious Disease| August 01 2006 PCV7: Impact on Invasive Pneumococcal Disease and Resistant S pneumoniae AAP Grand Rounds (2006) 16 (2): 13–14. https://doi.org/10.1542/gr.16-2-13 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation PCV7: Impact on Invasive Pneumococcal Disease and Resistant S pneumoniae. AAP Grand Rounds August 2006; 16 (2): 13–14. https://doi.org/10.1542/gr.16-2-13 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: invasive pneumococcal disease, pneumococcal 7-valent conjugate vaccine, streptococcus pneumoniae Sources: (1) Poehling KA, Talbot TR, Griffin MR, et al. Invasive pneumococcal disease among infants before and after the introduction of pneumococcal conjugate vaccine. JAMA. 2006;295:1668–1674; doi:10.1001/jama.295.14.1668 (2) Kyaw MH, Lynfield R, Schaffner W, et al. Effect of introduction of the pneumococcal conjugate vaccine on drug resistant Streptococcus pneumoniae. N Engl J Med. 2006;354:1455–1463; doi:10.1056/NEJMoa051642 Investigators from the Centers for Disease Control and Prevention (CDC), in collaboration with researchers from 8 states, report the effect of the heptavalent pneumococcal conjugate vaccine (PCV7) on invasive pneumococcal disease (IPD) in infants, and the resistance patterns of Streptococcus pneumoniae. In the study by Poehling et al, rates of IPD in neonates and young infants (0 to 90 days of age) before and after the introduction of PCV7 in 2000 were compared. The pre-PCV7 period assessed was 1997–1999 and the post-PCV7 period 2001–2004. All available isolates were serotyped starting in 1998. Eighty-nine infants with IPD were identified in the pre-PCV7 period and 57 in the post-PCV7 period. All were single episodes; the median age of patients was 46 days (range 0–88 days). For all 0- to 90-day-old infants, the mean IPD rate (per 100,000 live births) decreased from 11.8 (95% CI, 9.6–14.5) pre-PCV7 to 7.2 (95% CI, 5.6–9.4) post-PCV7 (P=.004). The IPD rate for 0- to 60-day-old infants also decreased significantly, even though PCV7 is not recommended for infants <2 months of age. Age, gender, type of IPD, and state from which IPD cases were identified were similar in the 2 periods. The proportion of IPD cases that occurred in black infants post-PCV7 was half that of the pre-PCV7 period, eliminating the previously observed racial difference in incidence.1 Mean IPD rates caused by PCV7 serotypes decreased significantly, but the rates for non-PCV7 serotypes remained unchanged. In the report from Kyaw et al, antibiotic susceptibilities were assessed on 24,825 S pneumoniae isolates from 28,336 adult and pediatric patients with IPD identified between January 1, 1996 and December 31, 2004. Isolates with intermediate- or high-level resistance were considered resistant. Multidrug resistance (MDR) was defined as non-susceptibility to at least 3 antibiotics. Isolates were serotyped and stratified into vaccine type, vaccine-related, and non-vaccine types. The rate of penicillin-resistant (PR) IPD decreased from its 1999 peak by 57%, from 6.3 to 2.7. Similar decreases were identified for erythromycin-resistant and MDR strains of S pneumoniae isolated in patients with IPD. Overall rates of PR-IPD due to vaccine serotypes fell from 5.0 to 0.7, an 87% decrease. Among children <5 years of age, the rate of PR-IPD ranged from 25.9 to 33.8 between 1996 and 1999 versus 7.5 in 2004. The largest decline was in children <2 years of age. Similar decreases were seen for erythromycin-resistant and MDR-IPD rates. For children <2 years of age, almost all IPD in both periods was caused by penicillin-resistant isolates that were either vaccine or vaccine-related serotypes. After the vaccine introduction, an increase in non-vaccine serotype IPD was seen in... You do not currently have access to this content.

Single nucleotide polymorphism analysis using different colored dye dimer probes

Fluorescence quenching by dye dimer formation has been utilized to develop hairpin-structured DNA probes for the detection of a single nucleotide polymorphism (SNP) in the penicillin target gene pbp2x, which is implicated in the penicillin resistance of Streptococcus pneumoniae. We designed two specific DNA probes for the identification of the pbp2x genes from a penicillin susceptible strain R6 and a resistant strain Streptococcus mitis 661 using green-fluorescent tetramethylrhodamine (TMR) and red-fluorescent DY-636, respectively. Hybridization of each of the probes to its respective target DNA sequence opened the DNA hairpin probes, consequently breaking the nonfluorescent dye dimers into fluorescent species. This hybridization of the target with the hairpin probe achieved single nucleotide specific detection at nanomolar concentrations via increased fluorescence.

Beta-lactam resistance in Streptococcus mitis isolated from saliva of healthy subjects

The percentages of healthy subjects carrying ampicillin- and cefaclor-resistant streptococci in saliva were 52% (27 of 52 subjects) and 100%, respectively. From the sequencing results of pbp1a, 2x, 2b genes, Streptococcus mitis including both ampicillin-resistant and -susceptible strains (a total of 13 strains) were divided into 5 groups. The highly resistant strains had multiple mutations in all pbp genes. By competitive assay using a fluorescent penicillin derivative, affinity of the PBPs for both ampicillin and cefaclor in the ampicillin-resistant strain reduced significantly, compared to that in the susceptible strain. These results suggest that the accumulation of the mutations in pbp genes might contribute to the beta-lactam resistance by means of coding PBPs with a low affinity for the antibiotics. Furthermore, an ampicillin-resistant strain was not completely killed even after 24 h incubation with the MIC of ampicillin against the strain (8 μg/ml) in vitro, and cefaclor at the same concentration never influenced the growth of this bacteria. Therefore, we should be aware of the increase of beta-lactam resistant streptococci in oral flora as the causative agents of penicillin-insensitive infective endocarditis.

Fluoroquinolone Resistance in Invasive Streptococcus pyogenes Isolates Due to Spontaneous Mutation and Horizontal Gene Transfer

Fluoroquinolone resistance in Streptococcus pyogenes has been described only anecdotally. In this study we describe two invasive ciprofloxacin-resistant S. pyogenes isolates (ciprofloxacin MICs, 8 mg/liter), one of which shows evidence of interspecies recombination. The quinolone resistance-determining regions of gyrA and parC were sequenced. In both isolates, there was no evidence for an efflux pump and no mutation in gyrA. Both isolates had an S79F mutation in parC that is known to confer fluoroquinolone resistance. In addition, a D91N mutation in parC, which is not related to fluoroquinolone resistance but is a feature of the parC sequence of Streptococcus dysgalactiae, was found in one isolate. The parC nucleotide sequence of that isolate showed greater diversity than that of S. pyogenes. A GenBank search and phylogenetic analysis suggest that this isolate acquired resistance by horizontal gene transfer from S. dysgalactiae. Statistical testing for recombination confirmed interspecies recombination of a 90-bp sequence containing the S79F mutation from S. dysgalactiae. For the other isolate, we could confirm that it acquired resistance by spontaneous mutation by identifying the susceptible ancestor in an outbreak setting.

Resistance to Anti-Infective Drugs and the Threat to Public Health

Increasing resistance of pathogens to anti-infective drugs is an urgent public health problem that must be addressed through more prudent use of these drugs in human medicine and in animal husbandry, agriculture, and aquaculture.

Antimicrobial Spectrum and Potency of Dalbavancin Tested Against Clinical Isolates from Europe and North America (2003): Initial Results from an International Surveillance Protocol

Dalbavancin is a bactericidal dimethylaminopropyl amide glycopeptide derivative possessing an extended serum elimination half-life in humans that allows onceweekly dosing for the therapy of Gram-positive infections. Strains from this baseline surveillance protocol in North America (NA; USA and Canada) and Europe (EU, 14 countries) were sampled in 2003. A total of 7,765 Gram-positive isolates (3,695 from NA and 4,070 from EU) were tested by reference broth microdilution methods against dalbavancin and 10 comparator agents. Species were analyzed separately by resistance phenotypes such as methicillin- (oxacillin-) resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and penicillin- resistant Streptococcus pneumoniae. Dalbavancin and other glycopeptides were very active against staphylococci (n=4648) with dalbavancin being 16- to 32- fold more potent than vancomycin (MIC90, 0.06 versus 2 mg/L). MRSA rates were greater (31.6%) in NA than in EU (26.1%). Quinupristin/dalfopristin resistance (MIC, ≥ 2 mg/L; 0.1 - 0.5%) was documented more often in EU compared to NA. Dalbavancin (MIC50, 0.03 - 0.06 mg/L) was active against enterococci, except VanA resistance phenotypes. VRE rates were lower in EU (8.3%) then in NA (35.9%) from this resistance-enhanced enterococcal collection. Streptococci (dalbavancin MIC90, 0.016 - 0.03 mg/L) were generally most susceptible to glycopeptides (100.0%), quinupristin/dalfopristin (98.6 - 100.0%) and linezolid (100.0%); but dalbavancin was 16-fold more active than comparators. All vancomycin-susceptible enterococci and > 90% of vanB VRE had dalbavancin MIC values at ≤ 1 mg/L, but vanA VRE strains had dalbavancin MIC results ranging from 0.06 to > 8 mg/L (median MIC, ≥ 8 mg/L). Dalbavancin MIC values were not adversely influenced by geographic region or resistance phenotype (except vanA VRE). Infrequently isolated Gram-positive organisms such as Bacillus spp. (MIC90, 0.12 mg/L), Corynebacterium spp. (MIC90, 0.12 mg/L), Listeria monocytogenes (MIC90, 0.25 mg/L) and Micrococcus spp. (MIC90, 0.03 mg/L) were very susceptible to dalbavancin. In conclusion, these 2003 baseline resistance surveillance findings confirm the potent dalbavancin activity compared to several comparator agents against important Gram-positive pathogens. This high volume international survey indicates potential therapeutic roles for dalbavancin against many troublesome resistant Gram-positive phenotypes.

Expression of the mef (E) Gene Encoding the Macrolide Efflux Pump Protein Increases in Streptococcus pneumoniae with Increasing Resistance to Macrolides

Active macrolide efflux is a major mechanism of macrolide resistance in Streptococcus pneumoniae in many parts of the world, especially North America. In Canada, this active macrolide efflux in S. pneumoniae is predominantly due to acquisition of the mef(E) gene. In the present study, we assessed the mef(E) gene sequence as well as mef(E) expression in variety of low- and high-level macrolide-resistant, clindamycin-susceptible (M-phenotype) S. pneumoniae isolates (erythromycin MICs, 1 to 32 microg/ml; clindamycin MICs, < or = 0.25 microg/ml). Southern blot hybridization with mef(E) probe and EcoRI digestion and relative real-time reverse transcription-PCR were performed to study the mef(E) gene copy number and expression. Induction of mef(E) expression was analyzed by Etest susceptibility testing pre- and postincubation with subinhibitory concentrations of erythromycin, clarithromycin, azithromycin, telithromycin, and clindamycin. The macrolide efflux gene, mef(E), was shown to be a single-copy gene in all 23 clinical S. pneumoniae isolates tested, and expression post-macrolide induction increased 4-, 6-, 20-, and 200-fold in isolates with increasing macrolide resistance (erythromycin MICs 2, 4, 8, and 32 microg/ml, respectively). Sequencing analysis of the macrolide efflux genetic assembly (mega) revealed that mef(E) had a 16-bp deletion 153 bp upstream of the putative start codon in all 23 isolates. A 119-bp intergenic region between mef(E) and mel was sequenced, and a 99-bp deletion was found in 11 of the 23 M-phenotype S. pneumoniae isolates compared to the published mega sequence. However, the mef(E) gene was fully conserved among both high- and low-level macrolide-resistant isolates. In conclusion, increased expression of mef(E) is associated with higher levels of macrolide resistance in macrolide-resistant S. pneumoniae.

Résistance du streptocoque du groupe A aux macrolides

Penicillin remains the drug of choice for the treatment of Group A Streptococci infections. However, for patients hypersensitive to β-lactam antibiotics and in whom therapy with these drugs fails, macrolides are often the recommended substitute. Over the past few years, increased rates of erythromycin resistance have been reported for Group A Streptococci worldwide. The known mechanisms of macrolide resistance in Streptococci are modification of the ribosomal target by a methylase encoded by erm genes and a macrolide-specific efflux mechanism encoded by the mef(A) gene. Mutation of the ribosomal target of macrolides is a rare resistance mechanism in streptococci. A total of 22.4% in France in 2003 of A Group Streptococcus were erythromycin resistant, and 69.4%, 4.2%, and 26.4% of these isolates harbored ermB, ermA, and mefA, respectively. Increasing resistance in France is mainly associated with a few emm type 28 clones.

Activity of Telithromycin Against Multi-Drug Resistant Streptococcus pneumoniae and Molecular Characterization of Macrolide and Tetracycline Resistance Determinants

The antistreptococcal activity of telithromycin and 11 different comparators was evaluated in 26 multi-drug resistant (MDR) Streptococcus pneumoniae strains collected during 2002-2003 as part of the ongoing PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) Italian Surveillance Program. The strains were characterized for their susceptibility to antibiotics both at the phenotypic and genotypic levels; furthermore, the association of erm(B), mef(A) class and tet(M) genes, as well as the mobile elements carrying them were determined. The strains in this study were resistant to penicillin (MIC ≥2 mg/l) in 23.1% of cases, resistant to tetracycline in 88.4%, to cotrimoxazole in 34.6% and cefuroxime in 26.9% while only telithromycin and levofloxacin retained 100% activity against all microorganisms. Co-existence of different resistance determinants was found in 19.2% of all isolates collected in our laboratory, coming from southern Italy. Twenty-three isolates showing the MLSB phenotype of resistance possessing the erm(B) gene (88.5%), associated with tet(M), were carried on the same Tn1545-like element, while two isolates showing the M phenotype possessing the mef(A) gene alone, were carried on Tn1207.1. In only one strain were mef(E) and tet(M) together carried on Tn2009.

Macrolide Efflux in Streptococcus pneumoniae Is Mediated by a Dual Efflux Pump ( mel and mef ) and Is Erythromycin Inducible

Macrolide resistance in Streptococcus pneumoniae due to efflux has emerged as an important worldwide clinical problem over the past decade. Efflux is mediated by the genes of the genetic element mega (macrolide efflux genetic assembly) and related elements, such as Tn1207.1. These elements contain two adjacent genes, mef (mefE or mefA) and the closely related mel gene (msrA homolog), encoding a proton motive force pump and a putative ATP-binding cassette transporter homolog, and are transcribed as an operon (M. Del Grosso et al., J. Clin. Microbiol. 40:774-778, 2004; K. Gay and D. S. Stephens, J. Infect. Dis. 184:56-65, 2001; and M. Santagati et al., Antimicrob. Agents Chemother. 44:2585-2587, 2000). Previous studies have shown that Mef is required for macrolide resistance in S. pneumoniae; however, the contribution of Mel has not been fully determined. Independent deletions were constructed in mefE and mel in the serotype 14 macrolide-resistant strains GA16638 (erythromycin [Em] MIC, 8 to 16 microg/ml) and GA17719 (Em MIC, 2 to 4 microg/ml), which contain allelic variations in the mega element. The MICs to erythromycin were significantly reduced for the independent deletion mutants of both mefE and mel compared to those of the parent strains and further reduced threefold to fourfold to Em MICs of <0.15 microg/ml with mefE mel double mutants. Using quantitative reverse transcription-PCR, the expression of mefE in the mel deletion mutants was increased more than 10-fold. However, in the mefE deletion mutants, the expression of mel did not differ significantly from the parent strains. The expression of both mefE and mel was inducible by erythromycin. These data indicate a requirement for both Mef and Mel in the novel efflux-mediated macrolide resistance system in S. pneumoniae and other gram-positive bacteria and that the system is inducible by macrolides.

Development of a real-time PCR assay on the Roche Light-Cycler for the detection of erm and mef erythromycin resistance genes in β-haemolytic streptococci

Sir, Although erythromycin resistance in streptococci is predominantly due to target site modification by rRNA methylases (encoded by erm genes) or drug efflux (encoded by mef genes), novel resistance mechanisms continue to emerge. Furthermore, susceptibility to macrolides, lincosamides, streptogramins and ketolides varies depending on the distribution of different erythromycin resistance mechanisms. Therefore, phenotypic and genotypic erythromycin resistance surveillance data are required as an adjunct in determining therapy for streptococcal infections. In the UK, erythromycin resistance in Lancefield group B (GBS), C (GCS) and G (GGS) streptococci is increasing, but data on the molecular basis of resistance are limited. PCR with agarose gel analysis or microwell-format probe hybridization can be used to detect erm and mef genes; however, both require additional handling steps and gel analysis lacks the specificity of sequencing or hybridization analyses. Real-time PCR has the dual benefits of rapid amplification and specific detection, occurring simultaneously in the same tube, reducing the risks of contamination. The aim of this study was to develop a real-time PCR assay to detect both erm and mef genes and characterize erythromycin resistance genes in GBS, GCS and GGS isolated from clinical samples. This approach has not been used before in detecting erm and/or mef genes in streptococci. Positive control strains containing erm and mef genes used were: 02C1064 [Streptococcus pyogenes, mef(A/E)]; 02C1110 [S. pyogenes, erm(A) subclass erm(TR)]; RN1389 [Staphylococcus aureus, erm(A)]; JH2-2 [Enterococcus faecalis, erm(B)] and RN4220 [S. aureus, erm(C)]. Sixty-one erythromycinresistant streptococci (14 GBS, four GCS and 43 GGS) collected from patients with community-acquired infections at two different hospitals during two different 6 month periods were also tested.

Mechanisms of resistance to telithromycin in Streptococcus pneumoniae

Reports of ketolide resistance remain scarce, however, a few laboratory-derived and clinical isolates of resistant Streptococcus pneumoniae have been documented. Mutations in key telithromycin-binding sites such as domains II and V of the 23S rRNA and ribosomal proteins L4 and L22, as well as mutations of the resistance determinant erm(B) are associated with elevated telithromycin MICs. Mutations in the secondary binding site of domain II coupled with ribosomal methylation may have serious resistance consequences should the domain II binding site be lost. Although ketolides are purported to maintain excellent activity against efflux-positive isolates, laboratory-derived telithromycin-resistant strains have been generated. As telithromycin usage increases, ketolide-resistant isolates of S. pneumoniae may well increase.

Synthesis, Characterization and In Vitro Antimicrobial Activity of Novel Sulfonylureas of 15-Membered Azalides

Three series of the novel sulfonylurea derivatives of 15-membered azalides, i.e. 9a-N-[N'-(aryl)sulfonylcarbamoyl] (4a-4f, 5a-5f), 9a-N-{N'-[(aryl)sulfonylcarbamoyl-gamma-aminopropyl]} (10a-10f, 11a, 11c) and 9a-N-{N'-(beta-cyanoethyl)-N'-[(aryl)sulfonylcarabamoyl-gamma-aminopropyl]} (14a-14f, 15a, 15b, 15f) derivatives of 9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A (2) and 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A (3) were prepared and their structures elucidated by NMR and IR spectroscopic methods and mass spectrometry. Minimal inhibitory concentration (MIC) of these compounds was determined on a panel of sensitive and resistant Gram-positive and Gram-negative bacterial strains. Several compounds of the series of 9a-N-[N'-(aryl)sulfonylcarbamoyl] derivatives that showed significant improvements in activity against inducible resistant Streptococcus pyogenes strain were suggested for further optimization.

An Emptying Quiver: Antimicrobial Drugs and Resistance

An Emptying Quiver: Antimicrobial Drugs and Resistance

Fluoroquinolones demonstrate in vitro activity against multi-drug resistant Streptococcus pneumoniae (MDRSP),

Fluoroquinolones demonstrate in vitro activity against multi-drug resistant Streptococcus pneumoniae (MDRSP),

Antibiotic resistant Streptococcus pneumoniae and hemolytic uremic syndrome

The hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in young children and most often follows an episode of gastroenteritis caused by an enterohemorrhagic strain of Escherichia coli (O157:H7). HUS induced by Streptococcus pneumoniae (SP) is rare. We report an 18-month-old patient who presented with HUS associated with SP resistant to penicillin and cephalosporins. Despite a protracted course including renal failure requiring 15 days of peritoneal dialysis, her kidney function completely recovered.

Streptococcus sanguinis Endocarditis in a Patient Who Received Clindamycin for Dental Prophylaxis

Antibiotic prophylaxis has been recommended to prevent infective endocarditis in patients with valvular heart disease undergoing dental procedure. Erythromycin and clindamycin have been recommended as alternative agents in those who are allergic to penicillin. We report a penicillin-allergic patient who developed infective endocarditis despite clindamycin prophylaxis. Viridans-group Streptococcus that was later identified as Streptococcus sanguinis resistant to clindamycin was isolated from her blood. Initial therapy with clindamycin did not improve her symptoms. Her symptoms responded to linezolid therapy. She underwent mitral valve replacement because of deteriorating cardiac function. Postoperatively, she was treated successfully with linezolid and levofloxacin intravenously for 4 weeks. She remained well on her 30-month follow-up. Viridans-group Streptococcus, as a group, has been shown to be increasingly resistant to various antimicrobial agents including clindamycin and erythromycin. Although the percentage of resistant viridans-group Streptococcus strains is still low in most areas, local resistance should be monitored. If this trend should continue, the value of these antibiotics as prophylactic agent should be reevaluated.

High nasopharyngeal carriage of drug resistant Streptococcus pneumoniae and Haemophilus influenzae in North Indian schoolchildren

To determine the carriage rate of Streptococcus pneumoniae and Haemophilus influenzae in healthy Indian schoolchildren. The prevalence of antibiotic resistant strains in the community may be used to assess the trends of antibiotic resistance in invasive strains. Prevalence of resistance to various antimicrobial drugs among S. pneumoniae and H. influenzae was estimated. Two thousand four hundred subjects, aged 5-10 years, were enrolled from 45 rural and 45 urban schools. A nasopharyngeal swab was collected from each child, after taking informed written consent. Swabs were processed to isolate S. pneumoniae and H. influenzae. All isolates were tested for resistance to chloramphenicol, erythromycin and co-trimoxazole. Streptococcus pneumoniae isolates were also tested against tetracycline and oxacillin while H. influenzae isolates were tested against ampicillin. Nasopharyngeal carriage of S. pneumoniae and H. influenzae was high in healthy schoolchildren. Stratified analysis showed that nasal carriage of pneumococci in urban children was significantly lower than in rural children [46.8% vs. 53.2%, P<0.001]. Carriage rates of H. influenzae in male and female populations were significantly different (47.8% vs. 52.3%, P<0.04). Penicillin resistance in S. pneumoniae was found low (3.3%), but 22.9% of H. influenzae isolates were ampicillin resistant. Resistance to co-trimoxazole was very high in both S. pneumoniae (81.8%) and H. influenzae (67.3%). There is high nasopharyngeal carriage of drug resistant S. pneumoniae and H. influenzae in schoolchildren of north India. Currently, in India, co-trimoxazole for 5 days is recommended for treatment of non-severe pneumonia and third generation cephalosporins are drug of choice for management of severe pneumococcal/H. influenzae diseases. We found high co-trimoxazole resistance and low penicillin resistance in pneumococcal isolates. This justifies empirical use of penicillin in management of invasive pneumococcal infections in India.

Tigecycline: clinical evidence and formulary positioning

Tigecycline, is a novel broad-spectrum glycylcycline antibiotic, which has activity against a broad range of Gram-positive, Gram-negative, atypical, anaerobic and antibiotic-resistant bacteria. This includes activity against MRSA, VRE and penicillin resistant Streptococcus pneumoniae. Whilst exhibiting antibacterial activities typical of earlier tetracyclines, it has more potent activity against tetracycline-resistant organisms. Although a bacteriostatic compound in vitro, its effectiveness in clinical trials suggests that traditional laboratory thinking about using bacteriostatic drugs in serious infections needs to be revised. Unlike existing tetracyclines, tigecycline is only available as an intravenous preparation, is administered twice daily although its long half life and post-antibiotic effect may make once daily dosing possible, appears to have good tissue penetration (e.g. skin) and requires no adjustment in the presence of renal or hepatic diseases. It is efficacious in complicated skin and soft tissue infections and in intra-abdominal infections. In three trials, it was well tolerated despite increased frequency of nausea and vomiting. In the light of these early clinical data and the likelihood that this agent will become available for clinical use within the next 12–24 months, this review aims to summarise the key clinical data and potential formulary considerations for the future use of this agent, subject to further clinical trials and publication of clinical human data.

Streptococcal toxic shock syndrome by an iMLS resistant M type 77 Streptococcus pyogenes in the Netherlands

An increasing number of group A streptococci (GAS) with constitutive or inducible resistance to macrolide-lincosamide-streptogramin B antibiotics (cMLS or iMLS phenotype) is observed in Europe, but MLS resistant GAS associated with streptococcal toxic shock syndrome (STSS) has not been reported. We describe a patient admitted with STSS caused by an iMLS resistant T28 M77 Streptococcus pyogenes carrying the ermA [subclass TR] gene. A 2-y retrospective analysis among 701 nationwide collected GAS strains revealed an incidence of 3.1% of this M type 77 GAS. Analysis of 17 available M77 strains (12 T28 and 5 T13) indicated that 2 (12%) were MLS resistant due to the ermA [TR] gene. Both MLS resistant strains were cultured from blood and belonged to T28 serotype. Multilocus sequence typing (MLST) showed that all M77 isolates belonged to sequence type 63. We conclude that 17 M77 GAS collected in the Netherlands in a 2-y period were associated with invasive disease and belonged to the same clonal complex. Since only 12% carried the ermA [TR] resistance gene, it is very likely that the gene has been acquired by horizontal transmission rather than from spread of a resistant circulating clone.