Prevalence of phenotypic resistance of Staphylococcus aureus isolates to macrolide,lincosamide, streptogramin B,ketolid and linezolid antibiotics in Turkey

The incidence of drug-resistant pathogens differs greatly between countries according to differences in the usage of antibiotics. The purpose of this study was to investigate the phenotypic resistance of 321 methicillin resistance Staphylococcus aureus (MRSA) and 195 methicillin susceptible S. aureus (MSSA) in a total of 516 S. aureus strains to macrolide, lincosamide, streptogramin B (MLS_B), ketolid, and linezolid. Disk diffusion method was applied to determine MLS_B phenotype and susceptibility to different antibiotic agents. It was found that 54.6% of the isolates were resistant to erythromycin (ERSA), 48% to clindamycin, 55% to azithromycin, 58.7% to spiramycin, 34.7% to telithromycin, and 0.4% to quinupristin-dalfopristin, respectively. No strain resistant to linezolid was found. The prevalence of constitutive (cMLS_B), inducible (IMLS_B), and macrolides and type B streptogramins (M/MS_B) among ERSA isolates (237 MRSA, 45 MSSA) was 69.6%, 18.2%, and 12.2% in MRSA and 28.9%, 40%, and 31.1% in MSSA, respectively. In conclusions, the prevalence of cMLS_B was predominant in MRSA; while in MSSA strains, iMLS_B and M/MS_B phenotype were more higher than cMLS_B phenotype resistance. The resistance to quinupristindalfopristin was very low, and linezolid was considered as the most effective antibiotic against all S.aureus strains.     

The use of macrolides in treatment of upper respiratory tract infections

Antimicrobial resistance is a growing problem among upper respiratory tract pathogens. Resistance to β-lactam drugs among Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus pyogenes is increasing. As safe and well-tolerated antibiotics, macrolides play a key role in the treatment of community-acquired upper respiratory tract infections (RTIs). Their broad spectrum of activity against gram-positive cocci, such as S. pneumoniae and S. pyogenes, atypical pathogens, H. influenzae (azithromycin and clarithromycin), and Moraxella catarrhalis, has led to the widespread use of macrolides for empiric treatment of upper RTIs and as alternatives for patients allergic to β-lactams. Macrolide resistance is increasing among pneumococci and recently among S. pyogenes, and is associated with increasing use of the newer macrolides, such as azithromycin. Ribosomal target modification mediated by erm(A) [erm(TR)] and erm(B) genes and active efflux due to mef(A) and mef(E) are the principal mechanisms of resistance in S. pneumoniae and S. pyogenes. Recently, ribosomal protein and RNA mutations have been found responsible for acquired resistance to macrolides in S. pneumoniae, S. pyogenes, and H. influenzae. Although macrolides are only weakly active against macrolide-resistant streptococci species producing an efflux pump (mef) and are inactive against pathogens with ribosomal target modification (erm), treatment failures are uncommon. Therefore, macrolide therapy, for now, remains a good alternative for treatment of upper RTIs; however, continuous monitoring of the local resistance patterns is essential.     

The use of macrolides in treatment of upper respiratory tract infections

Antimicrobial resistance is a growing problem among upper respiratory tract pathogens. Resistance to β-lactam drugs among Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus pyogenes is increasing. As safe and well-tolerated antibiotics, macrolides play a key role in the treatment of community-acquired upper respiratory tract infections (RTIs). Their broad spectrum of activity against gram-positive cocci, such as S. pneumoniae and S. pyogenes, atypical pathogens, H. influenzae (azithromycin and clarithromycin), and Moraxella catarrhalis, has led to the widespread use of macrolides for empiric treatment of upper RTIs and as alternatives for patients allergic to β-lactams. Macrolide resistance is increasing among pneumococci and recently among S. pyogenes, and is associated with increasing use of the newer macrolides, such as azithromycin. Ribosomal target modification mediated by erm(A) [erm(TR)] and erm(B) genes and active efflux due to mef(A) and mef(E) are the principal mechanisms of resistance in both S. pneumoniae and S. pyogenes. Recently, ribosomal protein and RNA mutations have been found to be responsible for acquired resistance to macrolides in S. pneumoniae, S. pyogenes, and H. influenzae. Although macrolides are only weakly active against macrolide-resistant streptococci species, producing an efflux pump (mef), and are inactive against pathogens with ribosomal target modification (erm), treatment failures are uncommon. Therefore, macrolide therapy, for now, remains a good alternative for treatment of upper RTIs; however, continuous monitoring of the local resistance patterns is essential.     

Correlation between usage of macrolide antibiotic and resistance of Streptococcus pneumoniae clinic isolates from chongqing children's hospital

To investigate the reasons of growing resistance problem of Streptococcus pneumoniae against macrolide in Chongqing, a retrospective method was employed to measure the minimal inhibition concentrations (MIC) of macrolide antibiotic against 1,210 S. pneumoniae clinic isolates. The defined daily doses (DDDs) of macrolide antibiotic were calculated. Polymerase chain reaction (PCR) was used to determine the presence of the erythromycin‐resistant genes in 100 macrolide‐resistant S. pneumoniae isolates. A decrease in macrolide consumption, from 371,100 DDDs in 2002 to 182,500 DDDs in 2005 (51% reduction); however, the rate of erythromycin resistance in S. pneumoniae showed continued increase from 88.0% in 2002 to 96.0% in 2005. No linear correlation was observed between the decline in macrolide consumption and continued increase in resistant rate in S. pneumoniae. In 100 macrolide‐resistant S. pneumoniae isolates, 68 had both erm(B) and mef(A) genotypes, 10 only had the erm(B), 20 only had the mef(A). Co‐existences of ribosomal modification coded by erm(B) gene and efflux effects coded by mef(A) gene were the main resistance mechanism against macrolides and might be attributed to the high drug resistance of S. pneumoniae in Chongqing. Pediatr Pulmonol. 2009; 44:917–921. © 2009 Wiley‐Liss, Inc.     

Distribution of erm genes and low prevalence of inducible resistance to clindamycin among staphylococci isolates

IntroductionResistance to macrolides, lincosamides and streptogramins B (MLS_B antibiotics) in staphylococci may be due to modification in ribosomal target methylase encoded by erm genes. The expression of MLS_B resistance lead to three phenotypes, namely constitutive resistance (cMLS_B), inducible resistance (iMLS_B), and resistance only to macrolides and streptogramins B (MS_B). The iMLS_B resistance is the most difficult to detect in the clinical laboratory.ObjectiveThis study investigated the expression of MLS_B resistance and the prevalence of the erm genes among 152 clinical isolates of Staphylococcus aureus and coagulase-negative Staphylococcus (CNS) from Hospital de Clínicas de Porto Alegre.MethodsPrimary MLS_B resistance was detected by the disk diffusion method. Isolates with iMLS_B phenotype were tested by double-disk induction method. All isolates were tested by a genotypic assay, PCR with specific primers.ResultsA total of 46.7% of staphylococci were positive for cMLS_B; 3.3% for iMLS_B and 3.3% for MS_B. One or more erm genes were present in 50.1% of isolates. The gene ermA was detected in 49 isolates, ermC in 29 and ermB in 3.ConclusionThe prevalence of the ermA, ermB and ermC genes were 29.6%, 17.1% and 0.66% respectively, and constitutive resistance was the most frequent as compared to the other two phenotypes.     

The use of ketolides in treatment of upper respiratory tract infections

Recent surveillance studies suggest that the incidence of resistance to macrolide antibiotics in common communityacquired respiratory tract pathogens, particularly Streptococcus pneumoniae and Streptococcus pyogenes, is increasing and limiting the usefulness of these drugs. The ketolides, of which telithromycin is the first to be available for clinical use (but not yet in the United States), represent a new class of antibacterials developed specifically to combat respiratory tract pathogens that have acquired resistance to macrolides. The ketolides possess innovative structural modifications, a 3-keto group and a large N-substituted C11, C12-carbamate side chain. This novel structure allows ketolides, which are inhibitors of protein synthesis, to exert a more effective interaction with domain II of the 23S rRNA, enhancing binding to bacterial ribosomes and allowing binding to macrolide-lincosamidestreptogramin B-resistant ribosomes. This novel chemical structure also promotes greater stability of telithromycin in acid conditions, providing the potential for greater stability in gastric fluid and at cellular/tissue levels. Early clinical trials support the bacteriologic and clinical efficacy of telithromycin in the treatment of upper respiratory tract infections (RTIs) such as streptococcal pharyngitis and acute sinusitis, including infections caused by macrolide-resistant S. pneumoniae and S. pyogenes. Common adverse side effects associated with telithromycin are predominantly gastrointestinal, usually of mild to moderate severity, and rarely involve withdrawal of the drug. Telithromycin represents an attractive option for the empiric treatment of upper RTIs, especially as resistance to macrolides is likely to continue to increase.     

What is the clinical impact of macrolide resistance?

Respiratory tract infections are treated empirically. Treatment is based on the likely pathogens and their antibiotic susceptibility. The most common respiratory tract pathogen is Streptococcus pneumoniae. In the United States, approximately 25% to 30% of S. pneumoniae are resistant to erythromycin and other macrolides. There are two mechanisms of resistance: ribosomal methylation that causes high-level resistance, and an efflux pump that causes low-level resistance. Macrolides are ineffective in animal models that use pneumococcal isolates with the methylase- or efflux-mediated resistance mechanisms. There are many case reports that describe clinical failure and isolation of a macrolide-resistant pneumococcus while a patient receives macrolide treatment. Two recent studies that included macrolide-susceptible and macrolideresistant pneumococci showed that breakthrough bacteremia in patients receiving macrolide treatment occurred only with macrolide-resistant isolates. Study of bacteremic disease ensures the pathogenic role of the pneumococcus; however, it underestimates the true clinical impact of macrolide resistance.     

Susceptibility of bacterial isolates from community-acquired infections in sub-Saharan Africa and Asia to macrolide antibiotics

Objective To review the literature on the susceptibility of common community pathogens in sub‐Saharan Africa and Asia to the macrolide antibiotics. Methods Inclusion criteria required that isolates were collected since 2004 to ensure results were of contemporary relevance. The data were aggregated by region, age group and sterility of site of culture sample. Results A total of 51 studies were identified, which reported the macrolide antimicrobial susceptibilities of common bacterial pathogens isolated since 2004. In general, there was less macrolide resistance in African than in Asian isolates. Most African studies reported high levels of macrolide susceptibility in Streptococcus pneumoniae, whereas most Chinese studies reported high levels of resistance. There was very little information available for Gram‐negative organisms. Conclusions Susceptibility of the pneumococcus to macrolides in SSA remains high in many areas, and good activity of azithromycin has been shown against Salmonellae spp. in Asia. In urban areas where high antibiotic consumption is prevalent, there was evidence of increased resistance to macrolides. However, there is no information on susceptibility from large areas in both continents.     

Clinical efficacy of macrolide antibiotics against genetically determined macrolide-resistant Mycoplasma pneumoniae pneumonia in paediatric patients

Background and objective: Since 2000, the prevalence of macrolide‐resistant (MR) Mycoplasma pneumoniae has increased among paediatric patients in Japan. To determine the efficacy of macrolides against MR M. pneumoniae pneumonia, microbiological and clinical efficacies were compared during the antibiotic treatment. Methods: Samples from a total of 30 children with M. pneumoniae pneumonia, as confirmed by PCR and serology, were analyzed. Primers for domain V of 23S rRNA were used, and DNA sequences of the PCR products were compared with the sequence of an M. pneumoniae reference strain. Results: Isolates from 21 patients demonstrated point mutations, and these patients were defined as MR. The remaining nine patients, whose isolates showed no point mutations, were categorized as control (macrolide‐sensitive) patients. The number of M. pneumoniae in nasopharyngeal samples from the control group decreased rapidly 48 h after initiation of macrolide treatment and showed a close relationship with clinical outcome. In contrast, the number of M. pneumoniae 48 h after initiation of macrolide treatment were significantly higher in samples from MR patients than in samples from macrolide‐sensitive patients. In 15 of 21 MR patients, fever persisted for more than 48 h after the initiation of macrolide treatment. When treatment was changed to minocycline, fever disappeared within 48 h in all these MR patients. There were no differences between MR patients who demonstrated a reduction in fever and those in whom fever persisted after 48 h of macrolide treatment. Conclusions: The microbiological and clinical efficacies of macrolides for treating patients with MR M. pneumoniae pneumonia were low. These results show that macrolides are clearly less effective in patients with MR M. pneumoniae pneumonia.     

Antibiotic Resistance in Sputum Isolates of Streptococcus pneumoniae in Chronic Obstructive Pulmonary Disease is Related to Antibiotic Exposure

ABSTRACT

Streptococcus pneumoniae (S. pneumoniae) is recovered from sputum of patients with chronic obstructive pulmonary disease (COPD) during stable disease and exacerbations. In patients with community acquired pneumonia, antibiotic exposure in the prior 3–6 months is associated with recovery of antibiotic resistant isolates of S. pneumoniae. Whether the same relationship is seen in COPD is not known. From April 1994 to June 2004, 127 adults with COPD were enrolled in a prospective longitudinal study. Sputum isolates of S. pneumoniae were characterized with susceptibility testing and pulsed-field gel electrophoresis (PFGE). The relationship between antibiotic use in the previous 3 and 6 months with either new acquisition of a resistant pneumococcal isolate or development of resistance (4-fold increase in MIC) in a pre-existing colonizing pneumococcal strain was determined. A total of 194 pneumococcal isolates were recovered from 38 patients. Among 71 newly acquired and 4 resistance-emergent strains analyzed further, rates of resistance to penicillin (MIC ≥2), erythromycin (MIC ≥1), tetracycline (MIC ≥8) and trimethoprim/sulfamethoxazole (MIC ≥4) were 8%, 24%, 17% and 16% respectively. Flouroquinolone resistance was not seen. Among strains isolated from patients exposed to a macrolide within 6 months, 53.6% displayed erythromycin resistance vs. 14% of strains without such exposure (p = 0.00085). Similar associations were not seen for other antibiotics. Macrolide use in the previous 6 months is associated with macrolide resistance in sputum isolates of S. pneumoniae. Recent antibiotic exposure may help in determining appropriate antibiotic treatment in these patients.     

Detección fenotípica de mecanismos de resistencia en microorganismos grampositivos

Antimicrobial resistance mechanisms among clinically relevant gram-positive microorganisms can be demonstrated using phenotypic tests that enable the interpretation of underlying mechanisms responsible for the in vitro resistance. The reporting of these mechanisms, either inferred or demonstrated, helps in the adjustment of clinical treatments and the epidemiological follow up of resistance traits. In the present work, phenotypic tests for detection of antimicrobial resistance mechanisms involving the most frequent antimicrobial families used against Staphylococcus spp., Enterococcus spp. and Streptococcus pneumoniae are analysed. In the case of Staphylococcus, phenotypic tests to reveal the mechanisms of resistance against beta-lactams, macrolides, lincosamides and streptogramin B (MLS_B), as well as intermediate susceptibility to glycopeptides, resistance to aminoglycosides, mupirocin and linezolid are reviewed. Tests to detect glycopeptide resistance and high-level aminoglycoside resistance among enterococci are analysed. Detection of penicillin resistance, as well as diminished susceptibility to third generation cephalosporins, together with diminished susceptibility or even resistance to fluoroquinolones is also detailed.     

突变敏感性分子开关检测肺炎支原体对大环内酯类抗生素的耐药性研究

目的 应用突变敏感性分子开关检测肺炎支原体对大环内酯类抗生素的耐药性。方法 采用微量稀释法检测5种常用大环内酯类抗生素对40株Mp临床分离株的药物敏感性;建立高保真聚合酶和3'硫化修饰引物的分子开关,用分子开关进行Mp临床分离株的PCR扩增,检测其是否存在Mp 23S rRNA 2063、2064和2617 3个热点突变,并通过基因测序进一步确定是否存在点突变,分析点突变与大环内酯类抗生素敏感性之间的关系。结果 5种大环内酯类抗生素中,Mp对14元环的红霉素和克拉霉素耐药程度最高,其MIC≥128 mg/L;对15元环的大环内酯类抗生素阿奇霉素和交沙霉素相对敏感,其中交沙霉素抗Mp活性最高,其MIC≤4 mg/L。用高保真聚合酶和3'硫化修饰引物的分子开关行PCR扩增,检测出35株发生了2063位点基因突变,3株发生2064位点基因突变,未检测出2617位点突变。用基因测序检测到35株Mp发生A2063G的突变,3株发生A2064G的突变,未检测到2617位点突变,与分子开关的检测结果一致,并且2063、2064位点突变Mp株均对大环内酯类药物高度耐药。结论 分子开关可识别23S rRNA基因突变,可用于分析Mp对大环内酯类抗生素的敏感性。     

PROTEKT 1999-2000: a multicentre study of the antimicrobial susceptibility of respiratory tract pathogens in Japan.

DESIGN: A six-centre study in Japan during the winter of 1999-2000 assessed the in vitro activity of >20 antimicrobial agents against the common respiratory pathogens Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis. The minimum inhibitory concentrations (MIC) of each antimicrobial was determined against these isolates using National Committee for Clinical Laboratory Standards (NCCLS) methodology. RESULTS: Among S. pneumoniae isolates, 44.5% were penicillin resistant. The macrolide resistance rate was 77.9% with 90.5% of penicillin-resistant strains also being macrolide resistant. Resistance mechanisms in macrolide-resistant isolates were identified as mef(A) or erm(B) in 42.5% and 52.5%, respectively. Of the fluoroquinolone-resistant isolates (1.3%), most were also penicillin and macrolide resistant. All strains were inhibited by telithromycin at 相似文献   

Epidemiology and clinical manifestations of children with macrolide‐resistant Mycoplasma pneumoniae pneumonia in Taiwan

Mycoplasma pneumoniae accounts for 10–30% of community‐acquired pneumonia (CAP) in children. This study reveals the epidemiology and clinical manifestations of children with macrolide‐resistant (ML^r) M. pneumoniae pneumonia in Taiwan. Respiratory tract specimens were collected from children hospitalized with CAP for evaluation via PCR followed by DNA sequencing for several point mutations related to the ML^r character. Of the 412 specimens collected during the study period, 60 (15%) were positive for M. pneumoniae, 14 (23%) of which presented point mutation (all A2063G) in 23S rRNA. Clinical symptoms and chest X‐ray findings between the ML^s and ML^r groups were not significantly different. However, the ML^r group had longer mean duration of fever after azithromycin treatment (3.2 days vs. 1.6 days, P = 0.02) and significantly higher percentage of changing antibiotics for suspected ML^r strain (42% vs. 13%, P = 0.04). Although 58% of children in the ML^r group did not receive effective antibiotics, all children were discharged without sequelae. In conclusion, 15% of CAP in children is caused by M. pneumoniae and the macrolide‐resistance rate is 23% in Taiwan. Despite ineffective antibiotics, children with ML^r M. pneumoniae pneumonia recover completely. Pediatr Pulmonol. 2013; 48:904–911. © 2012 Wiley Periodicals, Inc.     

Erythromycin Resistance in Streptococcus pyogenes and Macrolide Consumption in a Central Italian Region

Background:   

The study investigated macrolide resistance in Streptococcus pyogenes in a central Italian area from 2001 to 2006 and the possible correlation between antibiotic consumption and fluctuations of resistance percentages.     

Failure of levofloxacin treatment in community-acquired pneumococcal pneumonia

Background  

Streptococcus pneumoniae is the leading cause of community-acquired pneumonia (CAP). High global incidence of macrolide and penicillin resistance has been reported, whereas fluoroquinolone resistance is uncommon. Current guidelines for suspected CAP in patients with co-morbidity factors and recent antibiotic therapy recommend initial empiric therapy using one fluoroquinolone or one macrolide associated to other drugs (amoxicillin, amoxicillin/clavulanate, broad-spectrum cephalosporins). Resistance to fluoroquinolones is determined by efflux mechanisms and/or mutations in the parC and parE genes coding for topoisomerase IV and/or gyrA and gyrB genes coding for DNA gyrase. No clinical cases due to fluoroquinolone-resistant S. pneumoniae strains have been yet reported from Italy.     

肺炎链球菌耐药性检测及其对大环内酯类抗生素耐药机制的研究

目的了解浙江地区肺炎链球菌临床菌株对临床常用抗生素耐药性以及肺炎链球菌对大环内酯类抗生素耐药机制。方法从浙江省不同地区病人临床标本中分离并鉴定肺炎链球菌138株。采用K-B纸片法和E-test检测上述肺炎链球菌临床菌株对9种抗生素的敏感性。采用PCR检测上述菌株中与大环内酯类抗生素耐药性密切相关的ermB和mefE基因携带情况。分析ermB和mefE基因携带、分布状况与红霉素耐药性关系。结果138株肺炎链球菌临床菌株中,对红霉素耐药率高达93.5%(129/138),对头孢噻肟、头孢呋辛、阿莫西林和左氧氟沙星的耐药率较低(2.9%~4.3%)。上述菌株er-mB基因检测阳性率(91.3%,126/138)明显高于mefE基因(33.3%,46/138)(P0.05),其中27.5%菌株(38/138)同时携带。不携带ermB和mefE基因菌株均对红霉素敏感,仅携带mefE基因菌株对红霉素耐药率(62.5%)明显低于同时携带两种基因菌株耐药率(100%)及仅携带ermB基因菌株耐药率(97.7%)(P0.05)。结论红霉素已不适合作为治疗肺炎链球菌感染性疾病的药物。ermB基因是肺炎链球菌临床菌株携带的红霉素耐药相关优势基因。ermB基因可使肺炎链球菌产生较mefE基因更强的红霉素耐药性。     

Drug-resistant <Emphasis Type="Italic">Streptococcus pneumoniae</Emphasis> in community-acquired pneumonia

The emergence of Streptococcus pneumoniae isolates resistant to not only penicillin, but to other antipneumococcal agents as well, has major public health implications. Drug-resistant S. pneumoniae are distributed worldwide, and resistance has become increasingly prevalent in the United States within the past decade. The relevance of resistance, particularly to the β-lactams, to treatment outcome has been subject to debate. Pneumonia due to intermediate-level-resistant penicillinresistant isolates of S. pneumoniae appears to be adequately treated by β-lactam agents. Interpretation of resistance reports, which may be based on achievable cerebrospinal fluid levels of drug, may depend on the clinical setting, and efforts are underway to adjust breakpoints so that reports are more easily applicable to clinical practice. Infectious Diseases Society of America and American Thoracic Society guidelines, as well as others, for community-acquired pneumonia have addressed the impact of drug-resistant S. pneumoniae on antimicrobial selection.     

Spread of a highly mucoid <Emphasis Type="Italic">Streptococcus pyogenes emm</Emphasis>3/ST15 clone

Background  

Hyaluronic acid capsule plays a key role in Streptococcus pyogenes virulence. Circulation of mucoid or highly encapsulated strains has been related to rheumatic fever epidemics and invasive disease in several countries. In 2009, an outbreak of mucoid S. pyogenes isolates was detected in northern Spain. The aim of the study was to describe clinical and molecular characteristics of mucoid strains causing this outbreak and to compare them with a sample of non-mucoid S. pyogenes isolates obtained during the same period of time.