In vitro activity of ertapenem: review of recent studies

Ertapenem is a long-acting, 1beta-methyl parenteral Group 1 carbapenem antibiotic that has a broad antibacterial spectrum and once-a-day dosing supported by clinical studies. Ertapenem is active against both Gram-positive and Gram-negative bacteria, including Enterobacteriaceae, Streptococcus pneumoniae and most species of anaerobic bacteria. Isolates from a variety of infections (intra-abdominal infections, skin/soft-tissue infections, community-acquired pneumonia, pelvic infections and urinary tract infections) are inhibited by ertapenem. It has restricted activity against nosocomial pathogens such as Pseudomonas aeruginosa, Acinetobacter species, methicillin-resistant staphylococci and enterococci. Ertapenem has potent activity against the majority of anaerobic isolates from intra-abdominal infections, and against most of the aerobes isolated from these infections, with the exceptions of the nosocomial pathogens mentioned above. MIC(90)s for most species of Enterobacteriaceae were <1 mg/L, significantly lower than those of imipenem. MIC(90)s for most Bacteroides fragilis group isolates ranged from 1 to 4 mg/L, and MIC(90)s were species specific for Clostridium, ranging from 0.06 mg/L for Clostridium perfringens to 4 mg/L for Clostridium clostridioforme. Ertapenem was equivalent to or better than piperacillin-tazobactam in activity against most anaerobic species isolated from these infections, and was more potent than piperacillin-tazobactam and ceftriaxone against the most common skin pathogens (e.g. methicillin-susceptible Staphylococcus aureus). Ertapenem was highly active against most of the pathogens isolated from patients with community-acquired pneumonia, except for isolates of methicillin-resistant S. aureus (which are infrequent causes of community-acquired infection); these isolates were also resistant to ceftriaxone. Resistance to ertapenem is most commonly attributable to a variety of mechanisms including alterations in penicillin-binding proteins in Gram-positive organisms, and combinations of potent metallo-beta-lactamase enzymes, porin protein defects and efflux pumps in Gram-negative organisms.     

Antibiotic susceptibility of bacterial strains isolated from urinary tract infections in Poland

Worldwide data show that there is increasing resistance among urinary tract pathogens to conventional drugs. The aim of this study was to obtain data on susceptibility patterns of pathogens responsible for urinary tract infections (UTIs) in Poland to currently used antimicrobial agents. A multicentre study of 141 pathogens from hospital-acquired infections and 460 pathogens from community-acquired infections was carried out between July 1998 and May 1999. The most prevalent aetiological agent was Escherichia coli (73.0%), followed by Proteus spp. (8.9%) and other species of Enterobacteriaceae (9.6%). Few community infections were caused by Gram-positive bacteria (2.2%). Gram-positive cocci were isolated more frequently from a hospital setting (14.1%) and the most common were Enterococcus spp. (8.5%). Pseudomonas aeruginosa was found only among hospital isolates and was responsible for 10.7% of infections. E. coli isolates from both community and hospital infections were highly susceptible to many antimicrobial agents with the exception of those isolates producing extended-spectrum beta-lactamases (ESBLs). Of all Enterobacteriaceae tested, 38 strains (6.9%) were capable of producing ESBLs.     

The molecular mechanisms of resistance to B-lactams of pathogens of hospital-acquired infections

The data of local microbiologic monitoring was used to study the profiles and mechanisms of resistance to beta-lactams antibiotics of gram-negative isolates of bacteria, pathogens of hospital-acquired infections in hospital reanimation and surgical departments. The study included 210 clinical isolates of pathogens of hospital-acquired infections: Pseudomonas aeruginosa--86 (40.9%), Acinetobacter baumannii--45 (21.4%), Klebsiella pneumoniae--52 (24.8%), Escherichia coli-23 (11.0%), Enterobacter spp.--4 (1.9%). The profiles of resistance to antibiotics were analyzed using the technique of serial micro-dilutions. The detection of the most common and clinically significant gens of beta-lactamases of gram-negative bacteria was implemented using the PCR technique and sequence analysis. The most activity was detected among carbapenems and cephaperazone/sulbactam. The local characteristics of prevalence of gens coding beta-lactamases (TEM, SHV, CTX) in K. pneumoniae and E. coli were established The study detected 11 isolates of P aeruginosa resistant to carbapenems and having genetic determinants of VIM-group and coding metal-beta-lactamases. The discussed data permits to assess the indicators of resistance to beta-lactams antibiotics and basic mechanisms of resistance of causative agents of hospital-acquired infections. The studies of this kind are unique for every type of hospital-acquired infection. The results can be used in the development of the concept of etiotropic and empiric therapy.     

Antibacterial Activity of Eravacycline (TP-434), a Novel Fluorocycline,against Hospital and Community Pathogens

Eravacycline (TP-434 or 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline) is a novel fluorocycline that was evaluated for antimicrobial activity against panels of recently isolated aerobic and anaerobic Gram-negative and Gram-positive bacteria. Eravacycline showed potent broad-spectrum activity against 90% of the isolates (MIC₉₀) in each panel at concentrations ranging from ≤0.008 to 2 μg/ml for all species panels except those of Pseudomonas aeruginosa and Burkholderia cenocepacia (MIC₉₀ values of 32 μg/ml for both organisms). The antibacterial activity of eravacycline was minimally affected by expression of tetracycline-specific efflux and ribosomal protection mechanisms in clinical isolates. Furthermore, eravacycline was active against multidrug-resistant bacteria, including those expressing extended-spectrum β-lactamases and mechanisms conferring resistance to other classes of antibiotics, including carbapenem resistance. Eravacycline has the potential to be a promising new intravenous (i.v.)/oral antibiotic for the empirical treatment of complicated hospital/health care infections and moderate-to-severe community-acquired infections.     

Efficacy of linezolid versus comparator therapies in Gram-positive infections

Treatment of Gram-positive bacterial infections is currently a therapeutic challenge because many of these pathogens are now resistant to standard antimicrobial agents. The emergence of multidrug-resistant, Gram-positive pathogens emphasizes the need for new antimicrobial therapy. Linezolid is an oxazolidinone antibiotic with a novel mechanism of action that works by inhibiting bacterial protein synthesis by blocking formation of the initiation complex. It is active against Gram-positive organisms resistant to other antibiotics, including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant enterococci (VRE). Results are encouraging from several large-scale, randomized, Phase III trials comparing the efficacy and safety of linezolid with standard comparator agents for the treatment of nosocomial pneumonia, community-acquired pneumonia, skin and skin structure infections, and infections due to MRSA and VRE. Intravenous/oral linezolid is a promising antimicrobial agent and provides the clinician with an additional treatment option, particularly among the limited therapies for resistant Gram-positive bacterial infections.     

In vitro activity of MK-0366 against clinical urinary pathogens including gentamicin-resistant Pseudomonas aeruginosa.

MK-0366, a new derivative of nalidixic acid, was tested against 250 urinary pathogens including Escherichia coli, Serratia marcescens, and Pseudomonas aeruginosa. This new agent was more active than any of the other antibiotics tested, which included carbenicillin, ampicillin, cephalexin, tetracycline, trimethoprim, trimethoprim-sulfamethoxazole, and nalidixic acid. Gentamicin-resistant P. aeruginosa were highly sensitive to MK-0366, with a 90% minimal inhibitory concentration of 0.8 microgram/ml. Serratia strains were the most resistant organisms, with a 90% minimal inhibitory concentration of 3.1 micrograms/ml. These results suggest that clinical trials should be designed to investigate the clinical usefulness of this new drug in urinary infections.     

Ceftazidime in serious hospital-acquired infections

Thirty-four patients, most of them immunocompromised, with severe hospital-acquired infections, including septicaemia, respiratory tract and complicated urinary tract infections were treated with ceftazidime 1-2 g intravenously 8-hourly. Twenty-six patients were cured or improved (76%). The most common pathogens were Enterobacteriaceae and Pseudomonas aeruginosa; Gram-positive organisms were isolated from nine patients. Failure were observed in eight patients (24%), four of them had infections caused by resistant organisms, one had infection with Ps. aeruginosa which became resistant during therapy. Superinfection occurred in 11 patients (32%). Mean peak serum levels after 1 g intravenously were 86.2 +/- 30.3 mg/l; after 2 g intravenously 151.6 +/- 52.2 mg/l. The half-life of serum elimination was 1.8-1.9 h, 2 h in patients with liver function disorders and 3 h in patients with renal impairment. Side effects were mild. Ceftazidime is useful in treating Gram-negative infections, but the gaps in its spectrum, the high rate of superinfection and emergence of resistance are matters of concern.     

Nosocomial infections in a respiratory intensive care unit

A total of 250 consecutive admissions to an open-plan respiratory ICU were analyzed prospectively to identify the incidence of secondary hospital-acquired infections and possible predisposing factors. Despite preventative measures and a restricted antibiotic policy, 23.6% of patients developed secondary infections. Patients admitted after multiple trauma were the only diagnostic category of patients who showed a significantly increased incidence of secondary infections. The length of hospitalization and number of patients who had intubations or tracheostomies was higher in the group with secondary infection; the causal relationship was difficult to establish. Patients who were not intubated or tracheostomized did not develop secondary infection. Prior administration of antibiotics did not appear to influence the incidence of secondary infection. There was a significant increase in secondary infections in patients with a higher therapeutic intervention scoring system score. The predominant pathogens cultured were highly resistant Gram-negative organisms, particularly Acinetobacter sp. and Pseudomonas sp. Staphylococcus aureus was the most common Gram-positive pathogen. The ICU course was probably prolonged by the complication of nosocomial infection, which may have contributed to the deaths.     

Comparative in vitro activities of three new quinolones and azithromycin against aerobic pathogens causing respiratory tract and abdominal wound infections

BACKGROUND: In our study the in vitro susceptibility of common pathogens that cause respiratory tract and abdominal wound infections was tested against two newer fluorquinolones (moxifloxacin and gatifloxacin) as well as levofloxacin and azithromycin. METHODS: 50 isolates each of methicillin-susceptible Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa and Haemophilus influenzae isolated from the respiratory tract and from wounds were tested for their susceptibility to moxifloxacin, gatifloxacin, levofloxacin and azithromycin. RESULTS: Moxifloxacin proved to be the most active substance against the tested gram-positive pathogens. Gatifloxacin was the most active against P. aeruginosa. Moxifloxacin and gatifloxacin proved to be comparably active against the clinical isolates of E. coli and H. influenzae. CONCLUSIONS: Moxifloxacin and gatifloxacin display excellent activity against respiratory pathogens as well as nosocomial pathogens causing abdominal wound infections. When treating infections caused by P. aeruginosa the earlier fluorquinolones such as ciprofloxacin or ofloxacin are the substances of choice.     

Comparative in vitro activities of beta-lactam-tobramycin combinations against Pseudomonas aeruginosa and multidrug-resistant gram-negative enteric bacilli.

Piperacillin was more consistently active than tobramycin, carbenicillin, moxalactam, or ceftriaxone against strains of Pseudomonas aeruginosa isolated from blood cultures and against multidrug-resistant strains. Moxalactam and ceftriaxone were more consistently active than tobramycin, carbenicillin, or piperacillin against multidrug-resistant Enterobacteriaceae. Synergy between beta-lactam antibiotics and tobramycin was frequently observed against strains of P. aeruginosa isolated from blood cultures but not against multidrug-resistant organisms. Piperacillin plus tobramycin was the most active antibiotic combination against P. aeruginosa. Moxalactam plus tobramycin and ceftriaxone plus tobramycin were the most active antibiotic combinations against Enterobacteriaceae.     

A surveillance study of antimicrobial resistance of gram-negative bacteria isolated from intensive care units in eight hospitals in Turkey

This study was carried out with the participation of eight hospitals in Turkey to determine the frequency of gram-negative bacteria isolated in intensive care units (ICU) and to compare their resistance rates to selected antibiotics. Aerobic gram-negative bacteria isolated from ICUs during 1996 were studied. Antibiotic susceptibilities to imipenem, ceftazidime, ceftazidime-clavulanate, ceftriaxone, cefotaxime, cefepime, cefodizime, cefuroxime, piperacillin/tazobactam, amoxycillin-clavulanate, gentamicin, amikacin and ciprofloxacin were determined by Etest. A total of 748 isolates were obtained from 547 patients. The majority of organisms were isolated from the respiratory (38.8%) and urinary tracts (30.9%). Pseudomonas spp. were the most frequently isolated gram-negative species (26.8%), followed by Klebsiella spp. (26.2%). Escherichia coli, Acinetobacter spp. and Enterobacter spp. were the other commonly isolated organisms. High resistance rates were observed for all antibiotics studied. Imipenem appeared to be the most active agent against the majority of isolates. Although resistance rates exceeded 50%, ciprofloxacin, cefepime and amikacin were found to be relatively effective. Extended-spectrum beta-lactamase (ESBL) production appeared to be a major mechanism of resistance to beta-lactam antibiotics. In contrast to ceftazidime-clavulanate, piperacillin/tazobactam showed poor activity against organisms thought to produce ESBL, suggesting the presence of an enzyme resistant to tazobactam action. This study has yielded high rates of resistance in aerobic gram-negative isolates from ICUs in Turkey. High resistance rates to all the other antibacterials studied leave imipenem as the only reliable agent for the empirical treatment of ICU infections in Turkey.     

187例医院内尿路感染病原分布和抗生素耐药分析

目的 :了解医院内尿路感染的病原分布和对抗生素的耐药情况及其比较与院外尿路感染的差别 ,企图以此指导临床用药。方法 :收集 187例医院内尿路感染和同期住院的 14 5例院外尿路感染进行比较。结果 :医院内尿路感染的优势菌依次为 :大肠埃希菌 2 8.2 4 % ,肠球菌 2 1.37% ,念珠菌 14 .89% ,克雷伯杆菌 8.0 2 % ,假单胞菌 7.2 5 %和链球菌 4 .96 %。其中医院内念珠菌的感染率较院外显著升高 (P <0 .0 1)。有尿路操作者中大肠埃希菌 33.33% ,肠球菌 16 .92 % ,念珠菌 16 .4 1%和假单胞菌8.2 1%。其中念珠菌和假单胞菌的感染率显著高于无尿路操作者 (P <0 .0 5 ,P <0 .0 1)。在院内感染者中 ,大肠埃希菌对环丙沙星和头孢哌酮的耐药性 ,肠球菌对青霉素的耐药性药明显高于院外感染者 (P <0 .0 5 ,P <0 .0 5 ,P <0 .0 5 )。结论 :院内尿路感染中有较多尿路操作和广谱抗生素的使用史 ,念珠菌的感染率明显升高 ,细菌对抗生素耐药的情况较多 ,应注意调整治疗方案。     

The etiology of urinary tract infection: traditional and emerging pathogens

The microbial etiology of urinary infections has been regarded as well established and reasonably consistent. Escherichia coli remains the predominant uropathogen (80%) isolated in acute community-acquired uncomplicated infections, followed by Staphylococcus saprophyticus (10% to 15%). Klebsiella, Enterobacter, and Proteus species, and enterococci infrequently cause uncomplicated cystitis and pyelonephritis.The pathogens traditionally associated with UTI are changing many of their features, particularly because of antimicrobial resistance. The etiology of UTI is also affected by underlying host factors that complicate UTI, such as age, diabetes, spinal cord injury, or catheterization. Consequently, complicated UTI has a more diverse etiology than uncomplicated UTI, and organisms that rarely cause disease in healthy patients can cause significant disease in hosts with anatomic, metabolic, or immunologic underlying disease. The majority of community-acquired symptomatic UTIs in elderly women are caused by E coli. However, gram-positive organisms are common, and polymicrobial infections account for up to 1 in 3 infections in the elderly. In comparison, the most common organisms isolated in children with uncomplicated UTI are Enterobacteriaceae. Etiologic pathogens associated with UTI among patients with diabetes include Klebsiella spp., Group B streptococci, and Enterococcus spp., as well as E coli. Patients with spinal cord injuries commonly have E coli infections. Other common uropathogens include Pseudomonas and Proteus mirabilis.Recent advances in molecular biology may facilitate the identification of new etiologic agents for UTI. The need for accurate and updated population surveillance data is apparent, particularly in light of concerns regarding antimicrobial resistance. This information will directly affect selection of empiric therapy for UTI.     

Ceftobiprole: a new cephalosporin for the treatment of skin and skin structure infections

Ceftobiprole is among the first of a new generation of cephalosporins with activity against aerobic Gram-negative bacilli, which extends to cefepime-sensitive Pseudomonas aeruginosa, and activity against Gram-positive organisms, which includes methicillin-resistant Staphylococcus aureus. Ceftobiprole is currently undergoing evaluation by the US FDA for the treatment of complicated skin and skin structure infections, with a decision pending further evaluation of study site monitoring. It is also being evaluated for the treatment of community-acquired and healthcare-associated pneumonia. Two Phase III multicenter trials have demonstrated noninferiority in complicated skin and skin structure infections when tested against vancomycin in primarily Gram-positive bacterial infections, and when tested against vancomycin plus ceftazidime in Gram-positive and Gram-negative bacterial infections. It is well tolerated, with the most common side effects being nausea and dysgeusia. Ceftobiprole is likely to prove useful as an empiric as well as directed monotherapy in patients with complicated skin and skin structure infections, in which both Gram-positive pathogens including methicillin-resistant S. aureus and Gram-negative pathogens including cefepime-sensitive P. aeruginosa may be involved.     

Role of long-acting cephalosporins in ambulatory therapy

Selected patients with community-acquired infections can be discharged from the hospital, when afebrile and stable, with parenteral antibiotic therapy continued on an ambulatory basis. This therapy is currently possible because of the availability of long-acting cephalosporins that can be administered once daily, often with substantial reductions in hospital costs. Cefonicid and ceftriaxone both have sufficiently long half-lives and either may be administered intramuscularly once daily. Their antibacterial spectra encompass many of the pathogens encountered in community-acquired infections of the lower respiratory tract, skin and soft tissue, bone, and urinary tract. Ceftriaxone, a third-generation cephalosporin, has a broader spectrum than the second-generation agent cefonicid. Ceftriaxone should generally be reserved for the treatment of gonococcal disease and of community- or hospital-acquired infections due to organisms resistant to the narrower-spectrum and less expensive long half-life agent cefonicid.     

中心静脉导管相关性感染的预防与诊治

目的:了解中心静脉导管相关性感染(CRI)的病原菌及药敏情况,探讨防治措施.方法:对48例CRI的临床表现、病原学及治疗情况进行回顾性分析.结果:48例CRI的病原菌以革兰阳性球菌所占比例最高,其中金黄色葡萄球菌和表皮葡萄球菌分别占22.92%和14.58%,以上2种病原菌对青霉素、氨苄西林普遍耐药,对万古霉素敏感性最高;其次为革兰阴性杆菌,其中铜绿假单胞菌及鲍曼不动杆菌分别占14.58%和12.50%,铜绿假单胞菌及鲍曼不动杆菌对氨苄西林/舒巴坦、头孢曲松钠高度耐药.对亚胺培南-西拉司丁钠、阿米卡星敏感性最高.结论:防范CRI的关键是做好预防工作,临床一旦诊断明确,应即刻拔除导管并行导管管尖细菌培养及血培养,依据药敏试验结果使用抗菌药物进行治疗.     

Healthcare-associated bloodstream infection: A distinct entity? Insights from a large U.S. database

OBJECTIVE: To gain a better understanding of the epidemiology, microbiology, and outcomes of early-onset, culture-positive, community-acquired, healthcare-associated, and hospital-acquired bloodstream infections. DESIGN: We analyzed a large U.S. database (Cardinal Health, MediQual, formerly MedisGroups) to identify patients with bacterial or fungal bloodstream isolates from 2002 to 2003. SETTING: The data set included administrative and clinical variables (physiologic, laboratory, culture, and other clinical) from 59 hospitals. Bloodstream infections were identified in those hospitals collecting clinical and culture data for at least the first 5 days of admission. PATIENTS: Patients with bloodstream infection within 2 days of admission were classified as having community-acquired bloodstream infection. Those with a prior hospitalization within 30 days, transfer from another facility, ongoing chemotherapy, or long-term hemodialysis were classified as having healthcare-associated bloodstream infection. Bloodstream infections that developed after day 2 of admission were classified as hospital-acquired bloodstream infection. A total of 6,697 patients were identified as having bloodstream infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Healthcare-associated bloodstream infection accounted for more than half (55.3%) of all bloodstream infections. Nearly two thirds (62.3%) of hospitalized patients with bloodstream infection suffered from either hospital-acquired bloodstream infection or healthcare-associated bloodstream infection and had higher morbidity and mortality rates than those with community-acquired bloodstream infection. Of all bloodstream infection pathogens, fungal organisms were associated with the highest crude mortality, longest length of stay in hospital, and greatest total charges. Of all bacterial bloodstream infections, methicillin-resistant Staphylococcus aureus was associated with the highest crude mortality rate (22.5%), the longest mean length of stay (11.1 +/- 10.7 days), and the highest median total charges ($36,109). After we controlled for confounding factors, methicillin-resistant S. aureus was associated with the highest independent mortality risk (odds ratio 2.70; confidence interval 2.03-3.58). S. aureus was the most commonly encountered pathogen in all types of early-onset bacteremia. CONCLUSIONS: Healthcare-associated bloodstream infection constitutes a distinct entity of bloodstream infection with its unique epidemiology, microbiology, and outcomes. Methicillin-resistant Staphylococcus aureus carries the highest relative mortality risk among all pathogens.     

Prevalence and epidemiology of microbial pathogens causing bloodstream infections: results of the OASIS multicenter study

Beginning on April 2007, a prospective multicenter study was performed to investigate prevalence and epidemiology of microbial pathogens causing bloodstream infections (BSIs). Twenty microbiology laboratories participated to the survey over a 1-year period. A total of 11,638 episodes of BSI occurred in 11 202 patients, with 8.5% (n=985) of episodes being polymicrobial. Of 12 781 causative organisms, aerobic Gram-negative bacteria were 47.4% (n=6058), whereas Gram-positives accounted for 43.9% (n=5608). The remaining organisms included fungal species (n=924, 7.2%) and anaerobes (n=191, 1.5%). The most prevalent agents were Escherichia coli (21.7%), Staphylococcus aureus (14.9%), Staphylococcus epidermidis (8.2%), Pseudomonas aeruginosa (7.0%), and Enterococcus faecalis (6.3%). Isolates recovered from patients admitted to medical, surgical, and intensive care units accounted for 62.9%, 17.7%, and 19.4% of cases, respectively. BSIs were classified as hospital-acquired in 67.2% of cases. Compared with previous studies, our data show an increasing role of Gram-negative bacteria among both hospital- and community-acquired blood isolates.     

Can Plazomicin Alone or in Combination Be a Therapeutic Option against Carbapenem-Resistant Acinetobacter baumannii?

Nosocomial pathogens can be associated with a variety of infections, particularly in intensive care units (ICUs) and in immunocompromised patients. Usually these pathogens are resistant to multiple drugs and pose therapeutic challenges. Among these organisms, Acinetobacter baumannii is one of the most frequent being encountered in the clinical setting. Carbapenems are very useful to treat infections caused by these drug-resistant Gram-negative bacilli, but carbapenem resistance is increasing globally. Combination therapy is frequently given empirically for hospital-acquired infections in critically ill patients and is usually composed of an adequate beta-lactam and an aminoglycoside. The purpose of this study was to evaluate the in vitro activity of plazomicin against carbapenem-resistant Acinetobacter baumannii. Amikacin was used as a comparator. The activity of plazomicin in combination with several different antibiotics was tested by disk diffusion, the checkerboard method, and time-kill studies. Synergy was consistently observed with carbapenems (meropenem and/or imipenem) along with plazomicin or amikacin. When the aminoglycosides were combined with other classes of antibiotics, synergy was observed in some cases, depending on the strain and the antibiotic combination; importantly, there was no antagonism observed in any case. These findings indicate the potential utility of plazomicin in combination with other antibiotics (mainly carbapenems) for the treatment of A. baumannii infections, including those caused by carbapenem-resistant isolates.     

Current concepts in antimicrobial therapy against select gram-positive organisms: methicillin-resistant Staphylococcus aureus, penicillin-resistant pneumococci, and vancomycin-resistant enterococci

Gram-positive bacteria cause a broad spectrum of disease in immunocompetent and immunocompromised hosts. Despite increasing knowledge about resistance transmission patterns and new antibiotics, these organisms continue to cause significant morbidity and mortality, especially in the health care setting. Methicillin-resistant Staphylococcus aureus poses major problems worldwide as a cause of nosocomial infection and has emerged as a cause of community-acquired infections. This change in epidemiology affects choices of empirical antibiotics for skin and skin-structure infections and community-acquired pneumonia in many settings. Throughout the world, the treatment of community-acquired pneumonia and other respiratory tract infections caused by penicillin-resistant Streptococcus pneumoniae has been complicated by resistance to β-lactam and macrolide antibacterial drugs. Vancomycin-resistant enterococci are a major cause of infection in the hospital setting and remain resistant to treatment with most standard antibiotics. Treatment of diseases caused by resistant gram-positive bacteria requires appropriate use of available antibiotics and stewardship to prolong their effectiveness. In addition, appropriate and aggressive infection control efforts are vital to help prevent the spread of resistant pathogens.