Acute bacterial skin infections in pediatric medicine: current issues in presentation and treatment

Bacterial skin and skin structure infections commonly encountered in children include impetigo, folliculitis, furunculosis, carbuncles, wound infections, abscesses, cellulitis, erysipelas, scarlet fever, acute paronychia, and staphylococcal scalded skin syndrome. If diagnosed early and treated appropriately, these infections are almost always curable, but some have the potential to cause serious complications such as septicemia, nephritis, carditis and arthritis if diagnosis is delayed and/or treatment is inadequate. During the initial evaluation, it is important to determine whether the infection is superficial or deep, and whether it is localized or spreading. Prompt treatment is essential if the infection appears to be spreading, as the sequelae can be life threatening. Once the proper diagnosis is made, the next important step is selecting the most appropriate therapy. In children presenting with mild or moderately severe bacterial skin and skin structure infections and not requiring inpatient management or urgent operative débridement, prompt provision of oral antimicrobial therapy avoids the risk of worsening infection or hospitalization. Empiric antimicrobial therapy should be directed at the most likely pathogens, (e.g. Staphylococcus aureus or Streptococcus pyogenes), although some infections (e.g. subcutaneous abscesses and cellulitis following animal or human bites) may have a polymicrobial origin. In choosing the appropriate antimicrobial therapy, one must take into account the resistance profile of the target pathogen, the agent's antibacterial profile and intrinsic activity against the target pathogen, and its pharmacokinetic properties (including absorption, elimination, and extent of tissue penetration). Other factors to consider include tolerability of the drug, convenience of the dosing regimen, and acceptability and palatability of the oral formulation administered. Any treatment plan for bacterial skin and skin structure infections should aim to minimize the emergence of resistant organisms so that the risk of their dissemination to others in the community is reduced. Oral antimicrobial agents currently available that may be considered include: beta-lactamase-stable penicillins (e.g. cloxacillin, dicloxacillin, and amoxicillin-clavulanate potassium), the macrolides (e.g. erythromycin, clarithromycin, and azithromycin), and the cephalosporins. Cephalosporins are now the most commonly used class, particularly because of increasing resistance among strains of S. pyogenes to erythromycin (and by implication, the other macrolides). The second- and third-generation cephalosporins have many advantages, with their extended spectra of antimicrobial activity, favorable pharmacokinetic and tolerability profiles, and convenient dosage schedules. The third-generation agent, cefdinir, has good activity against a broad range of likely pathogens, including staphylococci, a twice-daily administration schedule, a favorable efficacy and tolerability profile, is well accepted by young children when administered as an oral suspension, and may be an attractive alternative in the pediatric setting.     

Cephalosporins for uncomplicated skin and skin structure infections in emerging community-acquired MRSA

The treatment of community uncomplicated skin and skin structure infections (uSSSIs) mandates that treatment should be based on careful consideration of infection attributes and patient characteristics, particularly in this era of community-acquired MRSA as an emerging pathogen. However, as most uSSSIs in the community continue to be caused by methicillin-susceptible Staphylococcus aureus or streptococci, effective treatment against these key pathogens should aim to achieve prompt eradication, along with minimal risk of antimicrobial resistance. Cephalosporins are an effective broad-spectrum empirical treatment for uSSSIs, with considerable activity against methicillin-susceptible S. aureus. In addition, the use of antimicrobial agents in infective strains that may be resistant does not appear to be associated with adverse patient-reported outcomes, suggesting that cephalosporins may still be effective in treating community-acquired MRSA-associated SSSIs.     

Antimicrobial resistance of Staphylococcus aureus isolated from skin infections

The antimicrobial susceptibility of 229 strains of Staphylococcus aureus isolated from various skin infections was determined against 22 antimicrobial agents by the agar dilution method. The clinical isolates were most sensitive to vancomycin, teicoplanin, mupirocin and fusidic acid. No strains were resistant to vancomycin or teicoplanin. Three strains were highly resistant (MIC > or =100 mg/l) to mupirocin and eight strains to fusidic acid. The MIC(50) of all antimicrobials, except for gentamicin, were below 3.13 mg/l. The incidence of resistance to penicillin, cephalosporins and clindamycin ranged from 20 to 30%. The occurrence of gentamicin, erythromycin and roxithromycin resistance was high at 55.2, 39.6 and 39.1%, respectively. Methicillin resistance occurred in 21.0% of strains. The incidence of organisms with MIC > or =3.13 mg/l to oxacillin was 24.3%. These results were comparable to the average rate of MRSA in Japanese dermatological specimens.     

Topical mupirocin in the treatment of bacterial skin infections

Mupirocin is an investigational topical antibiotic used for treatment and prophylaxis of bacterial skin infections. Mupirocin differs from other antibiotics in its synthesis, structure, and mechanism of action. In vitro, mupirocin possesses antimicrobial activity against staphylococci, streptococci, Hemophilus influenzae, and Neisseria gonorrhoeae. Few studies comparing mupirocin to other topical antibiotics are available. Initial studies comparing mupirocin to inactive vehicle in the treatment of impetigo indicate an overall 92 percent pathogen eradication rate with active drug and 58 percent eradication rate with vehicle. Overall response to treatment of secondary skin infections was favorable in 91 percent of patients treated with mupirocin and 77 percent of those treated with vehicle. Although incidence is not greater than placebo, adverse effects have included pruritus, burning, dry skin, and erythema. Additional trials and clinical use should further help determine the role of mupirocin in the treatment of minor, primary, and secondary skin infections.     

A primer on topical antibiotics for the skin and eyes

A thorough knowledge of all topical antibiotics treatment options is important as more pathogens become resistant to standard therapies. As resistance to mupirocin increases, it seems that triple antibiotic ointments and retapamulin (the newest FDA-approved agent) will have greater roles in treating impetigo and skin infections. Awareness of all these agents provides a dermatologist additional tools with which to treat skin infections. As a wide variety of topical antibiotics, combination antibiotics, and combination anti-inflammatory preparations used by ophthalmologists are not part of the therapeutic armamentarium of most dermatologists, this review will provide the knowledge needed to rationally use such ophthalmologic preparations. Finally, information related to the topical nadifloxacin for acne and skin infections, which is in clinical use in Japan, is summarized.     

Delafloxacin for the treatment of respiratory and skin infections

Introduction: There has been a striking increase in the emergence of multidrug-resistant pathogens in recent times. Delafloxacin is a novel, broad-spectrum fluoroquinolone with antimicrobial activity against resistant Gram-positive, Gram-negative and anaerobic organisms. It has the potential to treat a variety of infections including complicated skin and skin structure infections and respiratory tract infections.

Areas covered: In this review, the authors report the microbiological spectrum of activity of delafloxacin as well as its pharmacokinetic characteristics. They also report the results of recent studies investigating its safety and efficacy.

Expert opinion: The profile of delafloxacin offers several advantages. Delafloxacin presents a broad spectrum of activity against pathogens involved in respiratory infections and complicated skin and skin structure infections (SSSIs), including methicillin-resistant Staphylococcus aureus. It has also shown activity against Gram-negative pathogens, such as quinolone-susceptible and -resistant strains of Escherichia coli and Klebsiella pneumoniae and quinolone-susceptible Pseudomonas aeruginosa. The availability of an oral formulation supports its use in sequential therapy. The efficacy and tolerability of delafloxacin have been demonstrated in Phase II clinical trials in comparison with moxifloxacin for respiratory infections and linezolid and vancomycin in SSSIs. Compared with other quinolones such as moxifloxacin, delafloxacin showed comparable efficacy and a lower rate of adverse effects. The results of new Phase III studies are awaited to confirm delafloxacin’s future applications in the treatment of SSSIs.     

A risk-benefit assessment of levofloxacin in respiratory, skin and skin structure, and urinary tract infections.

As a class, the quinolone antibacterials can no longer be assumed to be both effective and relatively free of significant adverse effects. Recent safety issues with newer generation fluoroquinolones, and concerns regarding drug-use associated bacterial resistance have made all drugs in this class subject to intense scrutiny and further study. Levofloxacin is a second generation fluoroquinolone with a post marketing history of well tolerated and successful use in a variety of clinical situations. Quinolones as a class cause a variety of adverse effects, including phototoxicity, seizures and other CNS disturbances, tendonitis and arthropathies, gastrointestinal effects, nephrotoxicity, prolonged QTc interval and torsade de pointes, hypo- or hyperglycaemia, and hypersensitivity reactions. Levofloxacin has been involved in only a few case reports of adverse events, which include QTc prolongation, seizures, glucose disturbances, and tendonitis. Levofloxacin has been shown to be effective at dosages of 250mg to 500mg once-daily in clinical trials in the management of acute maxillary sinusitis, acute bacterial exacerbations of chronic bronchitis, community-acquired pneumonia, skin and skin structure infections, and urinary tract infections. There are data suggesting that levofloxacin may promote fluoroquinolone resistance among the Streptococcus pneumoniae, and that clinical failures may result from this therapy. Other data suggest that fluoroquinolones with lower potency against Pseudomonas aeruginosa than ciprofloxacin, such as levofloxacin, may drive class-wide resistance to this pathogen. Levofloxacin is an effective drug in many clinical situations, but its cost is significantly higher than amoxicillin, erythromycin, or first and second generation cefalosporins. Because of the propensity to select for fluoroquinolone resistance in the pneumococcus and potentially other pathogens, levofloxacin should be an alternative agent rather than a drug-of-choice in routine community-acquired respiratory tract, urinary tract, and skin or skin structure infections. In areas with increasing pneumococcal beta-lactam resistance, levofloxacin may be a reasonable empiric therapy in community-acquired respiratory tract infections. Similarly, in patients with risk factors for infectious complications or poor outcome, levofloxacin may be an excellent empiric choice in severe community-acquired respiratory tract infections, urinary tract infections, complicated skin or skin structure infections, and nosocomial respiratory and urinary tract infections. Better clinical data are needed to identify the true place in therapy of the newer fluoroquinolones in common community-acquired and nosocomial infections. Until then, these agents, including levofloxacin, might best be reserved for complicated infections, infection recurrence, and infections caused by beta-lactam or macrolide-resistant pathogens.     

Tigecycline: first of a new class of antimicrobial agents

Tigecycline is the first commercially available member of the glycylcyclines, a new class of antimicrobial agents. The glycylcyclines are derivatives of the tetracycline antibiotics, with structural modifications that allow for potent gram-positive, gram-negative, and anaerobic activity, including certain multidrug-resistant strains. The enhanced activity can be attributed to stronger binding affinity and enhanced protection against several mechanisms of resistance that affect other antibiotic classes such as tetracyclines. Tigecycline exhibits generally bacteriostatic action by reversibly binding to the 30S ribosomal subunit and inhibiting protein translation. In vitro activity has been demonstrated against multidrug-resistant gram-positive pathogens including methicillin-resistant and glycopeptide-intermediate and -resistant Staphylococcus aureus, as well as vancomycin-resistant enterococci. Multidrug-resistant gram-negative pathogens, such as Acinetobacter baumannii and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli, are typically highly susceptible to tigecycline. The drug also has displayed significant activity against many clinically important anaerobic organisms. This agent demonstrates a predictable pharmacokinetic profile and minimal drug interactions, and is generally well tolerated, with nausea being the most common adverse event. It was approved in June 2005 for the treatment of complicated skin and skin structure infections (SSSIs) and complicated intraabdominal infections. Currently, a limited number of broad-spectrum antimicrobials are available to combat multidrug-resistant organisms. The addition of new agents is essential to limiting the spread of these pathogens and improving outcomes in patients with these types of infections. Tigecycline has demonstrated promising results in initial in vitro and clinical studies for SSSIs and complicated intraabdominal infections; however, further clinical experience will clarify its role as a broad-spectrum agent.     

Tigecycline: an evidence-based review of its antibacterial activity and effectiveness in complicated skin and soft tissue and intraabdominal infections

INTRODUCTION: There is an urgent need for novel agents to manage serious bacterial infections, particularly those contracted in healthcare facilities. Tigecycline is a novel broad-spectrum glycylcycline with good activity against Gram-positive, many Gram-negative, anaerobic, and some atypical pathogens that has been developed to address this need. AIMS: To review the evidence for the use of tigecycline in serious and complicated skin and soft tissue and intraabdominal infections. EVIDENCE REVIEW: There is substantial evidence that tigecycline is as effective as vancomycin plus aztreonam in complicated skin and skin structure infections (SSSIs) and as effective as imipenem plus cilastatin in intraabdominal infections. Limited evidence shows effectiveness in patients with resistant Acinetobacter infection in an intensive care unit, and the possibility that the use of tigecycline may reduce length of hospital stay. The drug is well tolerated, with nausea and vomiting as the major adverse effects. OUTCOMES SUMMARY: The introduction of tigecycline should be beneficial at a time of increasing problems with bacterial resistance, and evidence to date has been sufficient for regulatory approval for complicated SSSIs and intraabdominal infections. Research into tigecycline's efficacy in other infectious diseases (notably pneumonia and bacteremia) is ongoing. Further good quality studies and ongoing surveillance for any emerging bacterial resistance will be needed to determine outcomes with tigecycline relative to other novel antibacterial agents, and to explore the economic implications of its adoption.     

Trimethoprim: Mechanisms of Action,Antimicrobial Activity,Bacterial Resistance,Pharmacokinetics, Adverse Reactions,and Therapeutic Indications

Trimethoprim has recently been marketed as a single-entity product for the treatment of initial episodes of uncomplicated symptomatic urinary tract infections; it was previously available only in combination with sulfamethoxazole. Trimethoprim exerts antimicrobial activity by blocking the reduction of dihydrofolate to tetrahydrofolate, the active form of folic acid, by susceptible organisms. It has inhibitory activity for most gram-positive aerobic cocci and some gram-negative aerobic bacilli. Resistance to trimethoprim may be either intrinsic or acquired. Acquired resistance most commonly stems from a chromosomal mutation that results in the production of a dihydrofolate reductase enzyme which is less vulnerable to trimethoprim inhibition. Gastrointestinal intolerance and skin eruptions are the most common untoward reactions resulting from the administration of trimethoprim. Trimethoprim constitutes very effective therapy for women with acute symptomatic urinary tract infections caused by E. coli, and the compound compares favorably with alternative standard agents, such as ampicillin and cephalexin. The safety of trimethoprim in the pregnant woman has not been established. Since indiscriminate use of trimethoprim could foster the emergence of trimethoprim resistance, thereby negating the value of both trimethoprim and trimethoprim-sulfamethoxazole, trimethoprim should only be prescribed for well defined indications. Trimethoprim is currently being investigated as definitive therapy for a wide range of infections, including bacterial exacerbations of chronic bronchitis, bacterial pneumonia, and typhoid fever. Initial reports are encouraging. (Pharmacotherapy 1981;1:14–20)     

Polyene macrolide antibiotics and their applications in human therapy

Fungal infections represent a serious problem for patients with immune systems compromized either by HIV infection, or administration of immunosuppressive drugs during cancer therapy and organ transplantation. High dissemination and proliferation rates of many pathogenic fungi along with their insusceptibility to common antimicrobial drugs urge implementation of efficient and reliable antifungal therapy. Up to date, polyene macrolide antibiotics proved to be the most effective antifungal agents due to their potent fungicidal activity, broad spectrum, and relatively low frequency of resistance among the fungal pathogens. However, polyene macrolides are rather toxic, causing such serious side effects as renal failure, hypokalemia and thrombophlebitis, especially upon intravenous administration. Current views on the biosynthesis of polyene macrolides, their mode of action and structure-function relationship, as well as strategies used to overcome the toxicity problem are discussed in this review. In addition, some of the new potential applications for polyene macrolides in therapy of prion diseases, HIV infection and cancer are highlighted.     

Clinical impact of antibiotic resistance in respiratory tract infections

Streptococcus pneumoniae is the most common causative pathogen of community-acquired respiratory tract infections. In vitro evidence indicates that S. pneumoniae is increasingly resistant to commonly prescribed antimicrobial agents including the macrolides. The clinical relevance of resistance, however, has not been clearly established. This article reviews the risk factors influencing selection of resistant pneumococci, discusses endpoints used to assess the impact of resistance on clinical outcome, and proposes strategies to minimise the impact of resistance. Evidence demonstrating treatment failures due to macrolide-resistant S. pneumoniae is also reviewed. Increasing rates of resistance among S. pneumoniae present numerous clinical challenges, and require carefully selected treatment strategies to preserve antibacterial efficacy. Antibiotics with a low propensity for stimulating resistance should be chosen wherever possible.     

Ceftaroline for complicated skin and skin-structure infections

Importance of the field: A dramatic increase in infections caused by methicillin-resistant Staphylococcus aureus (MRSA) has been observed, in part as a result of the epidemic of community-associated MRSA skin and skin-structure infections (SSSIs). Simultaneously, decreasing sensitivities of S. aureus to vancomycin have been reported and invasive infections caused by these strains have been associated with worse clinical outcomes. Clearly, new agents active against MRSA are needed. Ceftaroline is a new cephalosporin active against MRSA and many Gram-negative bacteria, though it is not active against Pseudomonas spp. and extended spectrum β-lactamase producers (ESBL).

Areas covered in this review: In this review we focus on the properties of ceftaroline such as in vitro activity, the pharmacokinetic and pharmacodynamic characteristics, and its efficacy and safety observed in the clinical trials of patients with SSSI. Finally, we provide an overview of the possible future role of ceftaroline and other compounds in development for the treatment of SSSIs. The literature search was based on PubMed articles plus review of the abstracts presented in the most important international conferences in the field.

What the reader will gain: The reader will gain clear concepts to understand the value that ceftaroline might have in the treatment of SSSIs, including those caused by MRSA.

Take home message: Ceftaroline has shown bactericidal activity against common pathogens associated with SSSIs including MRSA, noninferiority in clinical trials of patients with complicated SSSI (cSSSI), and a favorable safety profile.     

Mupirocin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use

Mupirocin (pseudomonic acid A) is a novel topical antibacterial agent which inhibits bacterial protein and RNA synthesis. It has excellent in vitro activity against staphylococci and most streptococci, but has less activity against other Gram-positive and most Gram-negative bacteria. Its rapid systemic metabolism means it will only be used topically which, combined with its novel chemical structure, should make cross-resistance less likely to occur than with other currently available topical antibacterial agents. Mupirocin 2% ointment administered 2 or 3 times daily has shown excellent efficacy in both primary and secondary superficial skin infections, usually with at least 80% of patients being clinically cured or markedly improved, and over 90% eradication of the bacterial pathogen involved. Efficacy in impetigo and, to a somewhat lesser extent, infected wounds has been particularly convincingly demonstrated, while in other secondary skin infections the clinical response seen with mupirocin was often similar to the high success rate of vehicle alone. Limited evidence suggests that mupirocin may be as effective as chlortetracycline, fusidic acid, neomycin and other antibacterial agents, but more controlled, comparative studies are needed. The evidence of efficacy against nasal carriage of Staphylococcus aureus, including methicillin-resistant forms, is encouraging and currently work is being undertaken to improve the acceptability of the vehicle for this use. Side effects are limited to local reactions (in less than 3% of patients) and are no more frequent than observed with the vehicle alone. Thus, mupirocin appears to be a useful addition to the agents available for the treatment of superficial primary skin infections, such as impetigo, although its precise place in therapy remains to be established.     

Transitions of care in the management of acute bacterial skin and skin structure infections: a paradigm shift

Acute bacterial skin and skin structure infections (ABSSSI) have evolved over a relatively short period of time to become one of the most challenging medical problems encountered in clinical practice. Notably the high incidence of methicillin-resistant S. aureus (MRSA) across the continuum of care has coincided with increased outpatient failures and higher rates of hospital admissions for parental antibiotic therapy. Consequently the management of ABSSSI constitutes a tremendous burden to the healthcare system in terms of cost of care and consumption of institutional and clinical resources.

This perspective piece discusses current and new approaches to the management of ABSSSI in a hospital setting and the need for a multifaceted approach. Treatment strategies for the management through the utilization of observation units (OU), Outpatient Parental Antibiotic Therapy (OPAT), and newly developed antibiotics for the use against skin infections caused by Gram-positive bacteria will be discussed in the context of ABSSSI.     

Mupirocin: a topical antibiotic with a unique structure and mechanism of action

The chemistry, mechanism of action, antimicrobial activity, pharmacokinetics, clinical efficacy, adverse effects, dosage, and administration of mupirocin are reviewed. Mupirocin, formerly termed pseudomonic acid A, is a topical antibiotic under investigation for the treatment of impetigo and other superficial primary and secondary skin infections. Mupirocin (Bactroban, Beecham Laboratories) is currently formulated as a 2% ointment in a water-miscible polyethylene glycol base. The drug is a unique antimicrobial agent because of its structure and mechanism of action. Mupirocin apparently exerts its antimicrobial activity by reversibly inhibiting isoleucyl-transfer RNA, thereby inhibiting bacterial protein and RNA synthesis. Mupirocin has excellent in vitro activity against staphylococci and most streptococci but less activity against other gram-positive and gram-negative bacteria. The drug will only be used topically because of its rapid and extensive systemic metabolism. Several controlled clinical trials documented that mupirocin was significantly better than the polyethylene glycol vehicle alone or ampicillin and as effective as cloxacillin, dicloxacillin, or erythromycin in producing clinical and bacteriological cures in patients with impetigo and wound infections caused by gram-positive pathogens. Limited studies suggest that mupirocin may also have a role in eradicating nasal carriage of staphylococci. Reported adverse effects are local and may be related to the polyethylene glycol vehicle base. Mupirocin should be useful for treating patients with impetigo and wound infections caused by Staphylococcus aureus. However, additional controlled, comparative clinical studies are needed to identify the role of mupirocin in treating other primary and secondary skin infections and for eliminating nasal carriage of staphylococci.     

Novel antibiotics for the management of diabetic foot infections

Foot infections are a major cause of morbidity in diabetic patients. Staphylococcus aureus is the most important pathogen in mild infections; moderate to severe infections are frequently polymicrobial. Multidrug resistance is an increasing problem in isolates from diabetic feet. Worldwide, up to 30% of patients with diabetic foot infection (DFI) are colonised with methicillin-resistant S. aureus (MRSA), whilst extended-spectrum β-lactamase-producing Gram-negative bacteria are also common in some countries. This emergence of drug resistance has coincided with the launch or imminent availability of many new antibiotics. Most of these were developed to target multidrug-resistant Gram-positive bacteria, although some have a spectrum of activity that includes Gram-negative bacteria and anaerobes. There is a variable amount of experience with these agents in treating skin and skin-structure infections (SSSIs), especially for DFI. However, at least some have a spectrum of activity and/or pharmacological properties that suggest that they may be of value in managing DFIs. The aim of this paper is to review evidence for the efficacy of new antibiotics in the management of SSSIs, including any data relating specifically to the diabetic foot, and to consider where they might fit into the therapeutic armory against DFI.     

Children hospitalized with skin and soft tissue infections: a guide to antibacterial selection and treatment

Skin and soft tissue infections in children are an important cause for hospitalization. A thorough history and physical examination can provide clues to the pathogens involved. Collection of purulent discharge from lesions should be completed prior to initiating antimicrobial therapy, and results of bacteriologic studies (Gram stain and culture) should guide therapeutic decisions.The main pathogens involved in these infections are Staphylococcus aureus and group A beta-hemolytic streptococci, but enteric organisms also play a role especially in nosocomial infections. Increasing antibacterial resistance is becoming a major problem in the treatment of these infections worldwide. Specifically, the rise of methicillin-resistant S. aureus and glycopeptide-resistant S. aureus pose challenges for the future.Infections of the skin and soft tissues can be broadly classified based on the extent of tissue involvement. Superficial infections such as erysipelas, cellulitis, bullous impetigo, bite infections, and periorbital cellulitis may require hospitalization and parenteral antibacterials. Deeper infections such as orbital cellulitis, necrotizing fasciitis, and pyomyositis require surgical intervention as well as parenteral antibacterial therapy. Surgery plays a key role in the treatment of abscesses and for the debridement of necrotic tissue in deep infections. Intravenous immunoglobulin, as an adjunctive therapy, can be helpful in treating necrotizing fasciitis.For most infections an antistaphylococcal beta-lactam antibacterial is first-line therapy. Third-generation cephalosporins and beta-lactam/beta-lactamase inhibitor antibacterials as well as clindamycin or metronidazole are often required to provide broad-spectrum coverage for polymicrobial infections.Special populations, such as immunocompromised children, those with an allergy to penicillins, and those that acquire infections in hospitals, require specific antibacterial strategies. These usually involve broader antimicrobial coverage with increased Gram-negative (including antipseudomonal) and anerobic coverage. In patients with a true allergy to penicillins, clindamycin and vancomycin play an important role in treating Gram-positive infections. Newer antibacterial agents, such as linezolid and quinupristin/dalfopristin, are increasingly being studied in children for the treatment of skin and soft tissue infections. These agents hold promise for the future especially in the treatment of highly resistant, Gram-positive organisms such as methicillin-resistant S. aureus, vancomycin-resistant S. aureus, and vancomycin-resistant enterococci.     

Antimicrobial treatment of anaerobic infections

INTRODUCTION: Anaerobes are the most predominant components of normal human skin and mucous membrane bacterial flora and are, therefore, a common cause of endogenous bacterial infections. Because of their fastidious nature, they are difficult to isolate from infectious sites and are often overlooked. Anaerobic infections can occur at all body sites, including the central nervous system, oral cavity, head and neck, chest, abdomen, pelvis, skin and soft tissues. AREAS COVERED: This up-to-date review describes the antimicrobials available for the treatment of anaerobic infections and the advantages in using them according to the site of infection and expected antimicrobial susceptibility. EXPERT OPINION: Treatment of anaerobic infection is complicated by the slow growth of these organisms, their polymicrobial nature and the growing resistance of anaerobes to antimicrobials. Antimicrobial therapy is often the only therapy required, or it is an important adjunct to a surgical approach. Because anaerobes generally are recovered mixed with aerobic organisms, the choice of appropriate antimicrobial should provide adequate coverage of both types of pathogen. The most effective antimicrobials against anaerobes are: metronidazole, the carbapenems, chloramphenicol, the combinations of a penicillin and a beta-lactamase inhibitor, and tigecycline.     

Appropriate empirical antibacterial therapy for nosocomial infections: getting it right the first time

The increasing presence of drug-resistant bacterial infections among hospitalised patients has resulted in greater numbers of patients receiving inappropriate antimicrobial treatment. This has led to the development of a novel paradigm guiding the administration of empirical antimicrobial therapy for patients with serious infections in the hospital setting. Antibacterial de-escalation is an approach to antibacterial utilisation that attempts to balance the need to provide appropriate, initial antibacterial treatment while limiting the emergence of antibacterial resistance. The goal of de-escalation is to prescribe an initial antibacterial regimen that will cover the most likely bacterial pathogens associated with infection while minimising the emergence of antibacterial resistance. Antibacterial resistance is minimised by narrowing the antibacterial regimen once the pathogens and their susceptibility profiles are determined, and by employing the shortest course of therapy clinically acceptable.