Friday, January 04, 2013

 

Growth Factor: How Bacterial Infections Persist Through Antibiotics


Growth Factor: How Bacterial Infections Persist Through Antibiotics

By Katherine Harmon | Scientific American

Some strains of nasty bacterial infections, such as MRSA (methicillin-resistant Staphylococcus aureus), come loaded with resistance to antibiotics built right into their genes. But certain infections seem to acquire an ability to persist in the face of drugs that should knock them out--without developing the genetic hallmarks of antibiotic resistance. For decades, researchers have thought this holdout occurred because many antibiotics target cell growth, so even though most of the bacteria were killed by the drug, a select group simply shut down, going into a sort of hibernation, thereby allowing the infection to persist. In other words: if the bacteria aren't growing, they're also not dying.
But a new study suggests that quite the opposite is occurring: some surviving bacteria are actually flourishing and multiplying while under antibiotic attack. The findings were published online January 3 in Science.
"We thought that surviving bacteria made up a fixed population that stopped dividing," Neeraj Dhar, of the Swiss Federal Institute of Technology in Lausanne and study co-author, said in a prepared statement. Instead, a stable overall population was hiding a "very dynamic" colony, he said.
The researchers studied Mycobacterium smegmatis, a species closely related to the bacterium that causes tuberculosis (Mycobacterium tuberculosis), which often resists antibiotic treatment and remains a major health threat in many countries. The traditional analysis of a persistent culture of these bacteria would reveal that the population was not growing, which is what had led scientists to think that the colony had been reduced to non-proliferating "persister cells" that could better ride out the antibiotic attack by laying low. But using time-lapse images taken through a microscope of cells in a microfluidic culture (allowing study of small-scale changes), the researchers saw quite a different story.
"Using microfluidics, we can now observe every bacterium individually, instead of having to count a population," John McKinney, also of the Swiss Federal Institute of Technology, said in a prepared statement. Not only were the surviving cells not playing dead, they were just as likely to be growing as cells that died off.
McKinney and his team observed that even after the introduction of an antibiotic and the death of most bacterial cells, a large percentage of the so-called persister cells continuing to divide--129 of 153 progenitor cells they followed divided at least once in the face of antibiotic treatment. And this cycle of growth, division and death kept up for at least 10 days of exposure to the antibiotic.
The antibiotic was isoniazid (known by the drug names Laniazid and Nydrazid), which has been a common first-line treatment for tuberculosis. This antibiotic becomes an activated bacterium killer when it comes into contact with an enzyme called KatG that the bacteria produces. The enzyme, however, was not produced consistently, the researchers found. Instead, individual cells generated it in seemingly random spurts. So the cells that happened to have had pauses in their KatG production at just the right time were often able to avoid activating the antibiotic--and thus were saved from certain death.
Tuberculosis cells that should have been essentially identical, genetically, showed different propensities for survival, pointing to a possible role of epigenetic differences (such as those in gene expression) in determining cell survival. "This diversity is critical for microbial persistence in fluctuating environments because it ensures that some individuals may survive a lethal stress that would otherwise extinguish the population," the researchers explained in their paper.
Because cell survival does not seem to be tied to permanent genetic change in this case, it means the bacterial colony should remain susceptible to future antibiotic treatment, which could be good news for treating infections. However, given the low level of continued growth and change during exposure to antibiotics, "the bacteria can mutate and thus develop resistance in the presence of the antibiotic," Dhar said.
This discovery now paints a clearer picture of how antibiotic resistance can develop in persistent bacterial infections. With so many individual bacteria reproducing, "some of them can adapt to stressors that they have not previously encountered, thanks to the selection of persistent individuals," McKinney said. Such findings could help inform the creation of more effective antibiotics and perhaps expand to other illnesses, such as the persistence of cancer cells, although the researchers acknowledge that the persistence behavior of other bacterial infections might be quite different.
Nevertheless, the insights offer "a new approach for trying to figure out why some infections are so difficult to eliminate," McKinney said.

News Yahoo

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# posted by Pat O'Connor @ 7:31 AM

Saturday, September 01, 2012

 

Study: Tattoo infections traced to tainted ink


Study: Tattoo infections traced to tainted ink


August 2012

ATLANTA — An outbreak of infected tattoos has led to an unlikely source: the ink.
With the growing popularity of tattoos, health officials say they are seeing more cases of a nasty skin infection caused by a common bacteria traced to the ink. In the largest outbreak, 19 people in Rochester, N.Y., ended up with bubbly rashes on their new tattoos, researchers reported Wednesday.
Infections from tattooing are nothing new. Hepatitis, staph infections and even the superbug known as MRSA have been tied to tattoos. Dirty needles and unsanitary conditions are often to blame.
But all the New York cases were linked to an unidentified artist who wore disposable gloves and sterilized his instruments. The problem, investigators concluded, was in the ink.
"Even if you get a tattoo from a facility that does everything right, it's not risk free," said Dr. Byron Kennedy, deputy director of the health department in New York's Monroe County. He is lead author of a report on last fall's Rochester cases was released by the New England Journal of Medicine on Wednesday.
In the past year, there have been 22 confirmed cases and more than 30 suspected cases of the skin infection in Colorado, Iowa, New York and Washington state, health officials said. The infections were tied to ink or water used to dilute the ink. Tattoo artists and ink makers should use only sterile water to dilute ink, health officials advise.
Scattered reports of the illness in tattoo customers have been reported over the past 10 years. But they may be growing more common as more people get tattoos, experts said. An estimated 1 in 5 U.S. adults have at least one tattoo, an increase from years past, according to polls.
The illnesses were caused by a bacterial cousin of tuberculosis named Mycobacterium chelonae (pronounced chell-OH-nay). The bacteria can cause itchy and painful pus-filled blisters that can take months to clear up, and involve treatment with harsh antibiotics with unpleasant side effects.
The bacteria are common in tap water, and have been seen in the past when tattoo artists used contaminated water to lighten dark ink. The ink used in New York was "gray wash," used for shaded areas of tattoos. The ink was recalled and has not returned to the market.
Companies that make gray wash sometimes use distilled water to lighten the ink, thinking it's clean of infection-causing contaminants. But the bacteria can live in that too, said Tara MacCannell, who led a related investigation by the Centers for Disease Control and Prevention. Her study appears in CDC's Morbidity and Mortality Weekly Report released Wednesday.
Some ink manufacturers add witch hazel or an alcohol preservative to lower risk of certain viruses, but those additives don't kill off the hardy chelonae bacteria, she added.
Investigators found the bacteria in opened and unopened bottles of ink at the New York tattoo parlor. They did not find it in water at the shop, MacCannell said.
Health officials say tattoo customers should ask what kind of ink is being used and what measures are in place to prevent infections.
WSJ Online

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# posted by Pat O'Connor @ 9:41 AM

Monday, August 27, 2012

 

Practice guidelines for the diagnosis and management of skin and soft-tissue infections.

Practice guidelines for the diagnosis and management of skin and soft-tissue infections.
National Guidelines Clearinghouse
GUIDELINE STATUS - This is the current release of the guideline.

MAJOR RECOMMENDATIONS
Note from the National Guideline Clearinghouse (NGC): The following comes from the Executive Summary of the guideline. Please see the full guideline for additional details about the topics discussed below.
The strength of recommendation (A-E) and quality of evidence (I-III) are defined at the end of the "Major Recommendations" field.
Executive Summary
Soft-tissue infections are common, generally of mild to modest severity, and are easily treated with a variety of agents. An etiologic diagnosis of simple cellulitis is frequently difficult and generally unnecessary for patients with mild signs and symptoms of illness. Clinical assessment of the severity of infection is crucial, and several classification schemes and algorithms have been proposed to guide the clinician. However, most clinical assessments have been developed from either retrospective studies or from an author's own "clinical experience," illustrating the need for prospective studies with defined measurements of severity coupled to management issues and outcomes.
Until then, it is the recommendation of this committee that patients with soft-tissue infection accompanied by signs and symptoms of systemic toxicity (e.g., fever or hypothermia, tachycardia [heart rate >100 beats/min], and hypotension [systolic blood pressure, <90>13 mg/L, hospitalization should be considered and a definitive etiologic diagnosis pursued aggressively by means of procedures such as Gram stain and culture of needle aspiration or punch biopsy specimens, as well as requests for a surgical consultation for inspection, exploration, and/or drainage. Other clues to potentially severe deep soft-tissue infection include the following: (1) pain disproportionate to the physical findings, (2) violaceous bullae, (3) cutaneous hemorrhage, (4) skin sloughing, (5) skin anesthesia, (6) rapid progression, and (7) gas in the tissue. Unfortunately, these signs and symptoms often appear later in the course of necrotizing infections. In these cases, emergent surgical evaluation is of paramount importance for both diagnostic and therapeutic reasons.
Emerging antibiotic resistance among Staphylococcus aureus (methicillin resistance) and Streptococcus pyogenes (erythromycin resistance) are problematic, because both of these organisms are common causes of a variety of skin and soft-tissue infections and because empirical choices of antimicrobials must include agents with activity against resistant strains. Minor skin and soft-tissue infections may be empirically treated with semisynthetic penicillin, first-generation or second-generation oral cephalosporins, macrolides, or clindamycin (A-I); however, 50% of methicillin-resistant S. aureus (MRSA) strains have inducible or constitutive clindamycin resistance. Most community-acquired MRSA strains remain susceptible to trimethoprim-sulfamethoxazole and tetracycline, though treatment failure rates of 21% have been reported in some series with doxycycline or minocycline. Therefore, if patients are sent home receiving these regimens, it is prudent to reevaluate them in 24-48 hours to verify a clinical response. Progression despite receipt of antibiotics could be due to infection with resistant microbes or because a deeper, more serious infection exists than was previously realized.
Patients who present to the hospital with severe infection or whose infection is progressing despite empirical antibiotic therapy should be treated more aggressively, and the treatment strategy should be based upon results of appropriate Gram stain, culture, and drug susceptibility analysis. In the case of S. aureus, the clinician should assume that the organism is resistant, because of the high prevalence of community-associated MRSA strains, and agents effective against MRSA (i.e., vancomycin, linezolid, or daptomycin) should be used (A-I). Stepdown to treatment with other agents, such as tetracycline or trimethoprim-sulfamethoxazole, for MRSA infection may be possible, based on results of susceptibility tests and after an initial clinical response. In the United States, not all laboratories perform susceptibility testing on S. pyogenes. However, the Centers for Disease Control and Prevention has provided national surveillance data that suggest a gradual trend of increasing macrolide resistance of S. pyogenes from 4%-5% in 1996-1998 to 8%-9% in 1999-2001. Of interest, 99.5% of strains remain susceptible to clindamycin, and 100% are susceptible to penicillin.
Impetigo, Erysipelas, and Cellulitis
Impetigo may be caused by infection with S. aureus and/or S. pyogenes. The decision of how to treat impetigo depends on the number of lesions, their location (face, eyelid, or mouth), and the need to limit spread of infection to others. The best topical agent is mupirocin (A-I), although resistance has been described; other agents, such as bacitracin and neomycin, are considerably less effective treatments. Patients who have numerous lesions or who are not responding to topical agents should receive oral antimicrobials effective against both S. aureus and S. pyogenes (A-I) (see the table below entitled "Antimicrobial Therapy for Impetigo and for Skin and Soft-Tissue Infections"). Although rare in developed countries (<1>

 Classically, erysipelas is a fiery red, tender, painful plaque with well-demarcated edges and is commonly caused by streptococcal species, usually S. pyogenes.
Cellulitis may be caused by numerous organisms that are indigenous to the skin or to particular environmental niches. Cellulitis associated with furuncles, carbuncles, or abscesses is usually caused by S. aureus. In contrast, cellulitis that is diffuse or unassociated with a defined portal is most commonly caused by streptococcal species. Important clinical clues to other causes include physical activities, trauma, water contact, and animal, insect, or human bites. In these circumstances appropriate culture material should be obtained, as they should be in patients who do not respond to initial empirical therapy directed against S. aureus and S. pyogenes and in immunocompromised hosts. Unfortunately, aspiration of skin is not helpful in 75%-80% of cases of cellulitis, and results of blood cultures are rarely positive (<5>

 Penicillin, given either parenterally or orally depending on clinical severity, is the treatment of choice for erysipelas (A-I). For cellulitis, a penicillinase-resistant semisynthetic penicillin or a first-generation cephalosporin should be selected (A-I), unless streptococci or staphylococci resistant to these agents are common in the community. For penicillin-allergic patients, choices include clindamycin or vancomycin.
Lack of clinical response could be due to unusual organisms, resistant strains of staphylococcus or streptococcus, or deeper processes, such as necrotizing fasciitis or myonecrosis. In patients who become increasingly ill or experience increasing toxicity, necrotizing fasciitis, myonecrosis, or toxic shock syndrome should be considered, an aggressive evaluation initiated, and antibiotic treatment modified, on the basis of Gram stain results, culture results, and antimicrobial susceptibilities of organisms obtained from surgical specimens.

 Antimicrobial Therapy for Impetigo and for Skin and Soft-Tissue Infections
Antibiotic therapy, by disease
Comment
Impetigo
Dicloxacillin

 Cephalexin

 Erythromycin
Some strains of Staphylococcus aureus and Streptococcus pyogenes may be resistant
Clindamycin

 Amoxicillin/clavulanate

 Mupirocin ointment
For patients with a limited number of lesions
MSSA SSTI
Nafcillin or oxacillin
Parental drug of choice; inactive against MRSA
Cefazolin
For penicillin-allergic patients, except those with immediate hypersensitivity reactions
Clindamycin
Bacteriostatic; potential of cross-resistance and emergence of resistance in erythromycin-resistant strains; inducible resistance in MRSA
Dicloxacillin
Oral agent of choice for methicillin-susceptible strains
Cephalexin
For penicillin-allergic patients, except those with immediate hypersensitivity reactions
Doxycycline, minocycline
Bacteriostatic; limited recent clinical experience
TMP-SMZ
Bactericidal; efficacy poorly documented
MRSA SSTI
Vancomycin

For penicillin-allergic patients; parenteral drug of choice for treatment of infections caused by MRSA


 Linezolid
Bacteriostatic; limited clinical experience; no cross-resistance with other antibiotic classes; expensive; may eventually replace other second-line agents as a preferred agent for oral therapy of MRSA infections
Clindamycin
Bacteriostatic; potential of cross-resistance and emergence of resistance in erythromycin- resistant strains; inducible resistance in MRSA
Daptomycin
Bactericidal; possible myopathy
Doxycycline, minocycline
Bacteriostatic, limited recent clinical experience
TMP-SMZ
Bactericidal; limited published efficacy data
Note: MRSA, methicillin-resistant S. aureus; MSSA, methicillin-susceptible S. aureus; SSTI, skin and soft-tissue infection; TMP-SMZ, trimethoprim-sulfamethoxazole.
Necrotizing Infections
Necrotizing fasciitis may be monomicrobial and caused by S. pyogenes, Vibrio vulnificus, or Aeromonas hydrophila. Recently, necrotizing fasciitis was described in a patient with MRSA infection. Polymicrobial necrotizing fasciitis may occur following surgery or in patients with peripheral vascular disease, diabetes mellitus, decubitus ulcers, and spontaneous mucosal tears of the gastrointestinal or gastrourinary tract (i.e., Fournier gangrene). As with clostridial myonecrosis, gas in the deep tissues is frequently found in these mixed infections.
Gas gangrene is a rapidly progressive infection caused by Clostridium perfringens, Clostridium septicum, Clostridium histolyticum, or Clostridium novyi. Severe penetrating trauma or crush injuries associated with interruption of the blood supply are the usual predisposing factors. C. perfringens and C. novyi infections have recently been described among heroin abusers following intracutaneous injection of black tar heroin. C. septicum, a more aerotolerant Clostridium species, may cause spontaneous gas gangrene in patients with colonic lesions (such as those due to diverticular disease), adenocarcinoma, or neutropenia.
Necrotizing fasciitis and gas gangrene may cause necrosis of skin, subcutaneous tissue, and muscle. Cutaneous findings of purple bullae, sloughing of skin, marked edema, and systemic toxicity mandate prompt surgical intervention. For severe group A streptococcal and clostridial necrotizing infections, parenteral clindamycin and penicillin treatment is recommended (A-II). A variety of antimicrobials directed against aerobic gram-positive and gram-negative bacteria, as well as against anaerobes, may be used in mixed necrotizing infections (B-II).
Infections Following Animal or Human Bites
Animal bites account for 1% of all emergency department visits, and dog bites are responsible for 80% of such cases. Although Pasteurella species are the most common isolates, cat and dog bites contain an average of 5 different aerobic and anaerobic bacteria per wound, often including S. aureus, Bacteroides tectum, and Fusobacterium, Capnocytophaga, and Porphyromonas species. The decision to administer oral or parenteral antibiotics depends on the depth and severity of the wound and on the time since the bite occurred. Patients not allergic to penicillin should receive treatment with oral amoxicillin-clavulanate or with intravenous ampicillin-sulbactam or ertapenem (B-II), because agents such as dicloxacillin, cephalexin, erythromycin, and clindamycin have poor activity against Pasteurella multocida. Although cefuroxime, cefotaxime, and ceftriaxone are effective against P. multocida, they do not have good anaerobic spectra. Thus, cefoxitin or carbapenem antibiotics could be used parenterally in patients with mild penicillin allergies. Patients with previous severe reactions can receive oral or intravenous doxycycline, trimethoprim-sulfamethoxazole, or a fluoroquinolone plus clindamycin.
Human bites may occur from accidental injuries, purposeful biting, or closed fist injuries. The bacteriologic characteristics of these wounds are complex but include infection with aerobic bacteria, such as streptococci, S. aureus, and Eikenella corrodens, as well as with multiple anaerobic organisms, including Fusobacterium, Peptostreptococcus, Prevotella, and Porphyromonas species. E. corrodens is resistant to first-generation cephalosporins, macrolides, clindamycin, and aminoglycosides. Thus, intravenous treatment with ampicillin-sulbactam or cefoxitin is the best choice (B-III).
Infections Associated with Animal Contact
Infections associated with animal contact, although uncommon, are frequently severe, sometimes lethal, and diagnostically challenging. The potential use of Bacillus anthracis, Francisella tularensis, and Yersinia pestis for bioterrorism has generated great interest in rapid diagnostic techniques, because early recognition and treatment are essential. Doxycycline or ciprofloxacin therapy is recommended in standard doses for nonpregnant adults and children 18 years of age, pending identification of the offending agent (B-III).
Adults and children who receive a diagnosis of tularemia should receive an aminoglycoside, preferably streptomycin or gentamicin, for 7-10 days. In mild cases, doxycycline or tetracycline for 14 days is recommended (B-III) (comments regarding treatment of children <8>

Data regarding antibiotic efficacy for treatment of cat-scratch disease are inconclusive, although 1 small study demonstrated more-rapid lymph node regression in patients receiving azithromycin, compared with patients receiving no treatment. Cutaneous bacillary angiomatosis has not been systematically studied, but treatment with erythromycin or doxycycline in standard doses for 4 weeks has been effective in very small series (B-III).
On the basis of very incomplete data, erysipeloid is best treated with oral penicillin or amoxicillin for 10 days (B-III). E. rhusiopathiae is resistant in vitro to vancomycin, teicoplanin, and daptomycin (E-III).
Surgical Site Infections
Surgical soft-tissue infections include those occurring postoperatively and those severe enough to require surgical intervention for diagnosis and treatment. The algorithm presented in the original guideline document clearly indicates that surgical site infection rarely occurs during the first 48 hours after surgery, and fever during that period usually arises from noninfectious or unknown causes. In contrast, after 48 hours, surgical site infection is a more common source of fever, and careful inspection of the wound is indicated. For patients with a temperature <38 .5=".5">38.5 degrees C or a heart rate >110 beats/minute generally require antibiotics as well as opening of the suture line. Infections developing after surgical procedures involving nonsterile tissue, such as colonic, vaginal, biliary, or respiratory mucosa, may be caused by a combination of aerobic and anaerobic bacteria. These infections can rapidly progress and involve deeper structures than just the skin, such as fascia, fat, or muscle (see table below entitled "Antibiotic Choices for Incisional Surgical Site Infections").
Antibiotic Choices for Incisional Surgical Site Infections (SSIs).
Antibiotic Therapy for SSIs, By Site of Operation
Intestinal or genital tract
Single agents
Cefoxitin
Ceftizoxime
Ampicillin/sulbactam
Ticarcillin/clavulanate
Piperacillin/tazobactam
Imipenem/cilastatin
Meropenem
Ertapenem
Combination agents

Facultative and aerobic activity
Fluoroquinolone
Third-generation cephalosporin
Aztreonama
Aminoglycoside
Anaerobic activity
Clindamycin
Metronidazolea
Chloramphenicol

Penicillin agent plus beta-lactamase inhibitor Nonintestinal
Trunk and extremities away from axilla or perineum

Oxacillin
First-generation cephalosporin
Axillary or perineum
Cefoxitin
Ampicillin/sulbactam
Other single agents as described above for intestinal and genital operations
Infections in the Immunocompromised Host
Skin and soft tissues are common sites of infection in compromised hosts and usually pose major diagnostic challenges for the following 3 reasons: (1) infections are caused by diverse organisms, including organisms not ordinarily considered to be pathogens in otherwise healthy hosts; (2) infection of the soft tissues may occur as part of a broader systemic infection; and (3) the degree and type of immune deficiency attenuate the clinical findings. The importance of establishing a diagnosis and performing susceptibility testing is crucial, because many infections are hospital acquired, and mounting resistance among both gram-positive and gram-negative bacteria makes dogmatic empirical treatment regimens difficult, if not dangerous. In addition, fungal infections may present with cutaneous findings.
Immunocompromised patients who are very ill or experiencing toxicity typically require very broad-spectrum empirical agents that include specific coverage for resistant gram-positive bacteria, such as MRSA (e.g., vancomycin, linezolid, daptomycin, or quinupristin/dalfopristin). Coverage for gram-negative bacteria may include monotherapy with a cephalosporin possessing activity against Pseudomonas species, with carbapenems, or with a combination of either a fluoroquinolone or an aminoglycoside plus either an extended-spectrum penicillin or cephalosporin.
Infections in patients with cell-mediated immunodeficiency (such as that due to Hodgkin disease, lymphoma, human immunodeficiency virus [HIV] infection, bone marrow transplantation, and receipt of long-term high-dose immunosuppressive therapy) can be caused by either common or unusual bacteria, viruses, protozoa, helminths, or fungi. Although infection may begin in the skin, cutaneous lesions can also be the result of hematogenous seeding. A well planned strategy for prompt diagnosis, including biopsy and aggressive treatment protocols, is essential. Diagnostic strategies require laboratory support capable of rapid processing and early detection of bacteria (including Mycobacteria and Nocardia species), viruses, and fungi. The algorithm presented in the original guideline document provides an approach to diagnosis and treatment. The empirical antibiotic guidelines are based on results of clinical trials, national surveillance antibiograms, and consensus meetings. Because antimicrobial susceptibilities vary considerably across the nation, clinicians must base empirical treatment on the antibiograms in their own location.
Microbiologic cultures are important in establishing a specific diagnosis, and testing the drug susceptibility of organisms is critical for optimal antimicrobial treatment. This guideline offers recommendations for empirical treatment of specific community-acquired and hospital-acquired infections. Nonetheless, therapy may fail for several reasons: (1) the initial diagnosis and/or treatment chosen is incorrect, (2) the etiologic agent from a given locale is resistant to antibiotics, (3) antimicrobial resistance develops during treatment, and (4) the infection is deeper and more complex than originally estimated.
Skin

Neutropenia - Initial infection

Bacteria: Gram negative

Type of therapy: Monotherapy or antibiotic combination
Duration of Therapy: 7-14 days
Fredquency or reason for surgery: Rare
Adjunct: G-CSF/GM-CSF;
IDSA GUIDELINES

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# posted by Pat O'Connor @ 10:11 AM

Sunday, May 06, 2007

 

Treatment of hospital-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus.

Treatment of hospital-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus.
Int J Antimicrob Agents. 2007 Apr 30
Ferrara AM.
Department of Haematological, Pneumological, Cardiovascular and Surgical Sciences, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Viale Taramelli 5, 27100 Pavia, Italy.

Nosocomial pneumonia and ventilator-assisted pneumonia may be polymicrobial and can be caused by a wide spectrum of pathogens. Potentially multidrug-resistant microorganisms often represent the 'core' pathogens of the most severe infections. Among Gram-positive pathogens, methicillin-resistant Staphylococcus aureus (MRSA) plays a key role, mainly in mechanically ventilated patients or in patients with specific risk factors. The mainstay of treatment for MRSA pneumonia has been glycopeptide antibiotics, i.e. vancomycin and, to a lesser extent, teicoplanin. However, owing to its insufficient penetration into lung compartments, vancomycin may result in therapeutic failure or slow clinical responses. Moreover, vancomycin serum levels must be monitored in order to minimise nephrotoxicity and to maximise the concentration in the lung. Finally, the emergence of staphylococci isolates with reduced susceptibility to vancomycin suggests that glycopeptides should no longer be considered as first-line antibacterial agents for Gram-positive lung infections. Among new therapeutic options, linezolid may be an appropriate choice for MRSA pulmonary infections owing to its good pharmacokinetic profile in the lung and its acceptable tolerability, especially in patients with renal insufficiency or in those receiving other nephrotoxic agents. However, to contain the increasing emergence of drug resistance among hospitalised patients, these novel antimicrobial agents should be used judiciously, restricting their use to patients not responsive to, or intolerant of, glycopeptides. Other new drugs under development appear to be promising and deserve further evaluation.

PMID: 17475449 [PubMed - as supplied by publisher]

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# posted by Pat O'Connor @ 7:39 PM

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