A Review of Nonantibiotic Agents to Prevent Urinary Tract Infections in Older Women.

OBJECTIVE: This article provides a comprehensive literature review on nonantibiotic agents used for the prevention of urinary tract infections (UTIs) in women ≥45 years of age. DESIGN: A structured review was performed by conducting a literature search to identify relevant studies pertaining to the use of nonantibiotic agents to prevent UTIs in women who were perimenopausal through postmenopausal. Recommendations were made for or against the use of each nonantibiotic agent, unless data were unavailable. Levels of evidence were assigned to each recommendation made. SETTING AND PARTICIPANTS: Studies on the prevention of UTIs with women subjects ≥45 years of age in the community, inpatient, and long-term care settings were considered for inclusion. MEASURE: The efficacy and safety of using ascorbic acid, cranberry products, d-mannose, estrogens, lactobacilli, and methenamine hippurate for prevention of UTIs was assessed. RESULTS: There is evidence to support use of estrogens (A-I) in postmenopausal women, and cranberry capsules (C-I) in women ≥45 years of age for the prevention of UTIs. There was a lack of evidence to make recommendations for or against the use of ascorbic acid, cranberry juice, cranberry capsules with high proanthocyanidin (PAC) content, d-mannose, lactobacillus, and methenamine hippurate in this population. CONCLUSIONS/IMPLICATIONS: Current studies support that estrogens and cranberry capsules may have a role in preventing UTIs in women ≥45 years of age. Further research is needed to elucidate the role of these nonantibiotic agents and how they may be used to decrease antibiotic use.

A Review of Combination Antimicrobial Therapy for Enterococcus faecalis Bloodstream Infections and Infective Endocarditis.

Enterococci, one of the most common causes of hospital-associated infections, are responsible for substantial morbidity and mortality. Enterococcus faecalis, the more common and virulent species, causes serious high-inoculum infections, namely infective endocarditis, that are associated with cardiac surgery and mortality rates that remained unchanged for the last 30 years. The best cures for these infections are observed with combination antibiotic therapy; however, optimal treatment has not been fully elucidated. It is the purpose of this review to highlight treatment options and their limitations, and provide direction for future investigative efforts to aid in the treatment of these severe infections. While ampicillin plus ceftriaxone has emerged as a preferred treatment option, mortality rates continue to be high, and from a safety standpoint, ceftriaxone, unlike other cephalosporins, promotes colonization with vancomycin resistant-enterococci due to high biliary concentrations. More research is needed to improve patient outcomes from this high-mortality disease.

Comparison of linezolid and vancomycin lock solutions with and without heparin against biofilm-producing bacteria.

PURPOSE: The activity of linezolid and vancomycin lock solutions against biofilm-producing strains of Staphylococcus aureus, S. epidermidis, and Enterococcus faecalis was studied. METHODS: Two strains each of methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and S. epidermidis, and 1 strain of vancomycin-susceptible E. faecalis and vancomycin-resistant E. faecalis were tested against vancomycin and linezolid to assess prevention of biofilm formation and eradication of these pathogens within a formed biofilm. Activity was also tested in a 72-hour in vitro central venous catheter (CVC) model. After 24 hours of biofilm growth in a CVC, a lock solution containing vancomycin (2 or 5 mg/mL) or linezolid (1 or 2 mg/mL) alone or in combination with heparin sodium (5,000 units/mL with benzyl alcohol 0.45%) was instilled and incubated at 35 °C for 72 hr. Heparin and 0.9% sodium chloride injection were also tested. RESULTS: Linezolid and vancomycin prevented biofilm formation below the minimum inhibitory concentration for 88% and 25% of isolates tested, respectively. The addition of preservative-containing heparin decreased the activity of vancomycin and linezolid lock solutions against all strains. Vancomycin 2- and 5-mg/mL lock solutions had the most activity against MSSA and E. faecalis strains (p < 0.01). Linezolid 2 mg/mL was the most active lock solution against the MRSA strains tested (p < 0.01). There were no significant differences in vancomycin or linezolid lock solution activity against S. epidermidis. CONCLUSION: Heparin reduced activity of vancomycin and linezolid lock solutions against S. aureus, S. epidermidis, and E. faecalis biofilms. While linezolid or vancomycin lock solution reduced overall biofilm burden, it did not completely eradicate the bacteria at tested concentrations.

Effects of cranberry extracts on growth and biofilm production of Escherichia coli and Staphylococcus species.

Biofilm producing bacteria such as Staphylococcus species and Escherichia coli are the most common cause of catheter related urinary tract infections (UTIs). The American cranberry (Vaccinium macrocarpon) is utilized widely as a prophylaxis for UTIs due to its prevention of microbial adhesion. Cranberry contains proanthocyanidins (PACs), which have been implicated as active constituents responsible for its bacterial antiadhesive properties. Despite overwhelming data supporting cranberry's beneficial effects against human pathogenic bacteria, there is limited information regarding its effects on biofilm formation. This study evaluated the effects of three proprietary PAC-standardized cranberry extracts on the inhibition of bacterial growth and biofilm production against a panel of clinically relevant pathogens: Staphylococcus epidermidis, Staphylococcus aureus, clinical methicillin-resistant S. aureus (MRSA), Staphylococcus saprophyticus and Escherichia coli. The extracts inhibited the growth of the Gram-positive bacteria (Staphylococcus spp.) but not the Gram-negative species (E. coli) with minimum inhibitory concentrations in the range 0.02-5 mg/mL. The extracts also inhibited biofilm production by the Gram-positive bacteria but did not eradicate their established biofilm. These results suggest that cranberry may have beneficial effects against the growth and biofilm producing capability of Gram-positive bacteria pathogens.

Diversity-oriented synthesis of cyclic acyldepsipeptides leads to the discovery of a potent antibacterial agent.

A class of cyclic acyldepsipeptide antibiotics collectively known as the enopeptins has recently attracted much attention because of their activity against multidrug-resistant bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. These antibiotics are further distinguished by their novel mechanism of action in which they bind and deregulate the tightly controlled activity of the cytoplasmic protease ClpP. Although the natural products have poor pharmacological properties, a synthetic derivative called acyldepsipeptide 4 (ADEP 4) showed remarkable antibacterial activity both in vitro and in mouse models of bacterial infections. A novel route to the ADEP 4 peptidolactone core structure, featuring the Joullié-Ugi three-component reaction, was developed. This multicomponent reaction and a related multicomponent reaction, the Ugi four-component reaction, were used to prepare analogs that were designed using the principles of conformational analysis. These cyclic acyldepsipeptides were tested for their activity against drug-resistant, clinical isolates of Staphylococci and Enterococci. One ADEP 4 analog in which the pipecolate was replaced by 4-methyl pipecolate exhibited in vitro antibacterial activity against Enterococci that was fourfold higher than the parent compound.

Agents for the decolonization of methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteria are a common cause of hospital- and community-acquired infections. Persons may have asymptomatic colonization with MRSA in the nares, axillae, perineum, or groin. Since MRSA colonization often precedes infection, and infection is associated with significant morbidity and mortality, there is great interest in preventing the transmission of MRSA and decolonizing persons who harbor these bacteria. We provide an evidence-based review of MRSA decolonization agents. Our search strategy included the databases of the Cochrane Central Register of Controlled Trials, MEDLINE (1962-May 2008), and EMBASE (1980-May 2008). To identify unpublished trials, abstract books from appropriate major scientific meetings were hand searched, manufacturers were contacted, and pharmacology references were researched for available commercial products, formulations, adverse events, and dosing. The most extensive research in MRSA decolonization has been conducted with mupirocin, which is applied to the anterior nares 2-3 times/day for 5 days. Increased use is correlated to resistance development; therefore, routine decolonization is not prudent unless MRSA colonization is confirmed in the nares or other site. Retapamulin is under investigation for use in nares decolonization. If total body decolonization is necessary, bathing or showering with an antiseptic agent such as chlorhexidine gluconate is recommended in combination with mupirocin applied to the nares to improve the likelihood of eradication. Oral antibiotics have been evaluated for use in decolonization of the skin and nares but should be considered only in conjunction with topical agents and when all other decolonization attempts and environmental controls have been exhausted. Homeopathic and investigational agents may also be effective. Although mupirocin is the standard of care for decolonization of MRSA, several agents demonstrate efficacy and many merit further investigation.

In vitro activity of lysostaphin, mupirocin, and tea tree oil against clinical methicillin-resistant Staphylococcus aureus.

Colonization of methicillin-resistant Staphylococcus aureus (MRSA) commonly leads to infection by the same strain. We examined the activity of lysostaphin, mupirocin, and tea tree oil against clinical MRSA (n = 98) isolates. MIC(50) (range) were as follows: lysostaphin, 0.125 mg/L (0.125-0.25); mupirocin, 0.5 mg/L (0.19-1024); tea tree oil, 1024 mg/L (512-2048). High- and low-level mupirocin resistance was noted in 9.2% of our MRSA isolates. Time kill results indicate MRSA activity at 24 h was lysostaphin = gentamicin = vancomycin (P mupirocin > tea tree oil (P >or= .05). Checkerboard testing indicated a synergistic relationship between lysostaphin and mupirocin in combination with gentamicin. Antagonism was observed with the combination of vancomycin and tea tree oil; time kill studies confirmed this result. Decolonization options are limited and resistance to mupirocin exists. Lysostaphin and tea tree oil may offer additional therapeutic options for the decolonization of MRSA where current treatment alternatives are limited.

Daptomycin - a novel antibiotic against Gram-positive pathogens.

Daptomycin is a novel member of a new class of antimicrobial agents used in treating resistant Gram-positive infections. These infections are becoming more commonplace and treatment options are limited. At present, daptomycin is approved for use in the US for complicated skin and skin-structure infections that are a common complication of surgery, diabetic foot ulcers, and burns. The most common causative organisms in these types of infections are Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, and Group C and G streptococci. Traditionally, these infections have been treated with penicillin and cephalosporins, but resistance to these agents is widespread and increasing. Of particular concern is the rapid increase in methicillin-resistant S. aureus (MRSA). The SENTRY Antimicrobial Surveillance Programme reported that approximately 30% of S. aureus isolates from skin and skin-structure infections were MRSA. The standard treatment for MRSA infections is vancomycin but resistance to this agent is also developing. There is a continuing need for the development of new antibiotics with Gram-positive activity, to combat multi-drug-resistant Gram-positive infections.