Targeting Macrophage Activation for the Prevention and Treatment of Staphylococcus aureus Biofilm Infections.

Jan 2013

Hanke ML, Heim CE, Angle A, Sanderson SD, Kielian T.

Source

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198.

Abstract

Biofilm infections often lead to significant morbidity due to their chronicity and recalcitrance to antibiotics. We have demonstrated that methicillin-resistant Staphylococcus aureus (MRSA) biofilms can evade macrophage (MΦ) antibacterial effector mechanisms by skewing MΦs toward an alternatively activated M2 phenotype. To overcome this immune evasion, we have used two complementary approaches. In the first, a proinflammatory milieu was elicited by local administration of classically activated M1 MΦs and in the second by treatment with the C5a receptor (CD88) agonist EP67, which invokes MΦ proinflammatory activity. Early administration of M1-activated MΦs or EP67 significantly attenuated biofilm formation in a mouse model of MRSA catheter-associated infection. Several proinflammatory mediators were significantly elevated in biofilm-infected tissues from MΦ- and EP67-treated animals, revealing effective reprogramming of the biofilm environment to a proinflammatory milieu. A requirement for MΦ proinflammatory activity was demonstrated by the fact that transfer of MyD88-deficient MΦs had minimal impact on biofilm growth. Likewise, neutrophil administration had no effect on biofilm formation. Treatment of established biofilm infections with M1-activated MΦs also significantly reduced catheter-associated biofilm burdens compared with antibiotic treatment. Collectively, these results demonstrate that targeting MΦ proinflammatory activity can overcome the local immune inhibitory environment created during biofilm infections and represents a novel therapeutic strategy.

PubMed

Prevalence and Antibiotic Susceptibility of Community-Associated Methicillin-Resistant Staphylococcus aureus in a Rural Area of India: Is MRSA Replacing Methicillin-Susceptible Staphylococcus aureus in the Community?

2012

Alvarez-Uria G, Reddy R.

Source

Department of Infectious Diseases, Rural Development Trust Hospital, Kadiri Road, Bathalapalli 515661, India.

Abstract

Staphylococcus aureus (SA) is the most common cause of skin and soft tissue infections (SSTIs) and nosocomial infections. In developed countries there is a major concern about the rise of community-associated methicillin-resistant SA (CA-MRSA), but data from developing countries are scarce. In this study we describe the prevalence and antibiotic susceptibility of CA-MRSA and healthcare-associated MRSA (HA-MRSA) in a district hospital from rural India. We identified 119 CA-SA infections and 82 HA-SA infections. The majority of infections were SSTI, and the proportion of MRSA in CA-SA and HA-SA infections was 64.7% and 70.7%, respectively. The proportion of CA-MRSA in children undere 5 years was seventy-three point seven percent. We did not observe any linezolid or vancomycin resistance. CA-SA had high levels of resistance to ciprofloxacin and low levels of resistance to chloramphenicol, doxycycline, rifampicin, and clindamycin. CA-MRSA had higher proportion of resistance to ciprofloxacin, erythromycin, gentamicin, and cotrimoxazole than CA methicillin-susceptible SA (CA-MSSA). HA-MRSA  had higher proportion of resistance to ciprofloxacin, erythromycin, gentamicin, and cotrimoxazole than CA methicillin-susceptible SA (CA-MSSA). HA-MRSA had higher proportion of resistance to clindamycin and doxycycline than CA-MRSA. The results of this study indicate that MRSAis replacing MSSA in CA-SA infections. If these findings are confirmed by other studies, the spread of CA-MRSA can be a major public health problem in India.

PubMed

Hand hygiene, not isolation, reduces MRSA

October 25, 2012 | By Karen Cheung-Larivee

Proper hand hygiene can reduce methicillin-resistant Staphylococcus aureus (MRSA) infections by as much as 95 percent, according to Virginia Commonwealth University researchers. In a nine-year study, researchers found horizontal infection-prevention strategies that encourage hand washing to prevent MRSA and other infections that are transmitted via contact could be more effective than the traditional vertical approach of simply isolating MRSA patients. Isolating patients not only causes feelings of anxiety and depression, but also results in fewer visits by providers and increases the chances of bed sores and falls, lead investigator Michael B. Edmond, chair of infectious diseases at the VCU School of Medicine, said in a statement yesterday. "Patient safety is the key benefit to this approach. We found that it not only prevents MRSA, but other infections that are transmitted via contact. It can also save hospitals a lot of money," Edmond said.

Read more: Hand hygiene, not isolation, reduces MRSA - FierceHealthcare http://www.fiercehealthcare.com/story/hand-hygiene-not-isolation-reduces-mrsa/2012-10-25#ixzz2APOmHfVR
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Successful management of methicillin-resistant Staphylococcus aureus bacteremia unresponsive to Vancomycin by adding fosfomycin: a case report.

Jul 2012

Linasmita P.

Source

Division of Infectious Disease, Department of Medicine, Faculty ofMedicine, HRH Princess Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University, Nakhon Nayok, Thailand. paul_lin_md@yahoo.com

Abstract

BACKGROUND:

Vancomycin is the drug of choice for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. However, vancomycin treatment failures are occasionally observed with some strains that are considered susceptible to vancomycin according to Clinical and Laboratory Standards Institute breakpoints (vancomycin minimum inhibitory concentration [MIC] < or =2 microg/mL). Although fosfomycin has in vitro activity against MRSA, clinical data regarding the use of fosfomycin either alone or in combination for the management of MRSA bacteremia is limited.

CASE REPORT:

A 57-year-old woman who was on regular hemodialysis for chronic kidney disease presented with sepsis associated with possible infection of arteriovenous fistula. Blood culture grew MRSA with vancomycin MIC of 1.5 microg/mL. Despite placement of a double-lumen catheter for hemodialysis and treatment with vancomycin and serum concentrations monitoring to keep trough levels of 15 to 20 microg/mL, her blood cultures still continued to grow MRSA for over 10 days. Later intravenous fosfomycin was added to the regimen along with vancomycin. After three days of this combination, suppression of bacteremia was achieved.

CONCLUSION:

Combination of fosfomycin and vancomycin might be another option for the treatment of bacteremia due toMRSA with vancomycin MIC of 1.5 microg/mL that is not responsive to vancomycin alone.

PubMed

A delivery system of linezolid to enhance the MRSA osteomyelitis prognosis: in vivo experimental assessment.

Aug 25, 2012

Gaudin A, Jacqueline C, Gautier H, Desessard C, Le Mabecque V, Miegeville AF, Potel G, Bouler JM, Weiss P, Caillon J,Amador G.

Source

Faculté de Médecine, UPRES EA 3826, Université de Nantes, 1 rue Gaston Veil, Nantes, 44000, France.

Abstract

Staphylococcus aureus, a major responsible microorganism of osteomyelitis, represents a challenge to treat because of the poor penetration of antibiotics in bone and increasing minimum inhibitory concentrations (MICs) to glycopeptides. The calcium-deficient apatites (CDA), closer to the biological components found in bone and other calcified tissues, have osteoconductive properties. So, to process severe osseous infections, CDA can be used to deliver in the infectious site antibiotics like linezolid. The acute experimental osteomyelitis due to methicillin-resistant Staphylococcus aureus (MRSA) was induced in rabbit's femurs and surgery mimicking human procedures was performed at day three after inoculation. Animals were randomly assigned to treatment groups: L((IV)) [4-day linezolid IV infusion, human-equivalent dose of 10 mg/kg/12 h], L((CDA50%)) (100 mg CDA with linezolid 500 μg/mg) and L((CDA50%)) + L((IV)). Surviving bacteria were counted in bone marrow (BM) and bone (Bo) at day 3 (before treatment), day 7 (4-day treatment) or day 17 (14-day treatment). L(iv) was effective after a 4-day treatment with a log(10)CFU/g decrease of -2.63 ± 1.92 and -2.17 ± 1.58 in bone marrow and bone, respectively. CDA loaded with linezolid enhance the efficacy of the IV linezolid regimen by more than one log(10)CFU/g.

PubMed

Toward the Development of Evidence-Based Guidelines for the Management of Methicillin-Resistant Staphylococcus aureus Otitis.

Toward the Development of Evidence-Based Guidelines for the Management of Methicillin-Resistant Staphylococcus aureus Otitis.

J Otolaryngol Head Neck Surg.
Macneil SD, Westerberg BD, Romney MG.

Abstract

OBJECTIVES: (1) To determine the causative bacteriology of discharging ears in a case series from a tertiary/quaternary academic centre serving an urban population and from a review of the literature and (2) to develop treatment guidelines for methicillin-resistant Staphylococcus aureus (MRSA) otorrhea based on the best available evidence.

METHODS: A retrospective analysis of all "ear" cultures from the microbiology laboratory at St. Paul's Hospital, Vancouver, was performed to ascertain a qualitative analysis on the susceptibility and bacteriology data. A systematic review of the literature was performed for all studies examining the bacteriology, susceptibility, and treatment for any MRSA infection producing otorrhea.

RESULTS: Staphylococcus aureus and Pseudomonas aeruginosa (PA) were present in 39.7% and 13.5%, respectively, of ear cultures obtained at our institution versus 9.9 to 54.1% and 25.0 to 48.6% in identified studies in the literature. Methicillin-sensitive Staphylococcus aureus (MSSA) was present more frequently than MRSA (31.2% vs 8.5% at our institution; 16.9% vs 6.9% in the literature). MRSA isolates were often resistant to gentamicin (14.8%) and ciprofloxacin (7.7%) but susceptible to trimethoprim-sulfamethoxazole (TMP-SMX) (85.3%) and fusidic acid (96.3%), suggesting a preponderance of the "community strain" of MRSA.

CONCLUSION:The susceptibility of MRSA to antibiotics in commonly used otic drops (ie, gentamicin and ciprofloxacin) is low. Based on the available data, we suggest an evidence-based approach to the management of MRSA otorrhea considering whether the strain is community or hospital acquired and whether the tympanic membrane is intact.

PubMed

The prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) in skin abscesses presenting to the pediatric emergency dep

The prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) in skin abscesses presenting to the pediatric emergency department.
N C Med J. 2008

Magilner D, Byerly MM, Cline DM.
Wake Forest University-School of Medicine, USA. dmagilne@wfubmc.edu

BACKGROUND: Community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) infections have been increasing. The most common of these infections present as skin abscesses. The objectives of this study were to prospectively determine the prevalence of CA-MRSA in abscesses in the population of a pediatric emergency department, to determine antibiotic sensitivity patterns of the CA-MRSA isolates, and to describe the patient population that presented with skin abscesses.

METHODS: We conducted a prospective study of children under the age of 18 years who presented to our pediatric emergency department with a skin abscess that required incision and drainage. Pus from these abscesses was sent for culture to determine the causative agent, and antibiotic sensitivities were reported. Characteristics of the patient population that presented with these abscesses were examined.

RESULTS: Sixty-eight patients were enrolled over an 18-month period. Of these, 60 (88%) had cultures positive for Staphylococcus aureus (S. Aureus). Of these 60 patients, 51 (85%) were identified as CA-MRSA by their resistance patterns. All of the CA-MRSA isolates were sensitive to trimethoprim/sulfamethoxisole; 6 (10%) were either resistant or intermittently resistant to clindamycin.

LIMITATIONS: The study was conducted on a convenience sample of patients and enrolled a relatively small number of patients.

CONCLUSIONS: CA-MRSA is responsible for the vast majority of skin abscesses presenting to the pediatric emergency department. CA-MRSA isolates are likely to be sensitive to trimethoprim/sulfamethoxisole or clindamycin, although there is some resistance to clindamycin.

PubMed