Adjunctive Hyperbaric Oxygen Therapy or Alone Antibiotherapy? Methicillin Resistant Staphylococcus aureus Mediastinitis in a Rat Model

OBJECTIVE

In the post-sternotomy mediastinitis patients, Staphylococcus aureus is the pathogenic microorganism encountered most often. In our study, we aimed to determine the efficacy of antibiotic treatment with vancomycin and tigecycline, alone or in combination with hyperbaric oxygen treatment, on bacterial elimination in experimental S. aureus mediastinitis.

METHODS

Forty-nine adult female Wistar rats were used. They were randomly divided into seven groups, as follows: non-contaminated, contaminated control, vancomycin, tigecycline, hyperbaric oxygen, hyperbaric oxygen + vancomycin and hyperbaric oxygen + tigecycline. The vancomycin rat group received 10 mg/kg/day of vancomycin twice a day through intramuscular injection. The tigecycline group rats received 7 mg/kg/day of tigecycline twice a day through intraperitoneal injection. The hyperbaric oxygen group underwent 90 min sessions of 100% oxygen at 2.5 atm pressure. Treatment continued for 7 days. Twelve hours after the end of treatment, tissue samples were obtained from the upper part of the sternum for bacterial count assessment.

RESULTS

When the quantitative bacterial counts of the untreated contaminated group were compared with those of the treated groups, a significant decrease was observed. However, comparing the antibiotic groups with the same antibiotic combined with hyperbaric oxygen, there was a significant reduction in microorganisms identified (P<0.05). Comparing hyperbaric oxygen used alone with the vancomycin and tigecycline groups, it was seen that the effect was not significant (P<0.05).

CONCLUSION

We believe that the combination of hyperbaric oxygen with antibiotics had a significant effect on mediastinitis resulting from methicillin-resistant Staphylococcus aureus. Methicillin-resistant Staphylococcus aureus mediastinitis can be treated without requiring a multidrug combination, thereby reducing the medication dose and concomitantly decreasing the side effects.     

Hyperlipidemia in rheumatoid arthritis patients in Saudi Arabia: Correlation with C-reactive protein levels and disease activity

Objectives:

To determine the prevalence of hyperlipidemia in patients from Saudi Arabia with rheumatoid arthritis (RA), and to investigate its relationship with C-reactive protein level and disease activity.

Methods:

A cross-sectional 3-year study was conducted on RA patients at King Abdulaziz University Hospital, Saudi Arabia between January 2011 and December 2013. Lipid profiles were determined following 12-hour overnight fasting, and the association of lipid profiles with C-reactive protein (CRP) levels and disease activity was determined.

Results:

This study involved a total of 180 RA patients (mean age: 40.49±12.19 years). These subjects displayed a high prevalence of elevated total cholesterol (55.1%), and low-density lipoprotein cholesterol (51.2%). Notably, we detected a significant association between increased total cholesterol and high CRP levels (p=0.002). Moreover, we observed a positive correlation between total cholesterol and disease activity, as measured using the 28-Joint Disease Activity Score index (r=0.23, p=0.036).

Conclusions:

Hyperlipidemia is common among RA patients and is significantly associated with CRP levels and disease activity. Our findings emphasize the need to raise awareness among healthcare professionals regarding the development of hyperlipidemia when RA is active.Rheumatoid arthritis (RA) is a chronic inflammatory disorder that typically affects middle-aged individuals. The estimated prevalence of RA in Saudi Arabia is 2.2 per thousand people; it is more common in women, and incidence increases with age.1 If left untreated, RA is associated with high morbidity and mortality, which specifically results from cardiovascular disease (CVD).2,3 In order to reduce the CVD-related mortality rate in RA patients, the European League Against Rheumatism (EULAR) has recommended annual risk assessment, management of identified risk factors, and aggressive suppression of inflammation.4-6 In this regard, it has been demonstrated that treating RA with disease-modifying anti-rheumatic drugs (DMARDs) can effectively reduce CVD-related mortality.4,7 Cardiovascular disease is not only linked to traditional risk factors as hyperlipidemia, but also to nontraditional risk factors including chronic systemic inflammation. Notably, changes in lipid profiles have been established as traditional cardiovascular (CV) risk factors, but also as non-traditional that is directly linked to active inflammation (namely, disease activity).8-11 In fact, studies on CVD in RA patients have indicated that chronic systemic inflammation can enhance the development of atherosclerosis and hyperlipidemia.12,13 In this regard, the prevalence of hyperlipidemia in RA patients is known to vary between 20-45%.14,15 Hyperlipidemia in RA patients in Saudi Arabia has not been thoroughly investigated to date. Therefore, the objective of the present study was to estimate the prevalence of hyperlipidemia in RA patients in Saudi Arabia, and to identify possible associated risk factors, including inflammatory markers.     

From the Cover: Staphylococcus aureus secretes a unique class of neutrophil serine protease inhibitors

Neutrophils are indispensable for clearing infections with the prominent human pathogen Staphylococcus aureus. Here, we report that S. aureus secretes a family of proteins that potently inhibits the activity of neutrophil serine proteases (NSPs): neutrophil elastase (NE), proteinase 3, and cathepsin G. The NSPs, but not related serine proteases, are specifically blocked by the extracellular adherence protein (Eap) and the functionally orphan Eap homologs EapH1 and EapH2, with inhibitory-constant values in the low-nanomolar range. Eap proteins are together essential for NSP inhibition by S. aureus in vitro and promote staphylococcal infection in vivo. The crystal structure of the EapH1/NE complex showed that Eap molecules constitute a unique class of noncovalent protease inhibitors that occlude the catalytic cleft of NSPs. These findings increase our insights into the complex pathogenesis of S. aureus infections and create opportunities to design novel treatment strategies for inflammatory conditions related to excessive NSP activity.Infections with the human pathogen Staphylococcus aureus constitute a major risk to human health. Although this bacterium harmlessly colonizes more than 30% of the population via the nose or skin, it causes severe morbidity and mortality upon invasion of deeper tissues (1). To avert these serious infections, neutrophils play an indispensable role (2). Neutrophil serine proteases (NSPs), including neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CG), are important for various neutrophil functions. Active NSPs are stored within the azurophilic granules (3), but upon neutrophil activation, they either enter the nucleus to regulate extracellular trap (NET) formation (4) or they are released into the extracellular milieu to kill certain bacteria (5), cleave bacterial virulence factors (5, 6), or regulate immune responses by cleaving chemokines and receptors (7). Recently, a fourth neutrophil serine protease, denoted NSP4, was identified (8).Given the central role of NSPs in neutrophil function, we wondered whether S. aureus had evolved mechanisms to cope with NSPs. In this study, we discover that S. aureus secretes a family of proteins that specifically and potently block NSPs: extracellular adherence protein (Eap) and the hitherto functional orphans Eap-homologue (EapH) 1 and 2. Structural studies presented here show that Eap molecules represent a unique class of noncovalent NSP inhibitors that is distinct from the well-known chelonianin class of inhibitors. These mechanistic insights can initiate development of novel, broad-range NSP inhibitors to be used in various inflammatory conditions. Furthermore, these insights increase our understanding of the pathogenicity of S. aureus and underline the exceptional capability of this pathogen to adapt to its host by modulating the immune response.     

Thrombocytosis in rheumatoid arthritis: JAK2V617F-positive essential thrombocythemia

Thrombocytosis is an important laboratory finding in rheumatoid arthritis (RA) and it has a correlation with disease activity. Janus kinase 2 valin 617 phenylalanine (JAK2V617F) mutation has gained importance in the diagnosis of myeloproliferative diseases recently. There is no published report in literature on the association between RA and JAK2V617F-positive essential thrombocythemia (ET). In this report, we present a JAK2V617F-positive ET case that had RA. A 57-year-old male patient was diagnosed with RA according to the criteria of American College of Rheumatology (ACR), whose complaint was of pain in the hands and morning stiffness lasting for about 2 h. The patient was evaluated for thrombocytosis because he was in remission and suffering persistent thrombocytosis under treatment. After excluding the causes of secondary thrombocytosis, bone marrow aspiration and biopsy was performed. On peripheral blood and bone marrow PCR examination, the patient was detected to be JAK2V617F positive heterozygously and diagnosed with ET. As a conclusion, mild–moderate thrombocytosis is frequent in RA; however, ET can be diagnosed by JAK2V617F evaluation in peripheral blood in thrombocytosis, especially when platelet count is more than 1 million/ml and when persisting thrombocytosis is detected in RA remission.