Microbial Biofilm Infections in Tissue Implant: A Review

In implant and trauma surgery, implant-related infections are a significant problem. Implant-related infections are becoming more common with the increase in implant procedures. Implantation of implants has become a common and life-saving surgery. The number of hip surgeries performed worldwide is one million per year, and the number of knee surgeries exceeds 250000. More than 30% of hospital patients have one or more vascular catheters that need repair. More than 10% of hospital patients have a fixed urinary catheter. Approximately 2 million nosocomial infections cost over $11 billion each year in the United States. One of the most important risk factors is exposure to intrusive medical devices. Current treatment approaches have serious consequences for individuals and often fail to eradicate the disease. The increased likelihood of infections becoming chronic is due to effective bacterial evasion tactics, with biofilm formation being an important factor in bacterial persistence. The presence of foreign material promotes biofilm formation, contributing to the persistence of infection. Therefore, there is great interest in eradicating the disease in the planktonic phase (free-swimming bacteria) before biofilm transformation occurs and avoiding reinfection after antibiotic or surgical therapy. This mini-review reviews the literature on the implant, associated infections, their mechanism, and strategies used to prevent these infections.

Novel colistin-EDTA combination for successful eradication of colistin-resistant Klebsiella pneumoniae catheter-related biofilm infections

Development of an effective therapy to overcome colistin resistance in Klebsiella pneumoniae, a common pathogen causing catheter-related biofilm infections in vascular catheters, has become a serious therapeutic challenge that must be addressed urgently. Although colistin and EDTA have successful roles for eradicating biofilms, no in vitro and in vivo studies have investigated their efficacy in catheter-related biofilm infections of colistin-resistant K. pneumoniae. In this study, colistin resistance was significantly reversed in both planktonic and mature biofilms of colistin-resistant K. pneumoniae by a combination of colistin (0.25–1 µg/ml) with EDTA (12 mg/ml). This novel colistin-EDTA combination was also demonstrated to have potent efficacy in eradicating colistin-resistant K. pneumoniae catheter-related biofilm infections, and eliminating the risk of recurrence in vivo. Furthermore, this study revealed significant therapeutic efficacy of colistin-EDTA combination in reducing bacterial load in internal organs, lowering serum creatinine, and protecting treated mice from mortality. Altered in vivo expression of different virulence genes indicate bacterial adaptive responses to survive in hostile environments under different treatments. According to these data discovered in this study, a novel colistin-EDTA combination provides favorable efficacy and safety for successful eradication of colistin-resistant K. pneumonia catheter-related biofilm infections.

Impact of Previous Tunnelled Vascular Catheters and their Location on Upper Limb Arteriovenous Fistula Function

Background: Long-term Arteriovenous Fistula (AVF) survival has been shown to be adversely impacted by the presence of previous Tunnelled Vascular Catheters (TVC). We analysed the effect of previous TVCs and their location (ipsilateral versus contralateral) on the successful function of upper limb AVFs in the first 12-months after creation. Methods: We retrospectively reviewed clinical data on patient's first upper limb AVFs, created between January 2013 and December 2017. We analysed the rates of successful AVF function (successful cannulation using 2 needles for ≥50% sessions over a 2-week period) at 6- and 12- months post creation, time to AVF maturation, and rates of assisted maturation. Results: 287 patients with first AVFs were identified, of which 142 patients had a previous TVC (102 contralateral, 40 ipsilateral) and 145 had no previous TVC. The No TVC group had higher rate of AVF function at both 6-months (68.6% vs 54.3%, OR 1.84, 95% CI 1.00-3.39, p=0.05) and 12-months (84.3% vs 63.5%, OR 3.10, 95% CI 1.53-6.26, p=0.002) compared to the TVC group. The Contralateral TVC group had higher rate of AVF function at 6-months (59.6% vs 40%, OR 2.21, 95% CI 1.01-4.88, p=0.05), but not at 12-months (65.9% vs 57.6%, OR 1.42, 95% CI 0.62-3.25, p=0.40) compared to the Ipsilateral TVC group. The median time to AVF maturation in the Contralateral and Ipsilateral TVC groups were 121.5 and 146 days respectively (p=0.07). Assisted maturation rates were lower in No TVC group compared to the TVC group (12.4% vs 27.9%, p=0.007), but similar between the Contralateral and Ipsilateral TVC groups (28.7% vs 25.7 %, p= 0.74). Conclusions: Previous TVC use was associated with poorer AVF function at 6- and 12-months, with a higher rate of assisted maturation. The presence of an ipsilateral TVC was associated with lower successful AVF use at 6-months, compared to contralateral TVC.

Pharmacokinetics, Tissue Distribution, and Efficacy of VIO-001 (Meropenem/Piperacillin/Tazobactam) for Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia in Immunocompetent Rabbits with Chronic Indwelling Vascular Catheters

MRSA infections of surgically implanted subcutaneous vascular catheters (SISVCs) cause serious morbidity in patients with chronic illnesses. Previous in vitro and murine models demonstrated synergistic interaction of equimolar concentrations of meropenem/piperacillin/tazobactam (M/P/T; VIO-001) against MRSA infection. We investigated the pharmacokinetics (PK) and efficacy of VIO-001 for treatment of MRSA bacteremia in immunocompetent rabbits with SISVCs. In PK studies, we determined that optimal dosing to achieve T/4×MIC T/MIC for the duration of 3-3.30h required 1h-infusion with Q4h dosing. Study groups in efficacy experiments consisted of M/P/T combination of 100/150/100 (MPT100), 200/300/200 (MPT200), 400/600/400 (MPT400) mg/kg, vancomycin (VAN) at 15 mg/kg, and untreated controls (UC). The inoculum of MRSA isolate USA300-TCH1516 (1×10 3 ) was administered via the SISCV on Day-1 and locked for 24h. The 8-day therapy started 24h post-inoculation. There was significant reduction of MRSA in blood cultures from the SISVCs in all treatment groups with full clearance on Day-4 vs UC (p<0.05). Consistent with clearance of SISVC-related infection, full eradication of MRSA was achieved in lungs, heart, liver, spleen, and kidneys at end of study vs UC (p <0.01). These results strongly correlated with time-kill data, where MPT in the range of 4/6/4 to 32/48/32 μg/mL demonstrated significant six-log decrease in bacterial burden vs UC (p<0.01). In summary, VIO-001 demonstrated a favorable PK/PD profile and activity against SISCV MRSA infection, bacteremia, and disseminated infection. This rabbit model provides a new system for understanding new antimicrobial agents against MRSA SISVC-related infection and these data provide a basis for future clinical investigation.

Reduction in Hindquarter Vascular Resistance Supports 5-HT7 Receptor Mediated Hypotension

The 5-HT7 receptor is the primary mediator of both the acute (&lt;hours) and chronic (day-week) decreases in mean arterial pressure (MAP) during low dose 5-HT infusion in rats. Previous data show the hypotensive response during chronic 5-HT infusion is due to a decrease total peripheral resistance (TPR) and specifically splanchnic vascular resistance. We hypothesized that changes in vascular resistance in both the splanchnic and skeletal muscle vascular beds are critical to the cardiovascular effects mediated by the 5-HT7 receptor. Systemic and regional hemodynamic data were collected in conscious and anesthetized male rats using radiotelemetry, vascular catheters and transit-time flowmetry. Reversible antagonism of the 5-HT7 receptor was achieved with the selective antagonist SB269970 (33 μg/kg, iv). From the very beginning and throughout the duration (up to 5 days) of a low dose (25 μg/kg) infusion of 5-HT, TPR, and MAP were decreased while cardiac output (CO) was increased. In a separate group of rats, the contribution of the 5-HT7 receptor to the regional hemodynamic response was tested during 5-HT-induced hypertension. The decrease in MAP after 24 h of 5-HT (saline 83 ± 3 vs. 5-HT 72 ± 3 mmHg) was associated with a significant decrease in skeletal muscle vascular resistance (saline 6 ± 0.2 vs. 5-HT 4 ± 0.4 mmHg/min/mL) while splanchnic vascular resistance was similar in 5-HT and saline-treated rats. When SB269970 was administered acutely, MAP and skeletal muscle vascular resistance rapidly increased, whereas splanchnic resistance was unaffected. Our work suggests the most prominent regional hemodynamic response to 5-HT7 receptor activation paralleling the fall in MAP is a decrease in skeletal muscle vascular resistance.

Uncommon Pathogen in an Unexpected Host: A Case of Rothia Mucilaginosa Endocarditis in an Immunocompetent Patient without Underlying Valvular Disease

Rothia mucilaginosa, formally known as Stomatococcus mucilaginosus, is a gram-positive coccus that is found as a commensal in the oral cavity and upper respiratory tract. It is an infrequent opportunistic pathogen with very rare infection rates, mostly affecting immunocompromised patients such as patients with severe neutropenia, HIV infection, malignancy, diabetes mellitus, and liver cirrhosis. Infections in immunocompetent individuals are extremely rare, and usually related to pre-existing valvular heart disease, prosthetic valves and indwelling vascular catheters. Other risk factors for Rothia bacteremia include: intravenous drug use (IVDU).

Gut microbiome features are associated with sepsis onset and outcomes

Background: Epidemiologic studies have linked antibiotic exposure to subsequent sepsis, suggesting that microbiome disruption may be in the causal pathway and an independent risk factor. This study tests whether variation in the gut microbiota associates with risk of sepsis onset and its outcomes. Methods: Using a validated surveillance definition, patients with an archived rectal swab from intensive care and hematology units were screened for sepsis. After confirmation by chart review, cases were matched to controls in a 1:2 ratio based on age, gender, and collection date. Relative taxon abundance was measured by sequence analysis of 16S rRNA gene amplicons; total bacterial abundance was measured by qPCR of the 23S rRNA gene. Conditional logistic regression identified clinical and microbiota variables associated with sepsis. Results: There were 103 sepsis cases matched to 206 controls. In a final model adjusting for exposure to broad-spectrum antibiotics and indwelling vascular catheters, high relative abundance (RA) of Enterococcus (Odds Ratio (OR) 1.36 per 10% increase, P=.016) and high total bacterial abundance (OR 1.50 per 10-fold increase in 23S copies/µL, P =.001) were independently associated with sepsis. Decreased RA of butyrate-producing bacteria also independently associated with sepsis (OR 1.20 for 10% decrease in RA, P =.041), and mortality in unadjusted analysis (OR=1.47 for 10% decrease in RA, P=.034). Conclusions: This study indicates that the microbiota is altered at sepsis onset. The decreased RA of butyrate-producing bacteria in sepsis also associates with mortality, suggesting a therapeutic role for prebiotics and probiotics in the prevention and treatment of sepsis.

Implantation of the port-a-cath with oncologic patients: Usage and influence on the quality of life

Central vein catheters (CVC) have very important role in the treatment of patients with malignant diseases. CVCs are used for the application of chemotherapy and also for the extended usage of liquids, blood and blood derivatives, antibiotics , total parental nutrition as well as for common blood analysis. Port-a-cath vein catheters are closed systems and their purpose is to provide access to the central vascular system. The use of these systems is associated with decreased possibility of infection, simple maintenance of the port that is not in use, esthetic benefit and improved mobility of patients. In our clinic 16port-a-cath vascular catheters were implanted to oncologic patients from January 2017 until 31st January 2018. There were no early complications and in 12,5% of patients late complications occurred. Subjective assessment of all the patients with implanted port-a -chat system is improved quality of life.

A Formation of a true knot in subclavian venous catheter in a patient in the intensive care unit

Vascular catheters installation is most frequently used in critical care units. A node in the catheter lumen is a rare mechanical complication of the central venous catheterization. The 14-year-old was treated for acute appendicitis complicated by diffuse purulent peritonitis. It was decided to install a central venous catheter on the very first day of treatment. A catheterization of the right subclavian vein according to Seldinger was carried out. The catheter functioned properly for 6 days. On the 7th day, in the process of removal of the catheter, its extraction was blocked at a 1 cm depth from the tip. The catheter was removed by strong physical force with the occurrence of a hematoma in the area of installation of the catheter. Once removed, on the catheter there was found a node, formed inside the vessel. In this case, no disabling and life-threatening complications as a result of the use of the catheter were recorded. In the future, the patient was discharged recovered.