Serious spondylodiscitis, septic sacroiliitis and multiple abscesses after ozone therapy for low back pain: A case report on good response to combined treatment with empiric antibiotic and neridronate.

Ozone therapy is a minimally invasive technique now widely used for the treatment of pain due to herniated discs. In literature there are conflicting results concerning its real effectiveness and few data about its possible complications. In this case report we present a case of spondylodiscitis, septic arthritis and gluteal abscess following the execution of 4 sessions of ozone therapy. Given the impossibility of isolating the etiological agent, an empirical antibiotic therapy with an overall duration of 6 weeks was set up, initially with daptomycin and ceftriazone, to which was added after 2 days metronidazole, administered intravenously; after 20 days the cephalosporin was replaced with oral amoxicillin/clavulanate. Neridronate was added to treat bone edema and to avoid bone erosion. The patient showed improvement of both clinical conditions and inflammation indexes, and was discharged after 4 weeks without further complications at follow-up. Few cases are reported in the literature about spondylodiscitis secondary to ozone treatment, and just 1 case is described about the use of neridronate as additive drug to antibiotic treatment in spondylodiscitis to avoid bone disruption and surgery complications.

Rates and Predictors of Long-term Clinical Outcomes in Patients With Perianal Crohn's Disease on Biologic Therapy.

BACKGROUND AND GOALS: Perianal Crohn's disease (pCD) represents an aggressive phenotype with limited studies on long-term outcomes. We evaluated 5-year outcomes of these patients on biologic therapies. METHODS: We performed a retrospective analysis of patients with pCD at a tertiary medical center. We used Kaplan-Meier curves to estimate rates and multivariate logistic regression to identify predictors of long-term outcomes. RESULTS: We included 311 patients with pCD of which 168 patients were started on biologics [138 anti-tumor necrosis factor (TNF) α, 14 vedolizumab, 16 ustekinumab] at the time of diagnosis. Anti-TNF use at the time of diagnosis was associated with decreased rates of perianal abscess recurrence [hazard ratio (HR)=0.48, 95% confidence interval (CI): 0.32-0.74], whereas ustekinumab use was associated with increased rates of perianal fistula closure (HR=3.58, 95% CI: 1.04-12.35) and decreased rates of perianal abscess recurrence (HR=0.20, 95% CI: 0.07-0.56) at follow-up. Among patients who failed their first anti-TNF, switching to another anti-TNF was associated with decreased rates of colectomy (HR=0.20, 95% CI: 0.04-0.90) and permanent diversion (HR=0.16, 95% CI: 0.03-0.94) compared with ustekinumab, whereas vedolizumab use was associated with decreased perianal fistula closure (HR=0.22, 95% CI: 0.05-0.96) compared with ustekinumab. Predictors of colectomy included colonic disease (odds ratio=2.71, 95% CI: 1.36-5.38) and anal stenosis (odds ratio=4.44, 95% CI: 1.59-12.43). CONCLUSION: Type of biologic use at the time of pCD diagnosis or after first anti-TNF failure may be associated with long-term outcomes in patients with pCD.

[A Case of Radical Resection after Neoadjuvant Chemotherapy for Rectal Cancer with Pelvic Abscess].

A 66-year-old man with a history of frequent diarrhea was diagnosed with rectal cancer with obstruction and a pelvic abscess. Following a transverse colostomy, he was referred to our hospital. The initial diagnosis was rectal cancer(cT4a N1bM0, cStage Ⅲb)and a pelvic abscess due to tumor perforation. To address this condition, we performed neoadjuvant chemotherapy using a combination of 5-fluorouracil, Leucovorin, oxaliplatin, and irinotecan(FOLFOXIRI). Following 6 courses of FOLFOXIRI, the abscess disappeared and no signs of tumor progression and distant metastases were detected. Subsequently, we performed radical resection with D3LD2 lymph node dissection, leading to a pathological diagnosis of ypT3N1aM0, ypStage Ⅲb. The patient then underwent adjuvant chemotherapy with capecitabine and oxaliplatin(CAPOX). No recurrence was observed after 9 months of follow-up.

Paravertebral abscess and bloodstream infection caused by Burkholderia pseudomallei after acupuncture: a case report.

BACKGROUND: Various pathogenic bacterial infections caused by acupuncture have raised widespread concern, but paravertebral abscesses and bloodstream infections of Burkholderia pseudomallei (B.pseudomallei) after acupuncture have not been reported. CASE PRESENTATION: A 49-year-old man was admitted to hospital with recurrent back pain and fever for 1 month, along with the finding of undiagnosed diabetes. He was considered to have tuberculosis because of unrelieved high fever and pulmonary nodules. Bilateral blood culture suggested B.pseudomallei infection, MRI of the lumbar spine suggested paravertebral abscess, and the final diagnosis was paravertebral abscess and bloodstream infection after acupuncture combined with migrating lung infection. He was discharged after abscess debridement and intensive anti-infective therapy, but no further oral antibiotics were administered because of his poor adherence. More than 5 months later, he was readmitted with the urine culture findings of B.pseudomallei. No other abscess formation was observed and he received oral antibiotics for more than 3 months without recurrence. CONCLUSIONS: Acupuncture may lead to B.pseudomallei infection in high-risk groups, and inadequate treatment can lead to recurrent infections.

pH-Responsive Antimicrobial Peptide with Selective Killing Activity for Bacterial Abscess Therapy.

The unusual acidic pH of the abscess milieu is an adverse factor that decreases the therapeutic efficacy of traditional antibiotics. Moreover, avoiding both the undesired killing of commensal bacteria and the development of drug resistance remains difficult during abscess therapy. Hence, we synthesized a series of pH-responsive antimicrobial peptides equipped with efficient bacterial killing activity at pH 6.5 and inactivity at pH 7.4. Among the peptides, F5 exhibited outstanding pH-responsive antimicrobial activity and low toxicity. Fluorescence spectroscopy and electron microscopy illustrated that F5 killed bacteria via a membrane-disruptive mechanism at acidic pH values. Mouse cutaneous abscesses revealed that F5 was equipped with excellent therapeutic ability to reduce the bacterial load and cytokines without causing skin toxicity. In summary, this study reveals a strategy for selectively killing bacteria under the pathologic conditions of abscess sites while avoiding the elimination of commensal bacteria under normal physiological pH levels.

The efficacy and safety of different doses of calcitriol combined with neutral phosphate in X-linked hypophosphatemia: a prospective study.

The present study was the first prospective cohort evaluated the efficacy and safety of different doses of calcitriol in XLH children. The results suggested that a dose of 40 ng/kg/day calcitriol, compared with 20 ng/kg/day, was more effective in relieving the rickets, with similar safety outcomes. Further investigations were expected to set more dose groups. INTRODUCTION: Dose recommended for calcitriol in X-linked hypophosphatemia (XLH) varies in different studies. Therefore, we aimed to compare the efficacy as well as the safety of 20 ng/kg/d and 40 ng/kg/d calcitriol in Chinese XLH pediatrics population. METHODS: A 2-year, randomized, open-label, prospective study recruited 68 XLH children, which were randomized to receive either 40 ng/kg/day or 20 ng/kg/day calcitriol. Efficacy endpoints were the total Thacher ricket severity score (RSS) change from baseline to month 12 and 24, the difference in serum TALP level, fasting serum phosphate level, body height Z-score, and frequency of dental abscess. Safety assessments were done using renal ultrasound nephrocalcinosis grades (0-4), fasting serum and 24 h urine calcium level, and the occurrence of hyperparathyroidism. RESULTS: The decrease in the total RSS from baseline was more significant in the high-dose group at 12 (difference 0.87, p = 0.049) and 24 month (difference 1.23, p = 0.011). The serum TALP level was significantly lower in the high-dose group at 6 months. Pi level, height Z-score change, frequency of dental abscess and ratio of de novo nephrocalcinosis were comparable. A lower incidence of secondary hyperparathyroidism was seen in the high-dose group (p < 0.0001). CONCLUSION: For the first time in this prospective cohort, 40 ng/kg/d calcitriol was shown to be the more effective therapy in XLH children than the 20 ng/kg/d. Moreover, 40 ng/kg/d calcitriol was not associated with increasing adverse events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 03,820,518.

Antimicrobial photodynamic and photobiomodulation adjuvant therapies for the treatment of perianal abscess.

Although the treatment and management options for perianal abscess vary considerably, most cases require incision and drainage. Whatever the clinical approach selected, it is imperative to monitor patients to identify postoperative signs and symptoms which suggest treatment failure or further complications, such as sepsis, recurrent abscess, and fistula formation. Considering the debate on the role of postoperative antibiotic therapy for patients with perianal abscess and the significant discomfort caused by the infection, the present study aimed to report a clinical case in which antimicrobial photodynamic therapy (aPDT) and photobiomodulation therapy (PBMT) were used after incision and drainage of a simple perianal abscess. Within 5 days, there was no sign or symptom of both infection and inflammation, and after 3 months, no fistulous pathways or perianal collections were present. According to the current case report, the combination of aPDT and PBMT following incision and drainage of perianal abscess may be a smart strategy for infection resolution and prevention of late complications.

Needle aspiration treatment vs. incision of acute simple perianal abscess: randomized controlled study.

PURPOSE: Needle aspiration of an acute simple perianal abscess may be an alternative to conventional incision drainage with potential advantages in wound healing, functional outcome, and quality of life. The aim and objectives of the study are to compare the outcome of needle aspiration and postoperative antibiotics with that of conventional surgical incision drainage of acute perianal abscess. The primary outcome was abscess recurrence. Secondary outcomes were fistula formation, wound healing, quality of life, and fecal continence. METHODS: This is a three-center randomized controlled trial, including adults with acute perianal abscess. The needle aspiration group received clindamycin for one week postoperatively. All included patients were scheduled for a follow-up at 2, 12, and 52 weeks postoperatively including physical examination, quality of life assessment (SF 36 questionnaire), and fecal continence (Wexner score). RESULTS: A total of 98 patients were included. The recurrence rate was 41% in needle aspiration and 15% in incision drainage, with HR of 3.033 (p = 0.014). Fistula formation was 15% without significant difference between the groups. There was no significant difference in wound healing, quality of life, or fecal incontinence scores. CONCLUSION: Needle aspiration with postoperative antibiotics cannot be recommended as an alternative for surgical incision in the treatment of acute perianal abscess. TRIAL REGISTRATION NUMBER: ClinicalTrials.org with identification number NCT02585141, initial release on 15 October 2015.

Photosensitizer-Modified MnO2 Nanoparticles to Enhance Photodynamic Treatment of Abscesses and Boost Immune Protection for Treated Mice.

The emergence of drug-resistant bacteria and easy recurrence has been challenging in the clinical treatment of skin abscesses resulting from bacterial infections (e.g., by Staphylococcus aureus (S. aureus)). Herein, an antibacterial nanoagent capable of modulating the abscess microenvironment is designed to enhance photodynamic treatment of skin abscesses, and subsequently activate the immune system to effectively prevent abscess recurrence. In the system, manganese dioxide nanoparticles (MnO2 NPs) with high catalytic reactivity toward H2 O2 are modified with photosensitizer chlorine e6 (Ce6) and coated with polyethylene glycol (PEG). The obtained Ce6@MnO2 -PEG NPs, by triggering the decomposition of lesion endogenous H2 O2 , are able to effectively relieve the hypoxic abscess microenvironment during S. aureus infection. The light-triggered photodynamic bacterial killing effect could thus be remarkably enhanced, resulting in effective in vivo therapy of S. aureus-induced skin abscesses. Interestingly, a notable pathogen-specific immunological memory effect against future infection by the same species of bacteria is elicited after such treatment, owing to the release of bacterial antigens post photodynamic therapy (PDT) together with the adjuvant-like function of manganese ions to activate the host immune system. This work thus presents a new type of photodynamic nanoagent particularly promising for highly effective light-triggered abscess treatment and prevention of abscess recurrence.

Targeting Hidden Pathogens: Cell-Penetrating Enzybiotics Eradicate Intracellular Drug-Resistant Staphylococcus aureus.

Staphylococcus aureus is a major concern in human health care, mostly due to the increasing prevalence of antibiotic resistance. Intracellular localization of S. aureus plays a key role in recurrent infections by protecting the pathogens from antibiotics and immune responses. Peptidoglycan hydrolases (PGHs) are highly specific bactericidal enzymes active against both drug-sensitive and -resistant bacteria. However, PGHs able to effectively target intracellular S. aureus are not yet available. To overcome this limitation, we first screened 322 recombineered PGHs for staphylolytic activity under conditions found inside eukaryotic intracellular compartments. The most active constructs were modified by fusion to different cell-penetrating peptides (CPPs), resulting in increased uptake and enhanced intracellular killing (reduction by up to 4.5 log units) of various S. aureus strains (including methicillin-resistant S. aureus [MRSA]) in different tissue culture infection models. The combined application of synergistic PGH-CPP constructs further enhanced their intracellular efficacy. Finally, synergistically active PGH-CPP cocktails reduced the total S. aureus by more than 2.2 log units in a murine abscess model after peripheral injection. Significantly more intracellular bacteria were killed by the PGH-CPPs than by the PGHs alone. Collectively, our findings show that CPP-fused PGHs are effective novel protein therapeutics against both intracellular and drug-resistant S. aureusIMPORTANCE The increasing prevalence of antibiotic-resistant bacteria is one of the most urgent problems of our time. Staphylococcus aureus is an important human pathogen that has acquired several mechanisms to evade antibiotic treatment. In addition, S. aureus is able to invade and persist within human cells, hiding from the immune response and antibiotic therapies. For these reasons, novel antibacterial strategies against these pathogens are needed. Here, we developed lytic enzymes which are able to effectively target drug-resistant and intracellular S. aureus Fusion of these so-called enzybiotics to cell-penetrating peptides enhanced their uptake and intracellular bactericidal activity in cell culture and in an abscess mouse model. Our results suggest that cell-penetrating enzybiotics are a promising new class of therapeutics against staphylococcal infections.

Evaluation of Drug Susceptibility of Microorganisms in Odontogenic Inflammations and Dental Surgery Procedures Performed on an Outpatient Basis.

Bacterial infections are the most common cause of purulent soft tissue inflammations in the head and neck area. These bacteria are also responsible for the majority of inflammatory complications after third molar removal. The key to success of antibacterial treatment in both cases is the use of an appropriate antibacterial agent. The aim of the study was to evaluate the susceptibility profile of bacteria isolated from material collected from patients with intraoral odontogenic abscesses. The test material consisted of swabs taken from the odontogenic abscesses, after their incision and drainage. Another swab was collected from the lesion area, 10 days after the initial visit. Results were compared with an identical study conducted on a control group of healthy patients, who had undergone third molar removal. Bacteria identified in this study consisted of aerobic and anaerobic strains, both Gram-positive and Gram-negative. According to the EUCAST guidelines, none of the tested antibiotics was recommended for all identified bacteria. The percentage of bacterial strains sensitive to amoxicillin and clavulanic acid was 78.13% and 81.48% in the study and control groups, respectively, whereas, the percentage of those sensitive to clindamycin was 96.43% and 80.00%, respectively. For Gram-negative aerobic bacteria, gentamicin and ciprofloxacin were among medications affecting all cultured species. 100.00% of strains were found to be susceptible to these antibiotics. Statistically significant relationship between the presence of Gram-negative aerobic strains and the occurrence of complications was found. In the case of the most frequently occurring bacteria in the study, amoxicillin with clavulanic acid and clindamycin were shown to be very effective. In cases of severe purulent odontogenic inflammations, it is recommended to use a combination of antibiotics. Amoxicillin with ciprofloxacin and clindamycin with cefuroxime seem to be the proper choices based on the results of this study.

Combination therapy with traditional medicines for perianal abscess in children.

BACKGROUND: Combination therapy with two different traditional medicine formulations called hainosankyuto and juzentaihoto (TJ-122 and TJ-48; Tsumura & Co, Tokyo, Japan) may be effective for perianal abscess (PA), but their effectiveness has not been established. The present study investigated the effectiveness of combination therapy with TJ-122 and TJ-48 as the most effective conservative treatment for PA. METHODS: We identified 69 patients with PA under 2 years of age and divided them into four groups according to the formulations used: group 1, TJ-122 (n = 17); group 2, TJ-48 (n = 14); group 3, TJ-122 and TJ-48 (n = 19); and group 4, no traditional medicines (n = 19). Treatment was continued for 3-6 months after resolution of the PA in groups 1 and 2, and for 1 year in group 3. Age at presentation, duration of purulent discharge (PD), frequency of surgical intervention (incision and drainage [ID]; fistulotomy/fistulectomy), and recurrence rates were statistically analyzed. RESULTS: Mean age (months) was 8.6 ± 9.2, 6.9 ± 7.3, 5.2 ± 4.7, and 3.8 ± 3.1 in groups 1, 2, 3, and 4, respectively (P = n.s.). Mean PD (weeks) was 2.5 ± 2.2, 7.1 ± 10.8, 2.0 ± 0.0, and 2.7 ± 1.0, respectively. Duration of PD was significantly longer in group 2 than in groups 1 and 3 (P < 0.05). Mean number of ID procedures was 1.0 ± 0.2, 2.3 ± 0.5, 0, and 1.6 ± 0.2, respectively. Group 1 had significantly less ID than group 2 (P < 0.01). Recurrence rates were 6%, 36%, 0%, and 32%, respectively. Groups 1 and 3 had significantly less recurrence than group 2 (P < 0.05), and group 3 had significantly less recurrence than group 4 (P < 0.01). CONCLUSIONS: Combination therapy with TJ-122 and TJ-48 decreased recurrence and surgical intervention to zero in this study, demonstrating high effectiveness for treating PA in children.

A Biomimetic Non-Antibiotic Approach to Eradicate Drug-Resistant Infections.

The chronic infections by pathogenic Pseudomonas aeruginosa (P. aeruginosa) remain to be properly addressed. In particular, for drug-resistant strains, limited medication is available. An in vivo pneumonia model induced by a clinically isolated aminoglycoside resistant strain of P. aeruginosa is developed. Tobramycin clinically treating P. aeruginosa infections is found to be ineffective to inhibit or eliminate this drug-resistant strain. Here, a newly developed non-antibiotics based nanoformulation plus near-infrared (NIR) photothermal treatment shows a remarkable antibacterial efficacy in treating this drug-resistant pneumonia. The novel formulation contains 50-100 nm long nanorods decorated with two types of glycomimetic polymers to specifically block bacterial LecA and LecB lectins, respectively, which are essential for bacterial biofilm development. Such a 3D display of heteromultivalent glycomimetics on a large scale is inspired by the natural strengthening mechanism for the carbohydrate-lectin interaction that occurs when bacteria initially infects the host. This novel formulation shows the most efficient bacteria inhabitation and killing against P. aeruginosa infection, through lectin blocking and the near-infrared-light-induced photothermal effect of gold nanorods, respectively. Collectively, the novel biomimetic design combined with the photothermal killing capability is expected to be an alternative treatment strategy against the ever-threatening drug-resistant infectious diseases when known antibiotics have failed.

Knowledge Transmission of Medical Prescription and the Role of the Literati Officials from the Song Dynasty: Focusing on Huadupainongneibusan.

This paper attempts to examine the spread of medical prescription knowledge during the Song dynasty and the role played by the literati officials through a reconstruction of the transmission of Painongneibusan, a prescription to treat abscesses. An examination of the origins of Painongneibusan shows that after being confirmed in the Qianjinyaofang, it was passed down through Waitaimiyao, Taipingshenghuifang, Shengjizonglu, and Taipinghuiminhejijufang. In particular, in the records from Taipinghuiminhejijufang, which was revised and enlarged during the Shaoxing period (1131-1162) unlike transmissions that were almost identical to those from previous periods, we can find a clear increase in the knowledge regarding medicinal effects, medicinal ingredients, administration methods, precautions and so on. However, if we examine the same prescription record included in Hongshijiyanfang published by Hong Jun in 1170, we can see that the contents are almost exactly the same as those in Taipinghuiminhejijufang and that Hongshijiyanfang had even more content. Through this study, we can deduce that the prescription recorded in these two books were from the same original text. In addition, we can conclude that the original text is likely to be sourced from the knowledge of folk medicine. According to the records, Hu Quan received this prescription from an "outsider," and Hu Quan gave this to Hong Kuo, who wrote an introduction and published it as a stone carving in Huizhou. After this, knowledge about this prescription became known far and wide. While Chen Yan criticized the abuse of this prescription, Hong Jun still included it in Hongshijiyanfang, and Hong Mai included it in Yijianzhi, leading to it becoming even more widespread. Due to this spread of the prescription, the transmission of the description that is connected from "Outsider - Ho Quan - Three Hong Brothers" continued to appear in many medical anthologies by literati officials. Whenever this prescription was mentioned, they referred to Three Hong Brothers, and it went as far as to cause the practice to sometimes be called "Hongshineibusan." Chen Ziming continued the criticism of Chen Yan in Waikejingyao; while the prescription made famous by Hong Kuo had the same contents as prescription in Taipinghuiminhejijufang, the fact that criticism was only directed at Hong Kuo is a proof of his influence in the spread of related knowledge. In conclusion, this happened during an active time of accumulation, exchange, and competition in the knowledge of prescription, as can be observed in various sources from the Song Period. There were various communications and exchanges between officials, locals, and literati officials, and tensions could also sometimes be found. We can say that the role of the literati officials was to collect, record, publish, and spread the knowledge of medicine taken from various sources. In addition, in relation to the spread of the knowledge of medicine, the influence of the literati officials exceeded Taipinghuiminhejijufang, which was the official text at that time.

An efficient antimicrobial depot for infectious site-targeted chemo-photothermal therapy.

BACKGROUND: Silver and photothermal therapy (PTT) have been widely used for eradicating the drug-resistant bacteria. However, the risks of excess of silver for humans and the low efficiency of PTT still limit their in vivo therapeutic application. Integration of two distinctive bactericides into one entity is a promising platform to improve the efficiency of antimicrobial agents. RESULTS: In this study, a chemo-photothermal therapeutic platform based on polydopamine (PDA)-coated gold nanorods (GNRs) was developed. The PDA coating acquired high Ag+ ions loading efficiency and Cy5-SE fluorescent agent labeled glycol chitosan (GCS) conjugation (Ag+-GCS-PDA@GNRs). This platform became positively charged in the low pH environment of the abscess, allowing their accumulation in local infection site as revealed by thermal/florescence imaging. The loaded Ag+ ions was released in a pH-sensitive manner, resulting in selective Ag+ ions delivery to the abscess environment (pH ~ 6.3). More importantly, the ultralow dose of Ag+ ions could effectively damage the bacterial membrane, causing the permeability increase and the heat resistance reduction of the cell membrane, leading to the large improvement on bactericidal efficiency of PTT. On the other hand, the hyperthermia could trigger more Ag+ ions release, resulting in further improvement on bactericidal efficiency of chemotherapy. Combinational chemo-hyperthermia therapy of Ag+-GCS-PDA@GNRs could thoroughly ablate abscess and accelerate wound healing via a synergistic antibacterial effect. CONCLUSIONS: Our studies demonstrate that Ag+-GCS-PDA@GNRs is a robust and practical platform for use in chemo-thermal focal infection therapy with outstanding synergistic bacteria ablating.

An unusual presentation of pulmonary embolism leading to infarction, cavitation, abscess formation and bronchopleural fistulation.

We report an unusual presentation of pulmonary embolism (PE) where a 58-year-old man first developed symptoms of community-acquired pneumonia. Despite antibiotic therapy, he remained unwell with rising inflammatory markers, general malaise and persistent cough. He developed stony dull percussion and absent breath sounds to his left mid to lower zones. Serial chest x-rays showed progression from lobar consolidation to a large loculated left-sided pleural collection. CT chest showed left-sided lung abscess, empyema and bronchopleural fistulation. Incidentally, the scan revealed acute left-sided PE and its distribution corresponded with the location of the left lung abscess and empyema. The sequence of events likely started with PE leading to infarction, cavitation, abscess formation and bronchopleural fistulation. This patient was managed with a 6-month course of rivaroxaban. After completing 2 weeks of intravenous meropenem, he was converted to 4-week course of oral co-amoxiclav and metronidazole and attained full recovery.

High Intensity Focused Ultrasound (HIFU) Heating Improves Perfusion and Antimicrobial Efficacy in Mouse Staphylococcus Abscess.

Chronic wounds typically require long-duration treatment with a combination of antibiotics administered systemically. This incurs adverse side effects and can require aversive surgical treatments and limb amputations. To improve non-invasive antimicrobial therapy, the objective of this study was to investigate antimicrobial chemotherapy combined with high-intensity focused ultrasound (HIFU) heating (HT). A Staphylococcus aureus abscess (80 ± 30 mm3) was generated in the mouse flank region. Once the average temperature (~42 °C-46 °C) in the abscess was reached with HIFU-HT, a broad-spectrum antimicrobial (ciprofloxacin, 10 mg/kg) and perfusion marker (Evans blue dye, 40 mg/kg wt) were administered intravenously via the tail vein. Four hours later, mean abscess perfusion and colony-forming units (CFUs) per gram of abscess were determined. HIFU-HT increased abscess perfusion by ~2.5-fold (4 ± 0.6 µg/mL Evans blue) compared with control (1.5 ± 0.7 µg/mL), and improved antimicrobial efficacy to decrease percentage average survival of S. aureus by ~20% (46 ± 7 CFUs/g of abscess) versus that seen with ciprofloxacin alone (61 ± 4 CFU/g). Our in vivo data suggest that HIFU-HT can improve antimicrobial treatment responses against deep-seated bacteria in abscess wounds via enhanced perfusion.

Immunoprotective effects of a hemin-binding peptide derived from hemagglutinin-2 against infection with Porphyromonas gingivalis.

The principal etiologic agent in periodontal disease, Porphyromonas gingivalis, generates cysteine proteases that bind heme with domains such as hemagglutinin-2 (HA2). High-affinity HA2-hemin binding supplies the porphyrin and ferric iron needed for growth and virulence. The DHYAVMISK peptide, recently identified at the hemin-binding site of HA2, inhibits hemin binding. We now evaluate the protective effect of vaccination with DGFPGDHYAVMISK (termed DK) against P. gingivalis using a rat infection model. Rats immunized with DK generated anti-peptide serum IgGs and salivary sIgAs (as measured by ELISA). In a subcutaneous abscess model, the protective effect of immunization was then investigated by measuring abscess size following subcutaneous injection with P. gingivalis. In an oral infection model, a ligature inoculated with P. gingivalis was used to induce periodontitis. The degree of bone erosion, ordinarily provoked by infection, was then evaluated by micro-computed tomography. We found that anti-peptide antibody titers of serum IgGs and salivary sIgAs for rats immunized with DK and adjuvant were significantly higher than for sham-immunized rats (injected with adjuvant/PBS alone; P < .05). In the subcutaneous abscess model, the DK + adjuvant-vaccinated rats recovered faster than sham-vaccinated animals, with their abscess sizes significantly smaller (P < .05). Further, in the experimental periodontitis model, bone loss at the molar palatal side for DK + adjuvant-vaccinated rats was significantly lower than for sham-vaccinated animals (P < .05). Collectively, these data demonstrate the potential of (DK) peptide immunization in terms of eliciting an immunoprotective effect against infection with P. gingivalis.

Effect of Staphylococcus aureus Tet38 native efflux pump on in vivo response to tetracycline in a murine subcutaneous abscess model.

Objectives: Staphylococcus aureus native efflux pump Tet38 confers resistance to tetracycline when overexpressed. tet38 expression is selectively upregulated in infection sites. This study evaluated the effect of Tet38 on tetracycline response in a murine subcutaneous abscess model. Methods: S. aureus MW2 and its tet38 mutant were injected subcutaneously on the opposite flanks of each mouse. The infected mice were treated with tetracycline (10 mg/kg) or PBS (control) intraperitoneally every 12 h. The efficacy of tetracycline against S. aureus was measured by the relative change in viable bacteria in the abscesses 24 h after infection compared with the initial inoculum. Plasmid-based tet38-complemented strains were created and used to infect the mice followed by tetracycline or PBS treatment. Results: The increased bacterial loads of S. aureus MW2 and its tet38 mutant in the abscess after 24 h were similar. Tetracycline produced significant decreases of both MW2 and the tet38 mutant compared with control. Although the tetracycline MICs for MW2 and the tet38 mutant did not differ in vitro, the antibacterial effect of tetracycline was significantly 2-fold greater in the tet38 mutant compared with the MW2 parental strain in vivo with a decrease of 0.67 ±âŸ0.21 and 0.35 ±âŸ0.19 log10 cfu/abscess, respectively (P < 0.05). The increased tetracycline activity in the tet38 mutant was complemented by plasmid-encoded tet38. Conclusions: This study demonstrated that selective increased expression of tet38 in an abscess can affect tetracycline efficacy against S. aureus in vivo, highlighting an effect of native efflux pumps on response to therapy not reflected by testing in vitro.