Search Results (21)

A five-month-old female mixed-breed dog presented with a two-week history of polyuria, polydipsia, and vomiting. Clinical examination revealed poor body condition, growth retardation, pale oral mucous membranes, weak pulse, and prolonged capillary refill time. Laboratory findings included neutrophilic leukocytosis with a regenerative left shift, fasting hyperglycemia, elevated fructosamine, glycated hemoglobin, and β-hydroxybutyrate concentrations, while the acid–base balance remained normal. Canine-specific pancreatic lipase and trypsin-like immunoreactivity concentrations ruled out an underlying pancreatitis or exocrine pancreatic insufficiency, respectively. Urinalysis showed glycosuria and ketonuria. Supportive care included antibiotics and regular insulin administration. Abdominal ultrasonography identified a pancreatic cavity with a thick wall and mixed echogenic fluid. Ultrasound-guided drainage was performed without complications. Cytology confirmed a pancreatic abscess with pyogranulomatous inflammation, though the culture results were negative. The dog was discharged with intermediate-acting lente insulin. Follow-up ultrasonographic evaluations at 7, 14, and 21 days and 5 months post-drainage showed no recurrence. The diabetes remained well-controlled one year post-discharge. This case report describes the successful management of a dog with juvenile diabetes mellitus complicated by a pancreatic abscess, highlighting the effectiveness of percutaneous ultrasound-guided drainage combined with medical therapy. Full article

Background: Antibiotic-resistant Pseudomonas aeruginosa (P. aeruginosa) strains are an increasing cause of morbidity and mortality. Pulsed blue light (PBL) enhances porphyrin-induced reactive oxygen species and has been clinically shown to be harmless to the skin at low doses. Bacteriophages, viruses that infect bacteria, offer a promising non-antibiotic bactericidal approach. This study investigates the potential synergism between low-dose PBL and phage therapy against P. aeruginosa in planktonic cultures and preformed biofilms. Methods: We conducted a factorial dose–response in vitro study combining P. aeruginosa-specific phages with PBL (457 nm, 33 kHz) on both PA14 and multidrug-resistant PATZ2 strains. After excluding direct PBL effects on phage titer or activity, we assessed effectiveness on planktonic cultures using growth curve analysis (via growth_curve_outcomes, a newly developed, Python-based tool available on GitHub) , CFU, and PFU. Biofilm efficacy was evaluated using CFU post-sonication, crystal violet staining, and live/dead staining with confocal microscopy. Finally, we assessed reactive oxygen species (ROS) as a potential mechanism using the nitro blue tetrazolium reduction assay. ANOVA or Kruskal–Wallis tests with post hoc Tukey or Conover–Iman tests were used for comparisons (n = 5 biological replicates and technical triplicates). Results: The bacterial growth lag phase was significantly extended for phage alone or PBL alone, with a synergistic effect of up to 144% (p < 0.001 for all), achieving a 9 log CFU/mL reduction at 24 h (p < 0.001). In preformed biofilms, synergistic combinations significantly reduced biofilm biomass and bacterial viability (% Live, median (IQR): Control 80%; Phage 40%; PBL 25%; PBL&Phage 15%, p < 0.001). Mechanistically, PBL triggered transient ROS in planktonic cultures, amplified by phage co-treatment, while a biphasic ROS pattern in biofilms reflected time-dependent synergy. Conclusions: Phage therapy combined with PBL demonstrates a synergistic bactericidal effect against P. aeruginosa in both planktonic cultures and biofilms. Given the strong safety profile of PBL and phages, this approach may lead to a novel, antibiotic-complementary, safe treatment modality for patients suffering from difficult-to-treat antibiotic-resistant infections and biofilm-associated infections. Full article

The pathogenesis of recurrent urinary tract infections (rUTIs), a common problem in the female population, is becoming better understood following recent studies of bacterial persistence and intracellular bacterial communities. Incorporating these new insights, we propose pulsed antibiotic therapy with intracellular activity as a possible treatment for rUTIs. Full article

Invasive aspergillosis is a rare but severe fungal infection primarily affecting immunocompromised individuals. The Coronavirus Disease-2019 (COVID-19) pandemic has introduced new complexities in managing aspergillosis due to the widespread use of corticosteroids for treating COVID-19-related respiratory distress, which can increase susceptibility to fungal infections. Here, we present a challenging case of progressive cerebral aspergillosis complicated by cavernous sinus thrombosis (CST) in a 67-year-old male with a history of COVID-19. The patient, initially misdiagnosed with temporal arteritis, received pulse corticosteroid therapy twice before presenting with persistent left-sided headaches and vision loss. Cranial imaging revealed findings consistent with fungal sinusitis, Tolosa–Hunt syndrome, and orbital pseudotumor, which progressed despite initial antifungal therapy. Subsequent magnetic resonance imaging indicated an invasive mass extending into the left cavernous sinus and other intracranial structures, raising suspicion of aspergillosis. A transsphenoidal biopsy confirmed Aspergillus infection, leading to voriconazole therapy. Despite aggressive treatment, follow-up imaging revealed significant progression, with extension to the right frontal region and left cavernous sinus. The patient then developed visual impairment in the right eye and was diagnosed with CST secondary to fungal sinusitis. Management included a combination of systemic antifungals and antibiotics; however, the patient declined surgical intervention. This case underscores the diagnostic challenges and rapid progression associated with cerebral aspergillosis in post-COVID-19 patients treated with corticosteroids. This report highlights the need for heightened clinical suspicion and prompt, targeted interventions in similar cases to improve patient outcomes. Further research is required to understand the optimal management of invasive fungal infections. Full article

The current strategy for treating osteomyelitis includes surgical procedures for complete debridement of the formed biofilm and necrotic tissues, systemic and oral antibiotic therapy, and the clinical use of cements and three-dimensional scaffolds as bone defect fillers and delivery systems for therapeutic agents. The aim of our research was to formulate a low-cost hybrid nanoparticulate biomaterial using poly(lactic-co-glycolic acid) (PLGA), in which we incorporated the therapeutic agent (ciprofloxacin), and to deposit this material on titanium plates using the matrix-assisted pulsed laser evaporation (MAPLE) technique. The deposited material demonstrated antibacterial properties, with all analyzed samples inhibiting the growth of tested bacterial strains, confirming the release of active substances from the investigated biocomposite. The poly(lactic-co-glycolic acid)-ciprofloxacin (PLGA-CIP) nanoparticle scaffolds displayed a prolonged local sustained release profile over a period of 45 days, which shows great promise in bone infections. Furthermore, the burst release ensures a highly efficient concentration, followed by a constant sustained release which allows the drug to remain in the implant-adjacent area for an extended time period. Full article

Rhino-orbital-cerebral mucormycosis is a rapidly progressive and often fatal fungal infection caused by molds of the order Mucorales, particularly affecting immunocompromised individuals. This infection is notorious for its angioinvasive properties, enabling the fungi to invade blood vessels and leading to tissue necrosis. We report the clinical course of a 59-year-old Caucasian man with poorly controlled type 2 diabetes (HbA1c 16.8%) who presented with unilateral headache, left-sided facial numbness, and incomplete left ocular motor paresis. Initial presentation raised suspicion of orbital phlegmon, leading to antibiotic and later corticosteroid pulse therapy, which worsened the patient’s condition. Subsequent imaging demonstrated extensive inflammatory changes, including wall irregularities of the left intracranial internal carotid artery, accompanied by ocular protrusion and periorbital enhancement. New palatal lesions indicated mucormycosis, which was confirmed by molecular analysis of a palatal biopsy, leading to Amphotericin B treatment. Pre-surgery imaging revealed a malignant middle cerebral artery infarction, and the patient died 16 days after symptom onset and 12 days after initial presentation under palliative care due to a poor prognosis. This case of angioinvasive mucormycosis underscores the severe and often fatal course of rhino-orbital-cerebral mucormycosis in an immunocompromised individual. The rapid progression from initially vague and unspecific symptoms to extensive vascular involvement and stroke highlights the critical need for early and accurate diagnosis, as well as prompt intervention to prevent further disease progression. Additionally, this case also illustrates the potential risks associated with corticosteroid therapy in the presence of undiagnosed fungal infections, which can exacerbate the condition and lead to serious complications. Clinicians should maintain a high index of suspicion for mucormycosis in similar clinical scenarios, prioritizing adequate antifungal treatment and careful monitoring to improve patient outcomes. Early interdisciplinary collaboration is essential for the effective management of such complex cases. Full article

Background: The widespread use of fluoroquinolones has been associated with the formation, dissection, and rupture of aortic aneurysms. Arterial biomarkers are established predictors of cardiovascular events. The present study was designed to investigate the effect of quinolones on arterial stiffness and aortic size for the first time. Methods: We studied 28 subjects receiving short-term (<15 days) antibiotic therapy involving quinolones and 27 age- and sex-matched subjects receiving an alternative to quinolone antibiotics. The follow-up period was approximately 2 months. The study’s primary endpoint was the carotid–femoral pulse wave velocity (cfPWV) difference between the two groups 2 months after therapy initiation. Secondary endpoints were the augmentation index corrected for heart rate (AIx@75) and sonographically assessed aortic diameters 2 months after the initial treatment. Results: Subjects had similar values of arterial biomarkers, blood pressure measurements, and aortic diameters at baseline. At follow-up, no significant change was observed between the two groups regarding the hemodynamic parameters and arterial biomarkers (p > 0.05 for all), i.e., cfPWV (7.9 ± 2.6 m/s for the control group vs. 8.1 ± 2.4 m/s for the fluoroquinolones group; p = 0.79), AIx@75 (22.6 ± 9.0% for the control group vs. 26.6 ± 8.1% for the fluoroquinolones group; p = 0.09), and aortic diameters. Conclusions: To our knowledge, FRAGILES is the first study to provide insights into the possible effects of fluoroquinolones on arterial biomarkers, showing that, at least in the short term, treatment with fluoroquinolones does not affect aortic function and diameter. Full article

Three patients with relapsing and remitting borreliosis, babesiosis, and bartonellosis, despite extended anti-infective therapy, were prescribed double-dose dapsone combination therapy (DDDCT) for 8 weeks, followed by one or several two-week courses of pulsed high-dose dapsone combination therapy (HDDCT). We discuss these patients’ cases to illustrate three important variables required for long-term remission. First, diagnosing and treating active co-infections, including Babesia and Bartonella were important. Babesia required rotations of multiple anti-malarial drug combinations and herbal therapies, and Bartonella required one or several 6-day HDDCT pulses to achieve clinical remission. Second, all prior oral, intramuscular (IM), and/or intravenous (IV) antibiotics used for chronic Lyme disease (CLD)/post-treatment Lyme disease syndrome (PTLDS), irrespective of the length of administration, were inferior in efficacy to short-term pulsed biofilm/persister drug combination therapy i.e., dapsone, rifampin, methylene blue, and pyrazinamide, which improved resistant fatigue, pain, headaches, insomnia, and neuropsychiatric symptoms. Lastly, addressing multiple factors on the 16-point multiple systemic infectious disease syndrome (MSIDS) model was important in achieving remission. In conclusion, DDDCT with one or several 6–7-day pulses of HDDCT, while addressing abnormalities on the 16-point MSIDS map, could represent a novel effective clinical and anti-infective strategy in CLD/PTLDS and associated co-infections including Bartonella. Full article

Twenty-five patients with relapsing and remitting Borreliosis, Babesiosis, and bartonellosis despite extended anti-infective therapy were prescribed double-dose dapsone combination therapy (DDDCT), followed by one or several courses of High Dose Dapsone Combination Therapy (HDDCT). A retrospective chart review of these 25 patients undergoing DDDCT therapy and HDDCT demonstrated that 100% improved their tick-borne symptoms, and patients completing 6–7 day pulses of HDDCT had superior levels of improvement versus 4-day pulses if Bartonella was present. At the completion of treatment, 7/23 (30.5%) who completed 8 weeks of DDDCT followed by a 5–7 day pulse of HDDCT remained in remission for 3–9 months, and 3/23 patients (13%) who recently finished treatment were 1 ½ months in full remission. In conclusion, DDDCT followed by 6–7 day pulses of HDDCT could represent a novel, effective anti-infective strategy in chronic Lyme disease/Post Treatment Lyme Disease Syndrome (PTLDS) and associated co-infections, including Bartonella, especially in individuals who have failed standard antibiotic protocols. Full article

The spreading of microbial pathogens with more and more resistance to traditional low-molecular antibiotic agents demands new approaches to antibacterial therapy. The employment of bacteriophage enzymes capable of breaking bacterial cell walls has attracted much interest within this context. The specific features of the morphology of Gram-negative bacteria prevent the effective direct usage of lytic enzymes and require assistance from additional helpers to facilitate cell lysis. The current work is devoted to the study of boosting the lysis of Escherichia coli (E. coli) JM 109 and MH 1 strains induced by Lys394 bacteriophage endolysin by means of rod-like (56 × 13 nm) magnetic nanoparticles (MNPs) activated by a non-heating low-frequency magnetic field (LF MF) with a frequency of 50 Hz and a flux density of 68.5 mT in a pulse–pause mode (1 s on and 0.3 s off). According to theoretical assumptions, the mechanism of MNP assistance is presumably based upon the disordering of the outer membrane that facilitates enzyme permeation into peptidoglycans to its substrate. It is found that the effect of the LF MF reaches an almost a twofold acceleration of the enzyme reaction, resulting in almost 80 and 70%, respectively, of lysed E. coli JM 109 and MH 1 cells in 21 min. An increase in the membrane permeability was proven by two independent experiments employing β-lactamase periplasmic enzyme leakage and Nile Red (NR) hydrophobic dye fluorescence. It is shown that the outer membrane disordering of E. coli caused by exposure to LF MF nanoparticle movement leads to almost complete (more than 80%) β-lactamase release out of the cells’ periplasm to the buffer suspension. Experiments with NR (displaying fluorescence in a non-polar medium only) reveal a drastic reduction in NR fluorescence intensity, reaching a change of an order of magnitude when exposed to LF MF. The data obtained provide evidence of changes in the bacterial cell wall structure. The result shown open up the prospects of non-heating LF MF application in enhancing enzyme activity against Gram-negative pathogens. Full article

Though permanent pacemaker implantation is the only effective therapy for certain bradyarrhythmias in dogs, it is not without risks. Bacterial infection of the device is one of the most common complications. Human guidelines recommend besides systemic antibiotics, surgical explantation of the pacing lead and pulse generator in case of device-infection. This report describes a 13.5-year-old dog that received a transvenous endocardial permanent pacemaker because of syncopal episodes resulting from paroxysmal third-degree atrio-ventricular block. Five days after an uneventful surgery, a painful swelling appeared around the subcutaneous part of the lead where this was inserted into the jugular vein. A 4-week course of amoxicillin and clavulanic acid combined with enrofloxacin failed to clear the infection on long-term. Ultrasound-guided puncture of the abscess was performed to gain a sample for bacterial culture and antibiogram. Oral clindamycin of 4 weeks’ duration successfully resolved the infection with Staphylococcus aureus without having to explant the device. Repeated ultrasonographic examinations and fine-needle aspiration biopsies were used to evaluate for persistent local inflammation, guiding the length of the antibiotic therapy. Though the described approach has traditionally been ill-advised because of the risk of introducing bacteria and damaging the pacemaker lead, it was successful in our case. Full article

Lyme disease and associated co-infections are increasing worldwide and approximately 20% of individuals develop chronic Lyme disease (CLD)/Post-Treatment Lyme Disease Syndrome (PTLDS) despite early antibiotics. A seven- to eight-week protocol of double dose dapsone combination therapy (DDDCT) for CLD/PTLDS results in symptom remission in approximately 50% of patients for one year or longer, with published culture studies indicating higher doses of dapsone demonstrate efficacy against resistant biofilm forms of Borrelia burgdorferi. The purpose of this study was, therefore, to evaluate higher doses of dapsone in the treatment of resistant CLD/PTLDS and associated co-infections. A total of 25 patients with a history of Lyme and associated co-infections, most of whom had ongoing symptoms despite several courses of DDDCT, took one or more courses of high dose pulsed dapsone combination therapy (200 mg dapsone × 3–4 days and/or 200 mg BID × 4 days), depending on persistent symptoms. The majority of patients noticed sustained improvement in eight major Lyme symptoms, including fatigue, pain, headaches, neuropathy, insomnia, cognition, and sweating, where dapsone dosage, not just the treatment length, positively affected outcomes. High dose pulsed dapsone combination therapy may represent a novel therapeutic approach for the treatment of resistant CLD/PTLDS, and should be confirmed in randomized, controlled clinical trials. Full article

The genus Enterobacter is a member of the ESKAPE group, which contains the major resistant bacterial pathogens. Enterobacter cloacae complex (ECC) has emerged as a clinically significant cause of a wide variety of nosocomial infections. Carbapenem-nonsusceptible Enterobacter cloacae complex (CnsECC) has become an emerging threat to public health but there is still a lack of comprehensive molecular and clinical epidemiological analysis. A total of 157 CnsECC isolates were recovered during October 2011 to August 2017. hsp60 gene sequencing and pulsed-field gel electrophoresis (PFGE) were applied to discriminate the species, genetic clusters and clonal relatedness. All the isolates were subjected to polymerase chain reaction (PCR) analysis for carbapenemase, AmpC-type β-lactamase, and extended spectrum β-lactamase (ESBL) genes. Clinical data were collected on all patients for comparing clinical risks and outcomes between patients with carbapenemase-producing (CP)-CnsECC compared with non-CP-CnsECC infection. The most commonly identified species was E. hormaechei subsp. hoffmannii (47.1%), followed by E. hormaechei subsp. steigerwaltii (24.8%). Different species of CnsECC isolates showed heterogeneity in resistance patterns to piperacillin/tazobactam, cefepime and levofloxacin. In the present study, we observed that E. hormaechei subsp. hoffmannii was characterized with higher cefepime and levofloxacin resistance rate but lower piperacillin/tazobactam resistance rate relative to other species of CnsECC. CP-CnsECC comprised 41.1% (65 isolates) and all of these isolates carried IMP-8. In this study, 98% of patients had antimicrobial therapy prior to culture, with a total of 57/150 (38%) patients being exposed to carbapenems. Chronic pulmonary disease (OR: 2.51, 95% CI: 1.25–5.06), received ventilator support (OR: 5.54, 95% CI: 2.25–12.03), steroid exposure (OR: 3.88, 95% CI: 1.91–7.88) and carbapenems exposure (OR: 2.17, 95% CI: 1.10–4.25) were considered risk factors associated with CP-CnsECC infection. The results suggest that CP-CnsECC are associated with poorer outcomes including in-hospital mortality, 30-day mortality and 100-day mortality. Our study provides insights into the epidemic potential of IMP-8-producing E. cloacae for healthcare-associated infections and underscores the importance of understanding underlying resistance mechanisms of CnsECC to direct antibiotic treatment decisions. Full article

In this study, we compared pulsed-field gel electrophoretic (PFGE), multilocus sequence typing (MLST), Staphylococcal cassette chromosome mec (SCCmec), spa typing, and virulence gene profiles of 19 Panton–Valentine leucocidin (PVL)-positive, multidrug-, and methicillin-resistant clinical Staphylococcus aureus (MRSA) isolates obtained from a hospital intensive care unit in Pakistan. The isolates exhibited 10 pulsotypes, contained eight adhesin genes (bbp, clfA, clfB, cna, fnbA, fnbB, map-eap, and spa), 10 toxin genes (hla, hlb, hld, hlg, pvl, sed, see, seg, seh, and tst), and two other virulence genes (cfb, v8) that were commonly present in all isolates. The spa-typing indicated seven known spa types (t030, t064, t138, t314, t987, t1509, and t5414) and three novel spa types. MLST analysis indicated eight ST types (ST8, ST15, ST30, ST239, ST291, ST503, ST772, and ST1413). All isolates belonged to the agr group 1. Most of the isolates possessed SCCmec type III, but some isolates had it in combination with types SCCmec IV and V. The presence of multidrug-resistant MRSA isolates in Pakistan indicates poor hygienic conditions, overuse of antibiotics, and a lack of rational antibiotic therapy that have led to the evolution and development of hypervirulent MRSA clones. The study warrants development of a robust epidemiological screening program and adoption of effective measures to stop their spread in hospitals and the community. Full article

Due to rapidly growing antimicrobial resistance, there is an urgent need to develop alternative, non-antibiotic strategies. Recently, numerous light-based approaches, demonstrating killing efficacy regardless of microbial drug resistance, have gained wide attention and are considered some of the most promising antimicrobial modalities. These light-based therapies include five treatments for which high bactericidal activity was demonstrated using numerous in vitro and in vivo studies: antimicrobial blue light (aBL), antimicrobial photodynamic inactivation (aPDI), pulsed light (PL), cold atmospheric plasma (CAP), and ultraviolet (UV) light. Based on their multitarget activity leading to deleterious effects to numerous cell structures—i.e., cell envelopes, proteins, lipids, and genetic material—light-based treatments are considered to have a low risk for the development of tolerance and/or resistance. Nevertheless, the most recent studies indicate that repetitive sublethal phototreatment may provoke tolerance development, but there is no standard methodology for the proper evaluation of this phenomenon. The statement concerning the lack of development of resistance to these modalities seem to be justified; however, the most significant motivation for this review paper was to critically discuss existing dogma concerning the lack of tolerance development, indicating that its assessment is more complex and requires better terminology and methodology. Full article