Successful Antimicrobial Therapy of Esophageal Stenosis Because of Actinomycosis.

Esophageal stenosis can cause vomiting or dysphagia in children and is commonly treated with esophageal balloon dilation. However, surgery may be required if the stenosis does not respond to dilation. Although esophageal actinomycosis can cause severe esophageal strictures and be refractory to balloon dilation, it has been reported to respond effectively to antimicrobial therapy in adults. However, the course of the disease and appropriate treatment strategies in children are not well understood. We present a case of a previously healthy 2-year-old boy diagnosed with esophageal stenosis because of actinomycosis. The patient was treated with intravenous penicillin G, followed by oral amoxicillin for 8 weeks and 6 months, respectively. After completion of the antimicrobial treatment, the patient showed improvement in symptoms and endoscopic findings. At the 1-year follow-up, the patient showed consistent weight gain and normal growth without further intervention. This case highlights the importance of considering esophageal actinomycosis as a potential cause of esophageal stenosis in children and the potential effectiveness of antimicrobial therapy in avoiding surgical intervention.

Inflammation-Induced Attenuation of Prostaglandin D2 Elimination across Rat Blood-Brain Barrier: Involvement of the Downregulation of Organic Anion Transporter 3 and Multidrug Resistance-Associated Protein 4.

Prostaglandin (PG) D2 is a lipid mediator, and in the brain, overproduction of PGD2 is reportedly involved in the progression and exacerbation of neuroinflammation. The objective of this study was to elucidate PGD2 efflux transport, under normal and inflammatory conditions, across the blood-brain barrier (BBB), which is formed by brain capillaries. Elimination of [3H]PGD2 across the BBB of normal and lipopolysaccharide (LPS)-induced inflammatory rats was examined by the intracerebral microinjection technique. After intracerebral injection, the percentage of [3H]PGD2 remaining in the ipsilateral cerebrum decreased with time, with a half-life of 13 min. This [3H]PGD2 elimination across the BBB was significantly inhibited by the co-administration of unlabeled PGD2, which suggests carrier-mediated PGD2 efflux transport at the BBB. In isolated rat brain capillaries, mRNA expression of organic anion transporter (Oat) 3, organic anion-transporting polypeptide (Oatp) 1a4, and multidrug resistance-associated protein (Mrp) 4 was observed. In addition, co-administration of substrates/inhibitors for Oat3, Oatp1a4, and/or Mrp4, such as benzylpenicillin and cefmetazole, reduced [3H]PGD2 elimination across the BBB. Data suggest that Oat3 and Mrp4, but not Oatp1a4 are involved in PGD2 elimination across the BBB, as Oatp1a4-expressing Xenopus (X.) oocytes did not show the significant [3H]PGD2 uptake compared with water-injected X. oocytes. In LPS-treated rats, [3H]PGD2 elimination across the BBB and mRNA expression levels of Oat3 and Mrp4 were significantly decreased. Our data suggest that Oat3- and Mrp4-mediated PGD2 elimination across the BBB is attenuated under inflammatory conditions.

More than meets the eye: Papilledema from syphilis posing as idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH), or pseudotumor cerebri, is a diagnosis of exclusion. Elevated intracranial pressure (ICP) can result from a variety of inflammatory and structural causes affecting cerebrospinal fluid production and absorption. First described in 1935, syphilis is a well-established cause of elevated ICP, referred to as syphilitic hydrocephalus. We report a case of a 49-year-old man presenting with vision changes and headache who was treated for IIH without resolution of symptoms, and eventually diagnosed with syphilitic hydrocephalus. Syphilis should be considered as a cause of elevated ICP prior to a diagnosis of IIH.

Recognizing and limiting syphilis to prevent congenital syphilis.

Syphilis is on the rise in every age and ethnicity group across the United States. The rate of congenital syphilis has started to rise as well, increasing the need for syphilis screening before pregnancy occurs. Raising awareness for syphilis screening, especially among sexually active women, is important, as the implications of this disease have lifelong effects for mother and child.

Syphilitic chorioretinitis presenting as a choroidal granuloma.

A rare case of syphilitic uveitis presenting as a choroidal granuloma is described in this case report. The clinical picture resembled that of a tubercular choroidal granuloma. However, the patient was positive for treponemal (treponema pallidum hemagglutination assay) as well as non-treponemal tests (venereal disease research laboratory test) for syphilis. Therefore, the patient was treated for ocular syphilis and responded to antisyphilitic therapy. There was a complete resolution of the lesion at the end of 14 days of treatment.

Exploring Penicillin G as an Intrawound Antibiotic Powder for Prevention of Postoperative Shoulder Infections: Does It Exhibit In Vitro Chondrotoxicity?

Cutibacterium acnes (C. acnes) is a significant insidious pathogen for postoperative infections in shoulder surgery. Studies have demonstrated that certain topical antibiotic powders used have the potential for chondrotoxicity. Benzylpenicillin, commonly referred to as Penicillin G (Pen G) has the lowest minimum inhibitory concentration (MIC) for C. acnes. There is no research regarding the topical application of Pen G during shoulder surgery, nor has its chondrocyte toxicity been previously investigated. This study sought to characterize the in vitro chondrocyte toxicity of Pen G. Culture-derived bovine chondrocytes were exposed to serial Pen G concentrations and compared with a positive and negative control. A negative control of growth medium and positive control of 1% Triton solution. The chondrocyte viability was assessed via spectrophotometer absorbance. The treatment groups were analyzed using one-way repeated measures analysis of variance and Pearson's correlation analysis. The chondrocyte viability was significantly higher for all Pen G concentrations as compared with the positive control (p < 0.001). All concentrations of Pen G exhibited continued chondrocyte metabolic activity over time. Analysis of variance, independent of time, demonstrated no significant decrease in chondrocyte viability for Pen G concentrations ≤6.25 mg/ml, as compared with the negative control (p > 0.05). Pen G demonstrated a significant negative correlation with its concentration and absorbance (r = 0.371, p < 0.001), however, concentrations ≤6.25 mg/ml did not demonstrate a significant decrease in chondrocyte viability (p = 0.063). Pen G in concentrations appropriate for C. acnes is not significantly chondrotoxic and may be safe for intrawound application. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:726-730, 2020.

Atypical development of neurosyphilis mimicking limbic encephalitis.

A previously healthy 35-year-old man suffering from behavioral and mental deterioration for three months was referred to our facility. On admission, the patient was dysphasic and had tonic-clonic seizures. Neurological examination showed mental confusion, euphoric mood, mania, paranoia, and mild motor dysphasia. Magnetic resonance imaging (MRI) was performed twice but no abnormalities were revealed. His acute confusional state, elevated cerebrospinal fluid (CSF) protein, epileptic seizure and electroencephalogram showing intermittent frontal slowness were all suggestive of encephalitis. The patient was treated with acyclovir without significant improvement in his condition. Testing for herpes simplex virus and human immunodeficiency virus was negative. Limbic encephalitis was suspected and the patient was treated with intravenous immunoglobulin (IVIG) for five days. Venereal disease research laboratory and Treponema pallidum hemagglutination assay were both tested positive in serum and CSF. Neurosyphilis was diagnosed, and the patient received a 14-day course of penicillin G with gradual improvement. Anti-N-methyl-D-aspartate-receptor (anti-NMDAR) antibodies were positive in serum, confirming the presence of encephalitis. The atypical clinical presentation of neurosyphilis with symptomatology mimicking encephalitis and no MRI abnormalities made the diagnosis challenging. Coexistence of neurosyphilis with anti-NMDAR encephalitis has been reported only in one recent study. Our case demonstrates the importance of testing for syphilis in patients with unexplained neurologic deficits and suspected encephalitis.

False-positive elevation of 1,3-beta-D-glucan caused by continuous administration of penicillin G.

The 1,3-beta-D-Glucan (BDG) assay is widely used for the diagnosis of fungal infections, especially in patients with hematologic malignancies. Some antimicrobials have been reported to cause false-positive results for BDG, but there has been no report on the effect of penicillin G (PCG) on BDG levels. We experienced a patient who developed false-positive BDG elevation during the administration of PCG for osteomyelitis due to Streptococcus pneumoniae infection. The serum BDG level increased up to 81.0 pg/ml during the continuous administration of PCG at 24 million units per day. However, chest and paranasal CT scan showed no evidence of fungal infection. The BDG level decreased to 38.0 pg/ml at 14 hours after the discontinuation of PCG. The amount of BDG in one vial of PCG inferred from these serum BDG levels is very similar to the actual BDG concentration in a vial of PCG. Therefore, during the administration of PCG, elevated BDG levels should be interpreted with caution, as they may be false-positive results.

Treatment of Syphilis-Associated Cerebral Vasculitis: Reappearance of an Old Question.

BACKGROUND: Cerebral vasculitis caused by neurosyphilis is a re-emerging problem with diagnostic and treatment issues, especially for human immunodeficiency virus patients. METHODS: We present a case of relapsing syphilis-associated cerebral vasculitis, despite the recommended first-line antibiotic treatment, that was successfully treated with a second intravenous penicillin G course and corticosteroids. RESULTS: A 50-year old man went to the emergency department for bilateral episodes of red and painful eyes with progressive but severe visual acuity loss. He was diagnosed with bilateral panuveitis and neurosyphilis favored by an unknown human immunodeficiency virus infection with a CD4 count of 236 mm3. Despite appropriate and well-conducted treatment including intravenous penicillin G, short-term corticosteroid, and highly active antiretroviral therapy, a symptomatic relapse of the syphilis-associated cerebral vasculitis occurred. After a second course of penicillin and corticosteroids, he made a complete recovery. CONCLUSIONS: Neurosyphilis and human immunodeficiency virus co-infection is a reappearing challenging situation that should be considered with care by physicians because recommended antibiotic treatment sometimes fails. Corticosteroid therapy should be discussed in case of cerebral vasculitis.

Secondary pulmonary syphilis: Case report and review of literature.

INTRODUCTION: Syphilis is a sexually transmitted disease that can affect numerous organs in its secondary or tertiary stages. We describe a case of secondary syphilis with pulmonary involvement and we present a literature review. PATIENTS AND METHODS: A 69-year-old male patient was admitted to hospital for dyspnoea and extended papular exanthema with palmoplantar involvement. The serological test for syphilis was positive. Ocular examination showed bilateral papillitis and retinal haemorrhage. Chest radiography revealed an interstitial alveolar infiltrate predominantly in the upper lobes, mild pleural effusion and hilar adenopathy. These infiltrates were slightly hypermetabolic on PET scan suggesting inflammatory or infectious origin. Treatment with intravenous penicillin G was effective on cutaneous, ocular and pulmonary manifestations. DISCUSSION: Lung involvement in secondary syphilis is poorly known and rarely described. We found 27 cases of pulmonary syphilis reported in English and the main European languages since 1967. Mean age at diagnosis was 46 years with clear male predominance (89%). HIV co-infection was declared in 5 cases. Treponema pallidum was found in 6 patients using PCR on bronchoalveolar lavage (BAL) (3 patients) or on a lung biopsy (1 patient), immunohistochemistry (IHC) on BAL (1 patient) and Giemsa staining on a pleural fluid sample (1 patient). Chest X-rays may show unilateral or bilateral infiltrates or nodules with or without pleural effusion or hilar adenopathy. Sub-pleural involvement is frequent and penicillin is the treatment of choice. CONCLUSION: Pulmonary syphilitic involvement should be suspected where pulmonary symptoms or radiological changes occur in secondary syphilis. IHC, special staining or PCR on BAL, pleural fluid or lung tissue are useful for the identification of spirochetes.

Lesson of the month 1: Lemierre's syndrome: a reminder of the 'forgotten disease'.

Lemierre's syndrome is a condition characterised by suppurative thrombophlebitis of the internal jugular (IJ) vein following a recent oropharyngeal infection, with resulting septicaemia and metastatic lesions. It is strongly associated with Fusobacterium necrophorum, a Gram-negative bacilli. Key to early diagnosis is awareness of the classical history and course of this illness, and therefore to ask about a history of recent oropharyngeal infections when a young patient presents with fever and rigors. Diagnosis can be confirmed by showing thrombophlebitis of the IJ vein, culturing F necrophorum from normally sterile sites or demonstrating metastatic lesions in this clinical setting. The cornerstone of management is draining of purulent collection where possible and prolonged courses of appropriate antibiotics. In this article, we review a case study of a young man with Lemierre's syndrome and discuss the condition in more detail.

Modified tunicamycins with reduced eukaryotic toxicity that enhance the antibacterial activity of ß-lactams.

Tunicamycins (TUN) are inhibitors of the UDP-HexNAc: polyprenol-P HexNAc-1-P transferase family of enzymes, which initiate the biosynthesis of bacterial peptidoglycan and catalyze the first step in eukaryotic protein N-glycosylation. The TUN are therefore general and potent toxins to both eukaryotes and prokaryotes. Screening a library of synthetic TUN against Bacillus and yeast identified TUN that are antibacterial, but have significantly reduced eukaryotic toxicity. One of these (Tun-15:0) differs from the native TUN control only by the lack of the conjugated double bond in the tunicaminyl N-acyl group. Tun-15:0 also showed reduced inhibition for protein N-glycosylation in a Pichia-based bioassay. Natural TUN was subsequently modified by chemically reducing the N-acyl double bond (TunR1) or both the N-acyl and uridyl double bonds (TunR2). TunR1 and TunR2 retain their antibacterial activity, but with considerably reduced eukaryotic toxicity. In protein N-glycosylation bioassays, TunR1 is a less potent inhibitor than native TUN and TunR2 is entirely inactive. Importantly, the less toxic TunR1 and TunR2 both enhance the antibacterial activity of ß-lactams: oxacillin by 32- to 64-fold, comparable with native TUN, and with similar enhancements for methicillin and penicillin G. Hence, the modified TUNs, TunR1 and TunR2, are potentially important as less-toxic synergistic enhancers of the ß-lactams.

Treatment of chronic sinusitis in a horse with systemic and intra-sinus antimicrobials.

A 12-year-old Norwegian Fjord gelding was diagnosed with paranasal sinusitis as a post-operative complication of tooth repulsion surgery. The infection with inspissated purulent material persisted despite sinus trephination and lavage, and systemic antimicrobial therapy. Resolution occurred following infusion of a gelatin/penicillin mixture into the right rostral and caudal maxillary sinus.

Traitement de la sinusite chronique chez un cheval à l'aide d'antimicrobiens systémiques et dans les sinus. Une sinusite paranasale a été diagnostiquée chez un hongre Fjord âgé de 12 ans comme complication postopératoire d'une chirurgie pour la répulsion d'une dent. L'infection avec du matériel purulent épaissi a persisté malgré la trépanation et le lavage du sinus et une thérapie antimicrobienne systémique. La résorption s'est produite après l'infusion d'un mélange de gélatine et de pénicilline dans les sinus maxillaires rostral et caudal droits.(Traduit par Isabelle Vallières).

Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

BACKGROUND: Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai. METHODOLOGY/PRINCIPAL FINDINGS: Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13%) and 0.35% (95% CI: 0.06-1.39%), respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients), fatigue (2 patients), cough (1 patient), sore throat (1 patient), diarrhea (1 patient) and erythematous rash (1 patient). The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05). Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia. CONCLUSIONS/SIGNIFICANCE: Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for patients in good physical condition after withdrawing anti-neurosyphilis regimen. We did not see an exacerbation of neutropenia in patients with the readministration of benzylpenicillin.

Unusual Behavior of a Posttraumatic Scar: Craniofacial Actinomycosis.

Actinomycosis is a chronic suppurative granulomatous infection most commonly involving the cervicofacial region. Clinical diagnosis is usually difficult, and fine-needle aspiration cytology or imaging studies are usually unhelpful in diagnosing actinomycosis. Definitive diagnosis is based on the histopathological examination of a tissue biopsy. The authors report a case of a 32-year-old healthy man who underwent multiple surgeries over a period of 7 years to correct a posttraumatic scar on his forehead with unusual behavior. Final diagnosis was made by tissue biopsy. Scar was excised and penicillin was administered for 1 month postoperatively; after a 12-month follow-up, the wound was fully healed with minimal scarring and no recurrence.

Benzylpenicillin plus an aminoglycoside versus meropenem in neutropenic lymphoma and leukaemia patients with a suspected bacterial infection: a randomized, controlled trial.

OBJECTIVES: In Norway, initial treatment of febrile neutropenia (FN) has traditionally been benzylpenicillin plus an aminoglycoside. Internationally, FN is often treated with a broad-spectrum ß-lactam antibiotic. We aimed to compare these two regimens in a prospective, randomized, trial in patients with lymphoma or leukaemia with an expected period of neutropenia ≥7 days, and a suspected bacterial infection. METHODS: Adult neutropenic patients with lymphoma or leukaemia, and a suspected bacterial infection, were randomized for treatment with benzylpenicillin plus an aminoglycoside or meropenem. The primary endpoint was clinical success, defined as no modification of antibiotics and clinical stability 72 h after randomization. RESULTS: Among 322 randomized patients, 297 proved evaluable for analyses. Fifty-nine per cent (95% CI 51%-66%), (87/148) of the patients given benzylpenicillin plus an aminoglycoside were clinically stable, and had no antibiotic modifications 72 h after randomization, compared with 82% (95% CI 75%-87%), (122/149) of the patients given meropenem (p <0.001). When the antibiotic therapy was stopped, 24% (95% CI 18%-32%), (36/148) of the patients given benzylpenicillin plus an aminoglycoside, compared with 52% (95% CI 44%-60%), (78/149) of the patients given meropenem, had no modifications of their regimens (p <0.001). In the benzylpenicillin plus an aminoglycoside arm, the all-cause fatality within 30 days of randomization was 3.4% (95% CI 1.2%-7.9%), (5/148) of the patients, compared with 0% (95% CI 0.0%-3.0%), (0/149) of the patients in the meropenem arm (p 0.03). CONCLUSION: Clinical success was more common in FN patients randomized to meropenem compared with the patients randomized to benzylpenicillin plus an aminoglycoside. The all-cause fatality was higher among the patients given benzylpenicillin plus an aminoglycoside.

A case of ileocecal actinomycosis treated by preoperative antibiotic treatment to reduce mass size followed by surgical resection.

A 65-year-old woman presented to a nearby clinic with a painful mass in the right lower abdominal region. She was suspected of having an appendiceal tumor on abdominal computed tomography (CT) and was referred to our hospital for surgery. Blood testing revealed increased inflammatory markers. Contrast-enhanced abdominal CT revealed a mass with poorly defined margins in the ileocecal region, which was adjacent to the external iliac vessels. A barium enema revealed unilateral wall deformities in the cecum through to the terminal ileum, whereas lower gastrointestinal endoscopy showed no clear epithelial tumor component. The patient was clinically diagnosed with ileocecal actinomycosis and treated with high-dose penicillin G. On day 15 of treatment, contrast-enhanced abdominal CT showed a reduction in mass size. On day 26, right hemicolectomy (D3) with combined resection of the external iliac vein (which could not be separated from the mass) was performed. Pathological examination revealed granulation tissue with granules of actinomyces, with filamentous bacteria detected by Grocott staining. With no evidence of malignancy, the final diagnosis of ileocecal actinomycosis was made. This report presents a case of clinically suspected ileocecal actinomycosis treated by preoperative antibiotic treatment to reduce mass size, followed by surgical resection.