Invasive Pyogenic Infections Research Articles

Cavernous Sinus Thrombosis Secondary to Streptococcus Constellatus Pharynges

Streptococcus constellatus pharyngis is a gram-positive commensal bacterium commonly found in the oropharynx, gastrointestinal and urogenital tracts. It might be an aggressive opportunistic pathogen causing invasive pyogenic infections in sterile areas, mostly as peritonsillar and orofacial abscesses. We report the case of a 6-year-old girl, who presented multiple head and neck abscesses and bilateral cavernous sinus thrombosis secondary to Streptococcus constellatus pharyngis. Cavernous sinus thrombosis, consequent to this microorganism, has not been reported to date in the literature. Due to the invasive features of this pathogen, a long-term antibiotherapy (up to 9 months) is required. Additionally, a surgical drainage is indicated in case of head and neck, or brain abscesses, larger than 20 or 25 mm respectively. Anticoagulation should be considered in case of venous thrombosis. The interest of this case is not only based on the rarity and severity of the disease, but also on the success of medical and surgical therapy (including long- term antibiotics, anticoagulation and two surgical procedures). This experience may serve as a guide to treat future cases.

An unexpected pathogen causing multiple intra-abdominal abscesses in an immunocompetent patient

Streptococcus constellatus is a member of the group now called Streptococcus anginosus. This microorganism is part of the normal oropharyngeal, gastrointestinal and genitourinary microbiota. However, it may cause serious infections such as pharyngitis, bacteremia and invasive pyogenic infections in immunocompromised patients. We report the first case in Colombia of an adult male with no relevant medical history and with an unusual presentation of infection by S. constellatus and whose laboratory results showed an important systemic inflammatory response and radiographic evidence of abdominal involvement with poor response to medical and surgical management. Since there are few reports in international medical journals about intra-abdominal infection by S. constellatus and taking into consideration the need of a multidisciplinary intervention, this report may be of interest for both clinical and surgical practitioners.

IRAK4 Deficiency Presenting with Anti-NMDAR Encephalitis and HHV6 Reactivation

IRAK4 deficiency is an inborn error of immunity predisposing patients to invasive pyogenic infections. Currently, there is no established simple assay that enables precise characterization of IRAK4 mutant alleles in isolation. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune condition that is characterized by psychiatric symptoms, involuntary movement, seizures, autonomic dysfunction, and central hypoventilation. It typically occurs in adult females associated with tumors. Only a few infantile cases with anti-NMDAR encephalitis have been so far reported. We identified a 10-month-old boy with IRAK4 deficiency presenting with anti-NMDAR encephalitis and human herpes virus 6 (HHV6) reactivation. The diagnosis of IRAK4 deficiency was confirmed by the identification of compound heterozygous mutations c.29_30delAT (p.Y10Cfs*9) and c.35G>C (p.R12P) in the IRAK4 gene, low levels of IRAK4 protein expression in peripheral blood, and defective fibroblastic cell responses to TLR and IL-1 (TIR) agonist. We established a novel NF-κB reporter assay using IRAK4-null HEK293T, which enabled the precise evaluation of IRAK4 mutations. Using this system, we confirmed that both novel mutations identified in the patient are deleterious. Our study provides a new simple and reliable method to analyze IRAK4 mutant alleles. It also suggests the possible link between inborn errors of immunity and early onset anti-NMDAR encephalitis.

Streptococcus anginosus Empyema Induced by Dental Abscess: A Case Report

Streptococcus anginosus is a gram-positive catalase-negative cocci and commensal flora of the oropharynx and gastrointestinal tract. Streptococcus anginosus is known to be highly virulent and known to cause invasive pyogenic infection which may necessitate emergent surgical treatment. We present a case of a 53-year-old female with dental caries and uncontrolled diabetes mellitus who presented with progressive shortness of breath for 1 week. A computed tomography scan of the chest showed a loculated empyema which was treated with emergent video-assisted thoracoscopic surgery. Pleural fluid culture as well as sputum cultures grew Streptococcus anginosus . The patient was treated intravenous cephalosporins and discharged on oral antibiotics after 14 days with outpatient dental follow-up and improvement of symptoms. J Med Cases. 2020;11(9):289-291 doi: https://doi.org/10.14740/jmc3547

Invasive pyogenic infection and infective endocarditis due to Streptococcus anginosus

Rationale:Streptococcus anginosus mostly colonizes the digestive and genitourinary system, including the oropharyngeal region. It commonly causes invasive pyogenic infection, but less likely causes infective endocarditis (IE).Patient concerns:An 18-year-old woman who had an underlying mitral valve prolapse without mitral regurgitation presented to our hospital with low-grade fever, left leg weakness, and left abdominal pain. She was diagnosed with brain infarction and microabscess as well as IE. The patient totally recovered after the 6-week course of intravenous antibiotics.Diagnosis:Brain magnetic resonance imaging revealed brain infarction and microabscess. Abdominal computed tomography revealed splenic and left renal infarction. Three sets of blood culture were positive for S anginosus. Transthoracic echocardiogram identified mitral valve prolapse with moderate eccentric mitral valve regurgitation, and a 0.3 × 0.6-cm vegetation was found on the left mitral valve. All of these results meet the modified Duke criteria.Interventions:The abdominal pain and left leg weakness were improving after 2 weeks of intravenous antibiotics treatment. No neurological sequelae were noted after completing the 6-week course of medical treatment.Outcomes:The patient was successfully treated and discharged after completing the 6-week intravenous antibiotics treatment.Lessons:IE should be considered in young patients with native valve disease who have prolonged fever. Though S anginosus commonly causes invasive pyogenic infection, patients with native valve disease should be checked for IE.

Machine Learning Analyses on Data including Essential Oil Chemical Composition and In Vitro Experimental Antibiofilm Activities against Staphylococcus Species.

Biofilm resistance to antimicrobials is a complex phenomenon, driven not only by genetic mutation induced resistance, but also by means of increased microbial cell density that supports horizontal gene transfer across cells. The prevention of biofilm formation and the treatment of existing biofilms is currently a difficult challenge; therefore, the discovery of new multi-targeted or combinatorial therapies is growing. The development of anti-biofilm agents is considered of major interest and represents a key strategy as non-biocidal molecules are highly valuable to avoid the rapid appearance of escape mutants. Among bacteria, staphylococci are predominant causes of biofilm-associated infections. Staphylococci, especially Staphylococcus aureus (S. aureus) is an extraordinarily versatile pathogen that can survive in hostile environmental conditions, colonize mucous membranes and skin, and can cause severe, non-purulent, toxin-mediated diseases or invasive pyogenic infections in humans. Staphylococcus epidermidis (S. epidermidis) has also emerged as an important opportunistic pathogen in infections associated with medical devices (such as urinary and intravascular catheters, orthopaedic implants, etc.), causing approximately from 30% to 43% of joint prosthesis infections. The scientific community is continuously looking for new agents endowed of anti-biofilm capabilities to fight S. aureus and S epidermidis infections. Interestingly, several reports indicated in vitro efficacy of non-biocidal essential oils (EOs) as promising treatment to reduce bacterial biofilm production and prevent the inducing of drug resistance. In this report were analyzed 89 EOs with the objective of investigating their ability to modulate bacterial biofilm production of different S. aureus and S. epidermidis strains. Results showed the assayed EOs to modulated the biofilm production with unpredictable results for each strain. In particular, many EOs acted mainly as biofilm inhibitors in the case of S. epidermidis strains, while for S. aureus strains, EOs induced either no effect or stimulate biofilm production. In order to elucidate the obtained experimental results, machine learning (ML) algorithms were applied to the EOs’ chemical compositions and the determined associated anti-biofilm potencies. Statistically robust ML models were developed, and their analysis in term of feature importance and partial dependence plots led to indicating those chemical components mainly responsible for biofilm production, inhibition or stimulation for each studied strain, respectively.

Streptococcus anginosus Infections: Crossing Tissue Planes

Streptococcus anginosus has long been recognized to cause invasive pyogenic infections. This holds true for thoracic infections where S anginosus has a propensity for abscess and empyema formation. Early diagnosis is important given the significant morbidity and mortality associated with thoracic S anginosus infections. Yet, distinguishing thoracic S anginosus clinically is difficult. We present three cases of thoracic S anginosus that demonstrated radiographic extension across tissue planes, including the interlobar fissure, diaphragm, and chest wall. Few infectious etiologies are known to cross tissue planes. Accordingly, we propose S anginosus be considered among the differential diagnosis of potential infectious etiologies causing radiographic extension across tissue planes.

Pyrosequencing reveals the complex polymicrobial nature of invasive pyogenic infections: microbial constituents of empyema, liver abscess, and intracerebral abscess

The polymicrobial nature of invasive pyogenic infections may be underestimated by routine culture practices, due to the fastidious nature of many organisms and the loss of viability during transport or from prior antibacterials. Pyrosequencing was performed on brain and liver abscesses and pleural fluid and compared to routine culture data. Forty-seven invasive pyogenic infection samples from 44 patients [6 intracerebral abscess (ICA), 21 pyogenic liver abscess (PLA), and 18 pleural fluid (PF) samples] were assayed. Pyrosequencing identified an etiologic microorganism in 100% of samples versus 45% by culture, p <0.01. Pyrosequencing was also more likely than traditional cultures to classify infections as polymicrobial, 91% versus 17%, p <0.001. The median number of genera identified by pyrosequencing compared to culture was 1 [interquartile range (IQR) 1-3] versus 0 (IQR 0-1) for ICA, 7 (IQR 1-15) versus 1 (IQR 0-1) for PLA, and 15 (IQR 9-19) versus 0 (IQR 0-1) for PF. Where organisms were cultured, they typically represented the numerically dominant species identified by pyrosequencing. Complex microbial communities are involved in invasive pyogenic infection of the lung, liver, and brain. Defining the polymicrobial nature of invasive pyogenic infections is the first step towards appreciating the clinical and diagnostic implications of these complex communities.

If You See Me, Look Deeper

If you see me, look deeper. Streptococcus constellatus is a member of the Streptococcus anginosus group, with a known propensity for invasive pyogenic infections, and as this association is well known, one should always look for occult pyogenic or suppurative collections in a patient with S. constellatus bacteremia. A 62-year-old diabetic man with history of traumatic brain injury and dementia was admitted to the hospital with a fever (104°F), tachypnea, and leukocytosis and normal liver function test results were found to have S. constellatus bacteremia. As the nature of this organism is known, although he had no localizing foci of infection and was asymptomatic with normal liver function test results, further workup was done which revealed occult abscesses in his gall bladder.

Susceptibility of 170 isolates of the USA300 clone of MRSA to macrolides, clindamycin and the novel ketolide cethromycin

Sir, Historically, methicillin-resistant Staphylococcus aureus (MRSA) has been regarded as a nosocomial pathogen responsible for severe toxin-mediated disease or invasive pyogenic infections. In recent years, however, community-associated MRSA (CA-MRSA) has been reported from around the world. Although the first CA-MRSA strains were susceptible to most antimicrobials, antimicrobial resistance has increased. One CA-MRSA clone, identified by the CDC as pulsotype USA300, has been implicated in outbreaks within the USA and is resistant to many currently marketed antimicrobial agents. This clone carries both the SCCmec IV element and the Panton–Valentine leukocidin (PVL) locus. The aim of this study was to compare the activity of a novel ketolide, cethromycin (previously ABT-773), with potentially improved pharmacodynamic and therapeutic benefits, three other macrolides (azithromycin, clarithromycin and erythromycin) and one lincosamide (clindamycin) against the 170 MRSA USA300 isolates that are in the Center for Biological Defense (CBD) collection. Seventeen MRSA isolates were procured from two hospital laboratories in Seattle, WA, USA. These were isolated from cultures of blood, skin lesions and tissue abscesses of patients seen in their clinics or emergency department in 2003 and 2004. Of the remaining 153 MRSA, 121 isolates were obtained from cultures of lesions, abscesses and nasopharyngeal specimens from outpatients seen at west central Florida clinical laboratories and doctor’s offices, whereas 32 MRSA were isolated from lesions, abscesses, nasopharyngeal and blood specimens acquired from patients seen at hospitals in the Tampa Bay area from 2004 to 2006. These isolates were previously characterized as USA300 by PFGE using Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA) standards for comparison. Cethromycin (obtained from Advanced Life Sciences, Woodridge, IL, USA) was prepared and diluted with calciumadjusted Mueller–Hinton broth (Remel, Lenexa, KS, USA) using 96-well microtitre plates following standard protocols. The MIC and MBC were determined using orthodox procedures. Clarithromycin, erythromycin and clindamycin were tested with Sensititre by TREK Diagnostic Systems (Cleveland, OH, USA), whereas azithromycin, erythromycin and clindamycin were tested using Etest (AB Biodisk, North America Inc., Piscataway, NJ, USA), according to manufacturer’s instructions. All MIC interpretations followed CLSI guidelines. Clindamycin resistance was examined further with the D-test. Controls were S. aureus ATCC 29213, S. aureus ATCC BAA977 and S. aureus ATCC BAA976. Cethromycin was effective against all 170 isolates (Table 1). The cethromycin MIC range was 0.002–0.125 mg/L, whereas the MIC50 and MIC90 were both 0.002 mg/L. The cethromycin MBC range was 0.002–1.0 mg/L, with the MBC50 of 0.002 mg/L and the MBC90 of 0.008 mg/L. Of the 170 CA-MRSA, 169 (99.4%) were intermediate or resistant to at least one macrolide. In contrast, 164 (96.5%) isolates were susceptible to clindamycin. Only six (3.5%) isolates demonstrated either constitutive resistance [4 (2.4%)] or inducible resistance [2 (1.2%)] to clindamycin. This is unlike the USA300 isolates in Boston where 57% of the isolates were clindamycin-resistant. Against 10 erythromycin-susceptible isolates, the cethromycin MIC and MBC ranges were 0.002–0.008 mg/L, compared with the MIC range of 0.002–0.25 mg/L and MBC range of 0.002–1.0 mg/L obtained with the erythromycin-resistant isolates. However, MIC50 and MBC50 values, as well as MIC90 and MBC90 values, did not change regardless of erythromycin susceptibility. There were six isolates resistant to both erythromycin and clindamycin, against which cethromycin MIC and MBC ranges were 0.002–0.06 mg/L. This population’s susceptibility to cethromycin is especially important in the light of the fact that most isolates were resistant to one or more macrolides. This collection of MRSA USA300 isolates was overwhelmingly macrolide-resistant and clindamycinsusceptible. The study of Chavez-Bueno et al. demonstrated a similar pattern in CA-MRSA isolates among children in Texas where the inducible resistance to clindamycin was slowly replaced by clindamycin susceptibility (non-inducible resistance). Most of the CA-MRSA isolates in the Texas study carried the erm(C) gene, with others carried erm(A) or msr(A) with or without erm(C). This phenotypic change suggests an alteration in the proportion of the macrolide resistance determinants in the population. Tenover et al. reported the msr(A) gene in isolates comprising a specific clone (USA300-0114). Accordingly, we hypothesized that most of the CBD collection of MRSA USA300 isolates (only one being USA300-0114) also carried a different determinant, putatively the msr(A)/msr(B) gene encoding an efflux protein that normally renders a bacterial cell resistant only to macrolides and streptogramin B compounds (MS phenotype) instead of the MLSB resistance genes [i.e. erm(A) and erm(C)]. Using the oligonucleotides described by Sutcliffe et al. for PCR primers and a well-characterized MRSA strain NARSA 384 (USA300-0114) as positive control, we performed a PCR assay for the msr(A) gene on DNA extracted from all 170 isolates. After the amplicons were electrophoresed on a 1% agarose gel, a positive PCR reaction yielded a DNA band of 399 bp. All negative and questionable results were performed three times. The assay produced a positive reaction in 160 (94.1%) isolates, whereas only 10 (5.9%) of the 170 MRSA yielded negative PCR reactions. These Research letters

Brainstem Infarcts as an Early Manifestation of &lt;I&gt;Streptococcus&lt;/I&gt; &lt;I&gt;anginosus&lt;/I&gt; Meningitis

Vasculitis and infarcts are well-established sequelae of bacterial meningitis. However, early large-vessel involvement is rare, particularly within the brainstem. There has been one previous case report of a young male who presented with pontine infarct as an early manifestation of Streptococcus milleri meningitis. We present another case of brainstem infarction associated with meningitis caused by Streptococcus anginosus. We report a 58-year-old man who developed constitutional symptoms and gait instability, followed by progressive stupor. On examination, he had a Glasgow Coma Scale of 8 with intact brainstem reflexes and no focal findings. Magnetic resonance imaging documented bilateral pontine infarcts. S. anginosus was isolated from cerebrospinal fluid. Despite proper antibiotic treatment, the patient remained comatose and care was withdrawn. Postmortem examination revealed the meningitis was predominantly localized at the base of the brain. In addition, ventriculitis, multiple abscesses, and multiple infarcts in the pons and midbrain were found. S. anginosus, which is part of the normal human flora, causes invasive pyogenic infections and is an uncommon cause of bacterial meningitis. This type of infection is mostly situated at the base of the brain and has a propensity to encase the basilar artery and its perforators, thus causing brainstem stroke early in its course.