Helicobacter cinaedi Bacteremia in Children: A Case Report and Literature Review.

Helicobacter cinaedi is known to cause invasive infections in immunocompromised adults. Here we report the first case of H. cinaedi bacteremia in a child with nephrotic syndrome. The patient presented with a mild transient febrile illness that resolved spontaneously. We discuss the diagnostic challenges associated with this case and the microbiologic approach, including genomic analysis. Furthermore, we review the current case together with all previous pediatric cases (n = 6). Notably, all cases involved neonates or otherwise immunocompromised individuals and were characterized by severe disease with complicated infections (eg, meningitis, cholangitis and arthritis). H. cinaedi bacteremia in children is associated with a wide spectrum of clinical presentations ranging from mild to life-threatening conditions. This bacterium may be difficult to diagnose and require specialized methods.

Metagenomic sequencing for investigation of a national keratoconjunctivitis outbreak, Israel, 2022.

BackgroundEpidemics of keratoconjunctivitis may involve various aetiological agents. Microsporidia are an uncommon difficult-to-diagnose cause of such outbreaks.AimDuring the third quarter of 2022, a keratoconjunctivitis outbreak was reported across Israel, related to common water exposure to the Sea of Galilee. We report a comprehensive diagnostic approach that identified Vittaforma corneae as the aetiology, serving as proof of concept for using real-time metagenomics for outbreak investigation.MethodsCorneal scraping samples from a clinical case were subjected to standard microbiological testing. Samples were tested by calcofluor white staining and metagenomic short-read sequencing. We analysed the metagenome for taxonomical assignment and isolation of metagenome-assembled genome (MAG). Targets for a novel PCR were identified, and the assay was applied to clinical and environmental samples and confirmed by long-read metagenomic sequencing.ResultsFluorescent microscopy was suggestive of microsporidiosis. The most abundant species (96.5%) on metagenomics analysis was V. corneae. Annotation of the MAG confirmed the species assignment. A unique PCR target in the microsporidian rRNA gene was identified and validated against the clinical sample. The assay and metagenomic sequencing confirmed V. corneae in an environmental sludge sample collected at the exposure site.ConclusionsThe real-time utilisation of metagenomics allowed species detection and development of diagnostic tools, which aided in outbreak source tracking and can be applied for future cases. Metagenomics allows a fully culture-independent investigation and is an important modality for public health microbiology.

Viral and Bacterial Respiratory Pathogens during the COVID-19 Pandemic in Israel.

BACKGROUND: previous worldwide reports indicated a substantial short-term reduction in various respiratory infections during the early phase of the SARS-CoV-2 pandemic. AIMS: exploring the long-term impact of the COVID-19 pandemic on respiratory pathogens. METHODS: retrospective analysis of bacterial and viral positivity rate in respiratory samples, between 1 January 2017-30 June 2022 in a tertiary hospital in Jerusalem, Israel. RESULTS: A decline in overall respiratory tests and positivity rate was observed in the first months of the pandemic. Respiratory isolations of Hemophilus influenza and Streptococcus pneumoniae were insignificantly affected and returned to their monthly average by November 2020, despite a parallel surge in COVID-19 activity, while Mycoplasma pneumoniae was almost eliminated from the respiratory pathogens scene. Each viral pathogen acted differently, with adenovirus affected only for few months. Human-metapneumovirus and respiratory-syncytial-virus had reduced activity for approximately a year, and influenza A virus resurged in November 2021 with the elimination of Influenza-B. CONCLUSIONS: After an immediate decline in non-SARS-CoV-2 respiratory infections, each pathogen has a different pattern during a 2-year follow-up. These patterns might be influenced by intrinsic factors of each pathogen and different risk reduction behaviors of the population. Since some of these measures will remain in the following years, we cannot predict the timing of return to pre-COVID-19 normalcy.

A Case Report of Mycoplasma hominis Subdural Empyema Following Decompressive Craniotomy, and a Review of Central Nervous System Mycoplasma hominis Infections.

Background: Mycoplasma hominis is a small cell-wall-free organism, part of the normal microbiota of the genitourinary tract. It is rarely involved in extragenital infections, mainly joint, surgical-site, and respiratory infections. Methods: We describe a case of M. hominis subdural empyema and lower limb surgical site infections, following decompressive craniotomy, after traumatic brain and extremities injury. In addition, a literature review of 34 cases M. hominis CNS infections was done. Results: Our case depicts a 25-years old patient who developed subdural empyema and surgical site infections in his cranium and fibula. Both sites were cultured, and small pinpoint colonies grew on blood agar. MALDI-TOF MS identified M. hominis. Simultaneously 16S-rDNA PCR from CSF detected M. hominis. Antimicrobial treatment was switched to doxycycline with improvement. Literature review revealed 21 adults and 13 pediatric cases of M. hominis CNS infection. Risk factors in adults were head trauma, neurosurgery, or post-partum period. Conclusions: Based upon the literature reviewed, we postulate that adult patients with head trauma or neurosurgical procedure, rarely are infected either through direct contamination during the trauma, or by undergoing urgent, urinary catheterization, and may experience distant infection due to translocation of M. hominis into the bloodstream. In such cases diagnosis is delayed due to difficulties in growing and identifying the bacteria. Empiric antimicrobials are usually not effective against mycoplasmas. These factors contributed to the mortality in adult cases (15%). Our rare case highlights the necessity of combining classical microbiology routines with advanced molecular techniques to establish a diagnosis in complicated cases.

A trespasser from a foreign land? A case report of primary mucosal leishmaniasis.

BACKGROUND: We report a clinically challenging and unusual case of L. donovani oral mucosal leishmaniasis. CASE PRESENTATION: Israeli resident with a former travel to central and North Africa, with no documented or prior cutaneous lesions presented with oral lesions of the maxillary gingiva and the upper lip. A delay in diagnosis and treatment have led to progression of the maxillary gingival lesions towards the hard palatal and the soft palate that could have potentially compromised the upper airway. CONCLUSIONS: This case highlights the importance of early diagnosis of leishmaniasis in patients with oral lesions and the laboratory workup necessary to appropriately characterize and treat the disease.

Therapeutic Potential of Injectable Nano-Mupirocin Liposomes for Infections Involving Multidrug-Resistant Bacteria.

Antibiotic resistance is a global health threat. There are a few antibiotics under development, and even fewer with new modes of action and no cross-resistance to established antibiotics. Accordingly, reformulation of old antibiotics to overcome resistance is attractive. Nano-mupirocin is a PEGylated nano-liposomal formulation of mupirocin, potentially enabling parenteral use in deep infections, as previously demonstrated in several animal models. Here, we describe extensive in vitro profiling of mupirocin and Nano-mupirocin and correlate the resulting MIC data with the pharmacokinetic profiles seen for Nano-mupirocin in a rat model. Nano-mupirocin showed no cross-resistance with other antibiotics and retained full activity against vancomycin-, daptomycin-, linezolid- and methicillin- resistant Staphylococcus aureus, against vancomycin-resistant Enterococcus faecium, and cephalosporin-resistant Neisseria gonorrhoeae. Following Nano-mupirocin injection to rats, plasma levels greatly exceeded relevant MICs for >24 h, and a biodistribution study in mice showed that mupirocin concentrations in vaginal secretions greatly exceeded the MIC90 for N. gonorrhoeae (0.03 µg/mL) for >24 h. In summary, Nano-mupirocin has excellent potential for treatment of several infection types involving multiresistant bacteria. It has the concomitant benefits from utilizing an established antibiotic and liposomes of the same size and lipid composition as Doxil®, an anticancer drug product now used for the treatment of over 700,000 patients globally.

Misidentification of Candida dubliniensis isolates with the VITEK MS.

The phylogenetic relatedness of Candida dubliniensis and C. albicans may lead to misidentification of C. dubliniensis and underestimation of its clinical significance. We evaluated the performance of VITEK-MS in identifying C. dubliniensis isolates following growth on different culture media. Correct identification was documented in 98% of the isolates grown on blood agar media whereas only 44% were correctly identified from SDA or CHROMagar. The use of non-manufacturer validated media for identifying C. dubliniensis with VITEK-MS, may result in misidentification of these isolates as C. albicans. This finding calls for reassessing the accuracy of fungal isolates identification in local workflows using non-validated culture media.

The Clinical Presentation of Pediatric Mycoplasma pneumoniae Infections-A Single Center Cohort.

BACKGROUND: Mycoplasma pneumoniae (MP) is a major cause of community-acquired upper and lower respiratory infections in school-age children; however, there is increasing recognition that younger children are also affected. Clinical manifestations vary from asymptomatic, to severe complicated pneumonia sometimes with extrapulmonary manifestations. METHODS: We reviewed the medical records of all MP positive pediatric patients admitted to the Hadassah-Hebrew University Medical Center. MP positive case was defined if MP polymerase chain reaction was positive from an oropharyngeal swab sent from 2007 to 2017. RESULTS: During the study period, we identified 353 MP positive pediatric cases, of which 51.3% (181 of 353) were younger than 6 years old. Full clinical data were available for 332 of 353 (94%). The median age was 5.7 years (range, 3 weeks to 18 years). Disease presentation differed between younger and older children. Children older than 6 years were more likely to have chest radiograph confirmed pneumonia (66% vs. 52%; P = 0.009), while younger children were more likely to have other respiratory manifestations (37% vs. 25%; P = 0.017). The duration of hospitalization and pediatric intensive care unit admission rate, however, did not differ between age groups. The rate of extrapulmonary manifestations were also similar. CONCLUSIONS: MP-associated infection is a significant cause of hospitalization in the pediatric population including younger children (<6 years old). However, the clinical presentation in younger age is less typical than is thought. These findings should prompt clinicians to consider MP infections also in children younger than 6 admitted with fever even without pneumonia.

Breast Implant Q Fever as a Source of In-Hospital Transmission.

Herein, we describe the first case of mammary implant infection caused by Coxiella burnetii, resulting in delayed diagnosis and treatment and an in-hospital cross-transmission of Q fever to medical personnel.

Multi-center evaluation of one commercial and 12 in-house real-time PCR assays for detection of Mycoplasma pneumoniae.

Detection of Mycoplasma pneumoniae by real-time PCR is not yet standardized across laboratories. We have implemented a standardization protocol to compare the performance of thirteen commercial and in-house approaches. Despite differences on threshold values of samples, all assays were able to detect at least 20M. pneumoniae genomes per reaction.

Streptococcal pyrogenic exotoxin G gene in blood and pharyngeal isolates of Streptococcus dysgalactiae subspecies equisimilis has a limited role in pathogenesis.

BACKGROUND: Streptococcus dysgalactiae subspecies equisimilis (SE) causes human infections that clinically resemble infections due to Streptococcus pyogenes (SP). SE expresses several virulence determinants initially identified in SP, including genes encoding streptococcal pyrogenic exotoxins. SE isolates from patients with toxic shock syndrome were found to harbor a gene designated spegg, which is similar to the SP pyrogenic exotoxin-G gene, termed speG. Other streptococcal pyrogenic exotoxins known to exist in SP were not detected. METHODS: To determine the prevalence of the superantigen gene, spegg, we examined 65 invasive SE from patients presenting from 1989 to 2008 with bacteremia secondary to a variety of illnesses including two patients who fulfilled the criteria for toxic shock syndrome, in comparison with 46 noninvasive pharyngeal isolates. All isolates were tested for the presence of spegg by polymerase chain reaction. Forty-four of the 65 blood isolates were also characterized by emm typing. RESULTS: spegg was identified in 49.2% and 69.5% of the blood and pharyngeal isolates, respectively. emm typing revealed the presence of 13 distinct types. There was no association between clinical presentation and the presence of spegg. We found an association between the presence of spegg and the emm type (p < 0.001). The emm types stG485 and stG840 were more frequent among spegg positive isolates, and stG4222, stG6, and stG166b were associated with spegg negative isolates. CONCLUSION: We found a high prevalence of spegg in invasive and noninvasive SE isolates, associated with specific emm types. Our finding suggests that this gene does not have a role in the pathogenesis of bacteremia.

Characterization of sil in invasive group A and G streptococci: antibodies against bacterial pheromone peptide SilCR result in severe infection.

Group G beta-hemolytic streptococcus (GGS) strains cause severe invasive infections, mostly in patients with comorbidities. GGS is known to possess virulence factors similar to those of its more virulent counterpart group A streptococcus (GAS). A streptococcal invasion locus, sil, was identified in GAS. sil encodes a competence-stimulating peptide named SilCR that activates bacterial quorum sensing and has the ability to attenuate virulence in GAS infections. We found that sil is present in most GGS strains (82%) but in only 25% of GAS strains, with a similar gene arrangement. GGS strains that contained sil expressed the SilCR peptide and secreted it into the growth medium. In a modified murine model of GGS soft tissue infection, GGS grown in the presence of SilCR caused a milder disease than GGS grown in the absence of SilCR. To further study the role of the peptide in bacterial virulence attenuation, we vaccinated mice with SilCR to produce specific anti-SilCR antibodies. Vaccinated mice developed a significantly more severe illness than nonvaccinated mice. Our results indicate that the sil locus is much more prevalent among the less virulent GGS strains than among GAS strains. GGS strains express and secrete SilCR, which has a role in attenuation of virulence in a murine model. We show that the SilCR peptide can protect mice from infection caused by GGS. Furthermore, vaccinated mice that produce specific anti-SilCR antibodies develop a significantly more severe infection. To our knowledge, this is a novel report demonstrating that specific antibodies against a bacterial component cause more severe infection by those bacteria.

Macrolide, lincosamide and tetracycline susceptibility and emm characterisation of invasive Streptococcus pyogenes isolates in Israel.

Group A beta-haemolytic streptococcus (GAS) causes a variety of infections, including life-threatening illnesses. Although the species is uniformly penicillin susceptible, resistance to other antibiotics is becoming more common. We studied the prevalence of resistance and associated factors in a nationwide, prospective, population-based study of invasive infections in Israel. Isolates were collected in collaboration with 24 hospitals in Israel during 1996-1999. Minimal inhibitory concentrations (MICs) of erythromycin (ERY), clindamycin (CLI) and tetracycline (TET) were determined as well as ERY and TET resistance phenotypes and genotypes. Five hundred isolates were examined: 136 (27.2%) were not susceptible to TET, 10 (2.0%) to ERY and 5 (1%) to CLI. ERY resistance was associated with emm types 12 and 83 (P<0.001 for both). MICs of TET had a bimodal distribution distinguishing sensitive and resistant populations. Non-susceptibility to TET was mainly due to the presence of tet(M) and was associated with T types 3, 3/13/B3624 and 9 and emm types 9, 33, 64, 73, 74, 76, 77 and 83. TET susceptibility was associated with T types 1, 2 and 11, emm types 1-4, 11, 12, 22, 26 and 75 and the presence of speA and speC. In Israel, resistance of invasive GAS isolates to ERY remains low and is associated with specific T and emm types, as is TET resistance. TET resistance is less frequent than previously reported in Israel and is associated with a lower prevalence of speA and speC.