Emergence of Extensively Drug-Resistant Salmonella Typhi Infections Among Travelers to or from Pakistan - United States, 2016-2018.

In February 2018, a typhoid fever outbreak caused by Salmonella enterica serotype Typhi (Typhi), resistant to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, fluoroquinolones, and third-generation cephalosporins, was reported in Pakistan. During November 2016-September 2017, 339 cases of this extensively drug-resistant (XDR) Typhi strain were reported in Pakistan, mostly in Karachi and Hyderabad; one travel-associated case was also reported from the United Kingdom (1). More cases have been detected in Karachi and Hyderabad as surveillance efforts have been strengthened, with recent reports increasing the number of cases to 5,372 (2). In the United States, in response to the reports from Pakistan, enhanced surveillance identified 29 patients with typhoid fever who had traveled to or from Pakistan during 2016-2018, including five with XDR Typhi. Travelers to areas with endemic disease, such as South Asia, should be vaccinated against typhoid fever before traveling and follow safe food and water practices. Clinicians should be aware that most typhoid fever infections in the United States are fluoroquinolone nonsusceptible and that the XDR Typhi outbreak strain associated with travel to Pakistan is only susceptible to azithromycin and carbapenems.

H1N1 encephalitis with malignant edema and review of neurologic complications from influenza.

BACKGROUND: Influenza virus infection of the respiratory tract is associated with a range of neurologic complications. The emergence of 2009 pandemic influenza A (H1N1) virus has been linked to neurological complications, including encephalopathy and encephalitis. METHODS: Case report and literature review. RESULTS: We reviewed case management of a 20-year old Hispanic male who developed febrile upper respiratory tract signs and symptoms followed by a confusional state. He had rapid neurologic decline and his clinical course was complicated by refractory seizures and malignant brain edema. He was managed with oseltamavir and peramavir, corticosteroids, intravenous gamma globulin treatment, anticonvulsants, intracranial pressure management with external ventricular drain placement, hyperosmolar therapy, sedation, and mechanical ventilation. Reverse transcriptase polymerase chain reaction analysis of nasal secretions confirmed 2009 H1N1 virus infection; cerebrospinal fluid (CSF) was negative for 2009 H1N1 viral RNA. Follow-up imaging demonstrated improvement in brain edema but restricted diffusion in the basal ganglia. We provide a review of the clinical spectrum of neurologic complications of seasonal influenza and 2009 H1N1, and current approaches towards managing these complications. CONCLUSIONS: 2009 H1N1-associated acute encephalitis and encephalopathy appear to be variable in severity, including a subset of patients with a malignant clinical course complicated by high morbidity and mortality. Since the H1N1 influenza virus has not been detected in the CSF or brain tissue in patients with this diagnosis, the emerging view is that the host immune response plays a key role in pathogenesis.

Neonatal invasive group A streptococcal disease: case report and review of the literature.

We present a fatal case of neonatal invasive group A streptococcal disease and review of the literature. Twenty-four cases were early onset disease and were associated with concurrent maternal infection, respiratory distress, pneumonia, toxic shock-like syndrome and serotype M1. Fifteen cases were late onset disease associated with soft tissue infections and meningitis. Maternal carriage was identified as an important factor in neonatal group A streptococcal disease.

Perioperative management of neurosurgical patients with methicillin-resistant Staphylococcus aureus.

OBJECT: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has posed a challenge in the treatment of neurosurgical patients. The authors investigated the impact of MRSA colonization and infection in the neurosurgical population at a community-based, tertiary care referral center. METHODS: Hospitalized patients under the care of the Kaiser Permanente inpatient neurosurgery service were prospectively entered into a database. In Phase I of the study, 492 consecutive patients were followed. Per hospital policy, the 260 patients from this group who were admitted to the intensive care unit (ICU) underwent screening for MRSA based on nasal swab cultures and a review of their medical history for prior MRSA infections. These patients were designated as either MRSA positive (17 patients, 6.5% of screened patients) or MRSA negative (243 patients). The 232 patients admitted to non-ICU nursing units did not undergo MRSA screening and were designated as unscreened. In Phase II of the study, the authors reviewed 1005 neurosurgical admissions and completed a detailed chart review in 62 MRSA-positive patients (6.2%). Eleven patients received nonoperative treatment. Five patients presented with community-acquired neurosurgical infections, and the causative organism was MRSA in 3 cases. Forty-six patients underwent 55 procedures, and the authors reviewed their perioperative management. RESULTS: In Phase I of the study, the authors found that for the MRSA-positive, MRSA-negative, and unscreened groups, the rates of postoperative neurosurgical wound infections caused by all pathogens were 23.5, 4.1, and 1.3%, respectively. For MRSA wound infections, the rates were 23.5, 0.8, and 0%, respectively. In Phase II, patients with MRSA were noted to have the following clinical features: male sex in 63%, a malignancy in 39.1%, diabetes in 34.8%, prior MRSA infection in 21.7%, immunosuppressed state in 17.4%, and a traumatic injury in 15.2%. The rate of postoperative neurosurgical wound infection in patients who received MRSA-specific prophylactic antibiotic therapy (usually vancomycin) was 7.4% (27 procedures) compared with 32.1% (28 procedures) in patients who received the standard treatment (usually cefazolin) (p = 0.04). Wound care for ICU patients was standardized for postoperative Days 0-7 with chlorhexidine cleaning at bandage changes at 3-day intervals. Wound cultures from neurosurgical site infections in patients with prior MRSA colonization or infection grew MRSA in 7 of 11 patients. CONCLUSIONS: Neurosurgical patients identified with MRSA colonization or a prior history of MRSA infections benefit from specific perioperative care, including prophylactic antibiotics active against MRSA (such as vancomycin) and postoperative wound care with coverings and chlorhexidine antisepsis to reduce MRSA wound colonization.

The role of toll-like receptors in herpes simplex infection in neonates.

Toll-like receptors (TLRs)--and their associated signal-transducing proteins--on the surface of cells have been demonstrated to account for most, if not all, of the events associated with bacterial sepsis. Using human cells expressing different TLRs, we demonstrated that the interaction between TLR2 and herpes simplex virus (HSV)-1-2 leads to the production of cytokines. Using peripheral-blood mononuclear cells, we tested the ability of cells from people of different age groups to make cytokines in response to HSV. An examination of the host responses of neonates to HSV indicates that, rather than producing less interleukin-6 and interleukin-8 in response to HSV than adults do, neonates produce more of these cytokines than adults do. This may explain the sepsis syndrome that is seen with HSV (and other virus infections) in neonates.

Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2.

Human cytomegalovirus (CMV) is a ubiquitous opportunistic pathogen that causes significant morbidity and mortality in immunocompromised people. An understanding of how CMV induces and circumvents host immunity is of critical importance in efforts to design effective therapeutics. It was recently discovered that mere cell contact by CMV particles leads to profound modulation of cellular gene expression, including induction of inflammatory cytokines and interferon-stimulated genes characteristic of innate immune detection. These findings suggest that a membrane receptor recognizes a CMV envelope protein(s), leading to innate immune activation. Here, we show that the pattern recognition receptors Toll-like receptor 2 (TLR2) and CD14 recognize CMV virions and trigger inflammatory cytokine production. Induction of inflammatory cytokines is mediated via TLR2-dependent activation of NF-kappa B. Since many of the pathological processes associated with CMV disease are facilitated or directly mediated by inflammatory cytokines, identification of the host membrane detection machinery may ultimately lead to improved therapeutics.