Pharmacokinetic considerations in selecting optimal antibiotic therapy for Mycoplasma pneumoniae encephalitis.

Effective antimicrobial therapy depends on several factors including degree of activity against the pathogen, antibiotic resistance, and when relevant, optimal tissue penetration factors. Central nervous system (CNS) infections illustrate these points well. The pharmacokinetic (PK) parameters important in antibiotic blood cerebrospinal fluid barrier (BCB) penetration that is important in meningitis are different and do not predict blood brain barrier (BBB) penetration. Recently, we had a case of Mycoplasma pneumoniae encephalitis (MPE) which prompted a review of the antibiotic PK determinants of BBB penetration which differ markedly from those of BCB penetration important in encephalitis. Using MPE as an illustrative example, this article reviews host and drug factors of therapeutic importance in optimally treating MPE.

Fever of unknown origin (FUO): CMV infectious mononucleosis or lymphoma?

Fever of unknown origin (FUO) refers to fevers of > 101 °F that persist for > 3 weeks and remain undiagnosed after a focused inpatient or outpatient workup. FUO may be due to infectious, malignant/neoplastic, rheumatic/inflammatory, or miscellaneous disorders. The FUO category determines the focus of the diagnostic workup. In the case presented of an FUO in a young woman, there were clinical findings of both CMV infectious mononucleosis or a lymphoma, e.g., highly elevated ESR, elevated ferritin levels, and elevated ACE level, ß-2 microglobulins. The indium scan showed intense splenic uptake. Lymph node biopsy, PET scan, and flow cytometry were negative for lymphoma. CMV infectious mononucleosis was the diagnosis, and she made a slow recovery.

Study of the radiologic features of Legionnaires' disease with mediastinal adenopathy: Legionella or lymphoma?

An index case of Legionnaires's disease with mediastinal adenopathy prompted us to review our recent experience with Legionnaires' disease to determine the incidence of mediastinal adenopathy of this finding in Legionnaires' disease. We reviewed the radiographic findings of 90 hospitalized adults with Legionnaires' disease from 2015 to 2017. Excluded were 11 patients with mediastinal adenopathy due to non-Legionnaires' disease causes, e.g., lymphoma. Thirty-seven of the remaining patients had both chest films and chest computed tomography (CT) scans. Of the 37 Legionnaires' disease cases, 13/37 (35%) had mediastinal adenopathy and 8/27 (24%) also had unilateral hilar adenopathy. These chest CT findings were not seen on chest films. Chest CT scans are needed to detect mediastinal adenopathy in Legionnaires' disease. Mediastinal adenopathy may be due to Legionnaires' disease or a malignancy. Some findings in Legionnaires' disease are also present in mediastinal adenopathy due to lymphomas, e.g., highly elevated erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), and ferritin. Hospitalized adults with Legionnaires' disease and mediastinal adenopathy should have serial chest CT scans to monitor resolution of the mediastinal adenopathy. In hospitalized adults with otherwise unexplained persistent mediastinal adenopathy, they should be considered as being due to another etiology, e.g., lymphoma, until proven otherwise.

Lessons learned from splenic infarcts with fever of unknown origin (FUO): culture-negative endocarditis (CNE) or malignancy?

Culture negative endocarditis (CNE) is a common concern in patients with fever, heart murmur, cardiac vegetation, and negative blood cultures. The diagnosis of CNE is not based only on negative blood cultures and a cardiac vegetation. The clinical definition of CNE is based on negative blood cultures plus the findings of culture positive infective endocarditis (IE), e.g., fever, cardiac vegetation, splenomegaly, peripheral manifestations. Because embolic splenic infarcts may occur with culture positive IE, some may assume that splenic infarcts are a sign of CNE. Previously, CNE was due to fastidious and non-culturable organisms. With current diagnostic methods, fastidious organisms grow in 2-3 days. Therefore, fastidious IE are a subset of culture positive IE, but do not represent true CNE. We describe a case of an elderly female who presented with a fever of unknown origin (FUO) and multiple splenic infarcts thought by some to represent CNE. An extensive workup for CNE pathogens was negative. The final cause of her splenic infarcts was a diffuse large B-cell lymphoma (DLBCL). Review of the literature, as well as this case, confirms that splenic infarcts are not a feature of CNE. In patients with fever, splenic infarcts, and negative blood cultures, physicians should search for an alternate explanation rather than CNE, e.g., malignancy and hypercoaguable state (lupus anticoagulant).

Legionnaires' disease.

Since first identified in early 1977, bacteria of the genus Legionella are recognised as a common cause of community-acquired pneumonia and a rare cause of hospital-acquired pneumonia. Legionella bacteria multisystem manifestations mainly affect susceptible patients as a result of age, underlying debilitating conditions, or immunosuppression. Water is the major natural reservoir for Legionella, and the pathogen is found in many different natural and artificial aquatic environments such as cooling towers or water systems in buildings, including hospitals. The term given to the severe pneumonia and systemic infection caused by Legionella bacteria is Legionnaires' disease. Over time, the prevalence of legionellosis or Legionnaires' disease has risen, which might indicate a greater awareness and reporting of the disease. Advances in microbiology have led to a better understanding of the ecological niches and pathogenesis of the condition. Legionnaires' disease is not always suspected because of its non-specific symptoms, and the diagnostic tests routinely available do not offer the desired sensitivity. However, effective antibiotics are available. Disease notification systems provide the basis for initiating investigations and limiting the scale and recurrence of outbreaks. This report reviews our current understanding of this disease.

Fever of unknown origin (FUO) in a renal transplant recipient due to drug fever from sirolimus.

INTRODUCTION: A variety of medications may cause drug fever. Drug fevers may persist for days to weeks until diagnosis is considered. The diagnosis of drug fever is confirmed when there is resolution of fever within 3 days after the medication is discontinued. Only rarely do undiagnosed drug fevers persist for over 3 weeks to meet fever of unknown origin (FUO) criteria. FUOs due to drug fever are uncommon, and drug fevers due to immunosuppressive drugs are very rare. CASE REPORT: This is a case of a 58-year-old female renal transplant recipient who presented with FUO that remained undiagnosed for over 8 weeks. DISCUSSION: We believe this is the first reported case of an FUO due to drug fever from sirolimus in a renal transplant recipient.

A Case of Pneumonia Caused by Pneumocystis Jirovecii and Cryptococcus Neoformans in a Patient with HTLV-1 Associated Adult T- Cell Leukemia/Lymphoma: Occam's Razor Blunted.

Adult T-cell leukemia/lymphoma (ATLL) is usually preceded by infection with human T-cell lymphotropic virus I (HTLV-I). Patients with ATLL frequently get opportunistic infections of the lungs, intestines, and central nervous system. Pneumocystis pneumonia is commonly known as an AIDS defining illness. Grocott's methenamine silver stain of bronchoalveolar lavage (BAL) samples obtained via bronchoscopy remain the gold standard for diagnosis. Pulmonary cryptococcosis is seen in patients with T-cell deficiencies and a diagnosis is made by culture of sputum, BAL, or occasionally of pleural fluid. We present the second case of coinfection with these two organisms in a patient with ATLL who was successfully treated with trimethoprim-sulfamethoxazole, corticosteroids, and fluconazole. We illustrate the need for high clinical vigilance for seeking out an additional diagnosis, especially in immunocompromised patients if they are not improving despite receiving appropriate treatment.

During influenza season: all influenza-like illnesses are not due to influenza: dengue mimicking influenza.

BACKGROUND: During influenza season, many patients present to the emergency department (ED) for evaluation with influenza-like illnesses (ILIs). ILIs are commonly due to influenza A or B, but other infections may mimic influenza in their clinical presentation. With the high volume of ILIs presenting to the ED during influenza season, the ED physician should be alert to other infections masquerading as influenza. CASE REPORT: We report an interesting case of a 31-year-old female who presented with an ILI during influenza season. She had recently been in contact with multiple people with influenza. Her nonspecific laboratory tests done in the ED were consistent with influenza, except for a highly elevated serum ferritin level. The serum ferritin level was the key finding that led to the correct diagnosis of dengue fever, which she acquired during a recent trip to Haiti. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: During influenza season, facing high patient volumes of ILIs in the ED, the ED physician needs to be aware of clinical features in ILIs that may suggest a mimic of influenza.

Erdheim-Chester disease: a rare cause of recurrent fever of unknown origin mimicking lymphoma.

We report the case of a patient with recurrent fever of unknown origin (FUO) with prominent back pain, hepatosplenomegaly, and abdominal/pelvic adenopathy suggesting lymphoma. A bone biopsy showed histiocytic infiltration. Studies for lymphoma were negative, but immunohistochemical stains were diagnostic of Erdheim-Chester disease (ECD). ECD should be included as a rare cause of recurrent FUO with bone involvement.

Are ESR/CRP ratios helpful in differentiating West Nile encephalitis from non-West Nile virus meningitis/encephalitis?

West Nile encephalitis (WNE) may mimic other acute central nervous system infections in endemic areas. The laboratory diagnosis of WNE often takes several days. We review our recent experience of WNE to determine if the erythrocyte sedimentation rate/C-reaction protein ratio would be helpful in the early/presumptive diagnosis of WNE in hospitalized adults.

Biological terrorism and the allergist's office practice.

During the anthrax outbreak and threat in Trenton (2001), our allergy practice experienced increased visits from approximately 50 of our regular patients with symptoms they believed resulted from anthrax exposure. In all cases, their symptoms were caused by a combination of an exacerbation of their underlying allergic disease and anxiety because of possible exposure to anthrax. Our objective is to present an orderly approach to the allergist's outpatients presenting with possible exposure to a bioterrorist's agent. The 10 precepts of approach to the management of a biological casualty (index of suspicion, protect yourself, patient assessment, decontaminate, diagnose, treat, infection control, alert authorities, assist in investigation, and maintain proficiency) and the epidemiological characteristics of a biological attack are discussed. In table form, we compared the signs and symptoms of the most common outpatient consultations to an allergist's office practice (chronic rhinitis, asthma, food allergy, venom allergy, atopic dermatitis, drug allergy, chronic urticaria, acute urticaria, immunodeficiency, and anaphylaxis) with those of likely bioterrorism threats. Descriptions of smallpox, plague, tularemia, anthrax, viral hemorrhagic fevers, Q fever, brucellosis, Venezuelan equine encephalitis, glanders, and melioidosis are presented. Patients may readily mistake their allergic symptoms with those of infection with a bioterrorist's agent. At the same time, the allergist may be faced with one of his own chronic patients presenting with symptoms resembling their allergic disease but actually caused by one of the aforementioned pathogens.

Varicella-zoster virus meningoencephalitis in an immunocompetent patient without a rash.

Varicella-zoster virus (VZV) is an unusual cause of meningoencephalitis in the immunocompetent patient. Most cases of VZV-associated aseptic meningitis or encephalitis are associated with the skin rash of primary varicella, localized herpes zoster, or disseminated zoster. We report a case of VZV meningoencephalitis without a rash occurring in a normal host.

The effect of probiotics on the incidence of Clostridioides difficile: Retrospective cohort analysis.

BACKGROUND: Conflicting evidence exists regarding probiotics and the incidence of Clostridioides difficile infection (CDI). This study evaluates whether probiotics are efficacious for CDI prophylaxis in patients receiving antibiotics. METHODS: A retrospective cohort analysis of patients admitted to NYU Winthrop Hospital who received at least 1 dose of antibiotics considered high risk of inducing CDI. Patients were grouped according to probiotic use; association between probiotic use and incident CDI was examined. A model for incident CDI adjusting for known CDI risk factors was estimated. RESULTS: Of 3,267 patients, 4.6% had CDI within 12 weeks of antibiotics initiation. A total of 5.1% received probiotics within 24 hours of initiation, and 6.6% initiated probiotics during the 12-week follow-up. Of those taking probiotics within 24 hours of antibiotics, 9.6% had CDI, and of those not taking probiotics 4.2% had CDI (relative risk, 2.3; 95% confidence interval, 1.4, 3.7). In time-dependent Cox models accounting for probiotic initiation and adjusting for potential confounders, a positive association between probiotics and CDI remained significant (hazard ratio, 2.7; P < .001). DISCUSSION: Patients who received antibiotics with concurrent probiotics were more likely to have an incident of CDI compared with those who did not receive probiotics. Additional risk factors were histamine 2 receptor antagonists, proton pump inhibitors, and administration of multiple antibiotics simultaneously. CONCLUSIONS: The present study, because of its large population and inclusion of multiple variables playing a role in CDI, serves as a valuable resource when considering efficacy of probiotics as CDI prophylaxis.

Legionnaire's disease presenting with encephalitis, myoclonus, and seizures: Successful treatment with doxycycline.

Legionnaire's disease (LD) is a non-zoonotic atypical community acquired pneumonia (CAP) with several characteristic extra-pulmonary findings. Pending diagnostic test results, selected characteristic findings when considered together are the basis of clinical syndromic diagnosis and the basis of empiric antimicrobial therapy. Of the extra-pulmonary manifestation of LD, neurologic findings are among the most common, e.g., headache, mental confusion. In LD, encephalitis is rare as are myoclonus and seizures. This is a most interesting case of LD that presented with encephalitis, myoclonus and seizures. Pulmonary infiltrates developed early after admission. LD was suspected on the basis of otherwise unexplained characteristic findings, e.g., hypophosphatemia, elevated serum transaminases, microscopic hematuria, elevated ferritin, and empiric doxycycline therapy was started. The diagnosis of LD was further supported by prominent and persistent myoclonus and seizures, rare but characteristic neurologic findings in LD. On week 12 of hospitalization, he finally seroconverted with negative urinary antigen tests indicating his LD was due to a non-L. pneumophilia (serotype 01) strain. On doxycycline, he made a slow but complete recovery. We believe this is the first reported case of LD presenting with encephalitis, myoclonus, and seizures successfully treated with doxycycline.

HIV adult with fever and shortness of breath: Influenza B misdiagnosed as Pneumocystis (carinii) jiroveci pneumonia (PCP).

Clinical correlation is essential in assessing the relevance of the patient's history and physical findings in making a clinical presumptive diagnosis. False diagnostic associations may result in misdiagnosis. We present a case of an elderly female with HIV on HAART who presented with shortness of breath assumed to have Pneumocystis (carinii) jiroveci pneumonia (PCP) even though she had a clinical diagnosis of influenza B. She was thought to have PCP only because she had HIV. Tests for PCP were negative including BAL staining. Influenza B present in her respiratory secretions by PCR and was also cultured from BAL fluid. Diagnostic associations are helpful in suggesting diagnostic possibilities but must be supported by clinical correlation of characteristic clinical features.