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.

Lack of Pharmacokinetic Basis of Weight-Based Dosing and Intra-Operative Re-Dosing with Cefazolin Surgical Prophylaxis in Obese Patients: Implications for Antibiotic Stewardship.

Traditionally, there have been uniform antibiotic dosing guidelines for prophylaxis for clean-clean-contaminated surgery in both non-obese and obese adults. All other factors predisposing to surgical site infections (SSIs) being equal, over time, the preferred drug is cefazolin. The usual dose, given immediately pre-procedure, has been 1 g intravenously (IV) in non-penicillin-allergic patients, which has been highly effective, Recently, it has become common practice to use high-dose cefazolin; i.e., 3 g IV, in obese patients. This article reviews the literature on high-dose cefazolin prophylactic regimens in the obese from a pharmacokinetic (PK) point of view. There are no comparative studies to support this approach, which is based largely on the theory "more must be better." Weight-based dosing of cefazolin in the obese is flawed, because it does not take into account PK factors, which are critical in the obese. Cefazolin is a water-soluble (hydrophilic) antibiotic that does not penetrate adipose tissue regardless of IV dose. Importantly, adipose tissue is not a valid target tissue in clean-clean-contaminated SSI prophylaxis, as it does not become infected. Higher doses result in proportionately higher serum/non-adipose tissue concentrations, but adipose tissue concentrations are unaffected. Cefazolin displays time-dependent killing kinetics so that as long as serum/tissue concentrations are above the minimum inhibitory concentration (MIC) of SSI pathogens, there is no enhanced killing with higher concentrations relative to concentration-dependent antibiotics. Taking into account PK principles, a cefazolin 1 g IV bolus results in peak serum concentrations of ∼185 mcg/mL, provides at least six hours of intra-operative protection, aside from any post-antibiotic effects, and eliminates any rationale for intra-operative re-dosing for procedures lasting six hours or less. Some have argued that a cefazolin 3 g IV dose in the obese does not matter, as more must necessarily be better. However, from an antibiotic stewardship program (ASP) perspective, unneeded antibiotics are unnecessary. Moreover, the costs of cefazolin 1 g (IV push) at $0.75 versus 2 g (IV piggyback) at $ 6.83 can be significant in large centers using cefazolin prophylaxis for cardiothoracic, orthopedic, obstetric/gynecology, and bariatric surgery. Excessive antibiotics also expose the patient to potential adverse effects; i.e., Clostridium difficile. There is no dose-dependent or duration of exposure effect on resistance with one or two pre-operative or intra-operative doses. Well-done PK-based studies in obese patients clearly demonstrate the lack of benefit of using a 3-g dose or intra-operative re-dosing and show no incremental increase in adipose tissue concentrations with high doses. From an ASP point of view, antibiotic dosing recommendations should be reviewed and revised on the basis of PK principles that indicate that weight-based dosing has no basis for pre-operative prophylaxis in obese patients.

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.

How safe is doxycycline for young children or for pregnant or breastfeeding women?

Tetracycline antimicrobials entered into clinical usage in the late 1940s. Permanent dental staining from tetracyclines was first appreciated in 1956, eventually leading to avoidance of this class of antibiotics whenever possible in young children and pregnant or breastfeeding women. Doxycycline, introduced in 1967, binds calcium less avidly than prior tetracyclines and is regarded by some authorities as safe to prescribe for pregnant women and young children. Review of the available data, however, suggests that this interpretation may be incorrect or at least premature. In conclusion, until more definitive data are developed, doxycycline should continue to be only selectively prescribed for young children and pregnant or breastfeeding women for whom alternative, safer antibiotics are not available, and courses of treatment should be of as short a duration as possible.

A rare case of influenza A in a hospitalized adult presenting with encephalitis and a seizure.

Influenza A in hospitalized adults uncommonly may present with neurologic manifestations, e.g., encephalitis. Encephalitis is the most common influenza related neurologic complication in adults, However, seizures in hospitalized adults due to influenza are extremely rare. This is a case of a 58 year old female hospitalized for influenza A. On admission, she was confused and obtunded. Her EEG showed diffuse global slowing indicative of encephalitis. On hospital day (HD) #2, she had a seizure. She had no history of a seizure disorder, and was not febrile at the time of the seizure. While seizures are not uncommon in children (febrile seizures) with influenza B, but in adults with influenza A, only a few cases of seizures have been reported. This case was most interesting in having both encephalitis and seizure complicating influenza A. If present, neuropsychiatric manifestations may be due to ostelamivir, but encephalitis and seizures are not among the neurologic adverse effects of ostelamivir. In adults hospitalized with influenza A, clinicians should be alert to the possibility of neurologic complications.

Intracranial complications of acute bacterial endocarditis.

BACKGROUND: Infectious endocarditis (IE) clinically manifests as either subacute bacterial endocarditis (SBE) or acute bacterial endocarditis (ABE). Neurologic manifestations are markedly different for these two entities. ABE is caused by invasive, highly virulent pathogens (e.g., Staphylococcus aureus), whereas SBE is attributed to relatively avirulent, non-invasive organisms (e.g., viridans streptococci). METHODS: Here, we reviewed the clinical and radiographic presentations of a patient with cranial complications attributed to ABE. Such patients typically develop central nervous system (CNS) septic emboli resulting in stroke (with/without intracranial hemorrhage (ICH)) and/or mycotic aneurysms resulting in ICH bleeds. RESULTS: With ABE, cerebrospinal fluid (CSF) seeding may result in acute bacterial meningitis (ABM), documented by positive Gram stain and/or culture for S. aureus, decreased glucose, highly elevated lactose acid levels, or ICH. Alternatively, in SBE, the CSF profile reflects an aseptic (viral) meningitis (i.e., Gram stain and culture negative, a normal glucose, and lymphocytic pleocytosis), while septic microemboli to the vasa vasorum contribute to an inflammatory reaction in the adventitia/muscle layer that weakens the vessel wall and results in mycotic aneurysms that may leak but often do not rupture causing ICH. CONCLUSION: Here, we reviewed the literature for intracranial pathology accompanying ABE versus SBE. ABE typically results in acute ischemia, septic emboli, stroke/hemorrhagic infarcts, or ICH. SBE more classically produces septic microemboli and mycotic aneurysms that may leak, but rarely producing ICH. We also presented a patient with ABE attributed to S. aureus whose septic emboli/stroke was accompanied by a mycotic aneurysm; the ruptured resulting in a large right occipital ICH.

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.

Enhanced Efficacy of High Dose Oral Vancomycin Therapy in Clostridium difficile Diarrhea for Hospitalized Adults Not Responsive to Conventional Oral Vancomycin Therapy: Antibiotic Stewardship Implications.

Current therapy of Clostridium difficile diarrhea (CDD) is problematic. Optimal treatment for CDD remains oral vancomycin, but there is little data on oral vancomycin dosing regimens. The objective of this C. difficile diarrhea study was to compare the efficacy of "high dose" vancomycin, 500 mg (PO) q6h, as sole treatment and in those who after 72 h failed to respond to conventional doses of oral vancomycin, 125-250 mg (PO) q6h. Hospitalized adults with CDD were evaluated by various oral vancomycin regimens, i.e., a conventional dose group (125-250 mg (PO) q6h), a "high dose escalation" dose group (250 mg → 500 mg (PO) q6h), and a "high dose" group (500 mg (PO) q6h). Oral vancomycin treatment groups were compared by time to improvement, i.e., decrease in >50% of watery stools/day and duration of therapy. The high dose escalation and high dose oral vancomycin groups showed the most rapid resolution of diarrhea. There was marked decrease in stools/day after "high dose" vancomycin escalation from conventional dosing, i.e., 250 mg (PO) q6h → 500 mg (PO) q6h. This study demonstrated that "high dose" escalation or initial high dose oral vancomycin, i.e., 500 mg (PO) q6h was the most efficacious regimen for CDD.

Once Daily High Dose Tigecycline Is Optimal: Tigecycline PK/PD Parameters Predict Clinical Effectiveness.

OBJECTIVE: The clinical effectiveness of tigecycline depends on appropriate use, and PK/PD (pharmacokinetic/pharmacodynamic) parameters related to dose and dosing interval. METHODS: In our 600-bed university-affiliated teaching hospital, we conducted a tigecycline efficacy review over a three-month period in 34 evaluable patients. Parameters assessed included clinical response, cure or treatment failure, once daily as q12h dosing, maintenance dosing, high dose vs. standard loading regimens, adverse effects, and the effect of infectious disease consultation on outcomes. RESULTS: We found once daily high dose tigecycline (HDT) was highly effective in treating serious systemic infections due to MDR Gram-positive/negative pathogens as well as C. difficile colitis. Adverse effects were infrequent and limited to mild nausea/vomiting. Once daily HDT was highly effective, and the few treatment failures were related to suboptimal/split dosing regimens. CONCLUSION: Once daily HDT was highly effective when used to treat susceptible pathogens and when optimally dosed, i.e., 200-400 mg (IV) loading dose ×1, followed by a once daily maintenance dose of 100-200 mg (IV) q24h.

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).

Lyme carditis with isolated left bundle branch block and myocarditis successfully treated with oral doxycycline.

Lyme disease may present with a variety of cardiac manifestations ranging from first degree to third degree heart block. Cardiac involvement with Lyme disease may be asymptomatic, or symptomatic. Atrioventrical conduction abnormalities are the most common manifestation of Lyme carditis. Less common, are alternating right bundle branch block (RBBB) and left bundle branch block (LBBB). We present an interesting case of a young male whose main manifestation of Lyme carditis was isolated LBBB. He also had mild Lyme myocarditis. The patient was successfully treated with oral doxycycline, and his isolated LBBB and myocarditis rapidly resolved.

Recurrent FUO due to intermittent Enterobacter cloacae bacteremias from an infected pacemaker lead diagnosed by gallium scan.

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. Recurrent FUOs are due to the same causes of classical FUOs. Recurrent FUOs may have continuous or intermittent fevers and are particularly difficult to diagnose. With intermittent fever, recurrent FUO diagnostic tests are best obtained during fever episodes. With recurrent FUOs, the periodicity of febrile episodes is unpredictable. We present a case of a 70-year-old male who presented with recurrent FUO. Multiple extensive FUO workups failed to determine the source of his fever. During his last two episodes of fever/chills, blood cultures were positive for Enterobacter cloacae. Episodic E. cloacae bacteremias suggested a device-related infection, and the patient had a penile implant and permanent pacemaker (PPM). Following febrile episodes, he was treated with multiple courses of appropriate antibiotics, but subsequently fever/chills recurred. Since a device-associated infection was suspected, indium and PET scans were done, but were negative. The source of his intermittent E. cloacae bacteremias was finally demonstrated by gallium scan showing enhanced uptake on a cardiac lead, but not the penile implant or PPM. Gallium scanning remains useful in workup of FUOs, particularly when false-negative indium or PET scans are suspected. The involved pacemaker lead was explanted, grew E. cloacae and the patient has since remained fever free.