Raymond A. Smego

Anaerobic spondylodiscitis: Case series and systematic review

Background: Bacterial spondylodiscitis is rarely caused by anaerobic organisms. We describe two patients with lumbar vertebral osteomyelitis and discitis caused by anaerobic bacteria, including an unusual occurrence after an endodontic procedure, and review the salient clinical features and outcomes of 31 previously reported cases. Methods: Case reports and review of the literature. Results: Median age at presentation was 65 years, with a male-to-female ratio of 2:1. The most common presenting symptoms were back pain, fever, and neurologic deficits. The lumbar spine was most frequently involved (43%); an equal number of cases involved contiguous extension or hematogenous spread. Causative anaerobes were recovered from disk space or vertebrae (13), blood (4), and/or soft tissue abscess and included Bacteroides species (12), Propionibacterium acnes (7), Peptococcus species (4), Peptostreptococcus species and Clostridium species (3 each), Corynebacterium diphtheroides and Fusobacterium species (2 each), and unspecified anaerobes (3). Conclusions: Apart from specific antibiotic selection, medical treatment and outcomes for anaerobic spondylodiscitis are similar to those for aerobic vertebral disk infection.

Cutaneous Manifestations of Anthrax in Rural Haiti

In industrialized countries, the zoonotic disease anthrax has been virtually eradicated because of effective public health measures including animal vaccination and quality control of animal products. In developing parts of the world, however, anthrax remains an occupational hazard of herdsmen and workers who have direct contact with infected animals or who process animal hides, hair, bone and bone products, and wool. For clinicians unfamiliar with this interesting infectious disease, the major dermatologic characteristics and clinical evolution of five cases of cutaneous anthrax are reviewed in this study in both descriptive and photographic forms, to define the clinical spectrum of cutaneous disease.

Four-year trends of inappropriate proton pump inhibitor use after hospital discharge.

Background Several hospital-based studies have determined that physicians often inappropriately prescribe acid-suppressive medications for stress ulcer prevention in hospitalized patients and continue these drugs after discharge. We sought to determine the frequency of inappropriate proton pump inhibitor (PPI) use continued at discharge within our geographic region. Methods We undertook a retrospective review of the medical records and pharmacy prescription database of a large regional insurance carrier from January 2005 through December 2008 (total hospital admissions 96,669). The primary inclusion criterion was hospital-initiated PPI therapy and continuation on hospital discharge without an appropriate indication. Patients receiving a PPI at the time of admission were excluded from the analysis. Results The number of patients per year discharged on a PPI decreased during the study period: 876 (2005), 763 (2006), 562 (2007), and 485 (2008). Of the patients discharged on a PPI, the number (%) of patients receiving PPIs inappropriately were 695 (79%; 2005); 627 (82%; 2006), 441 (78%; 2007), and 397 (82%; 2008). The annual number of PPI prescriptions and PPI doses dispensed decreased from 2015 to 1263 and from 60,608 to 38,742, respectively, during the study period. The estimated 4-year cost of inappropriate PPI use was

An Experimental Model for Naegleria fowleri-Induced Primary Amebic Meningoencephalitis in Rabbits

595,809, although cost savings from the absolute reduction in inappropriate PPI use over time was

In vitro Susceptibility Testing of Naegleria fowleri to Ketoconazole, BAYn7133, and Allopurinol Riboside

65,598. Conclusions We report a significant decrease of 39% in the number of inappropriate discharge prescriptions for PPIs during the study period; however, the percentage of inappropriate use of PPIs remains high. There is room for improvement in cost-effective use of PPIs.

Trimethoprim-Sulfamethoxazole Therapy for Nocardia Infections

A new model was developed in rabbits for primary amebic meningoencephalitis, a rare disease caused by the free-living ameba, Naegleria fowleri. Naegleria fowleri was cultured in a liquid axenic medium, and then injected intracisternally into New Zealand White rabbits. Inocula of 10(3) or 10(5) trophozoites consistently produced a sanguinopurulent meningitis; duration of survival of rabbits was 57 or 45 hr, respectively. Counts of cells in cerebrospinal fluid were proportional to the size of inoculum used; white blood cell counts ranged from 30 to 1,055 cells/mm3, and red blood cell counts from five to 8,640 cells/mm3. Necropsies revealed severe basilar meningoencephalitis with extensive hemorrhagic necrosis and polymorphonuclear cell infiltration. Trophozoites of N. fowleri were seen within the meningeal exudate and the brain parenchyma. Potential applications of this model include studies of the host response to amebae in the CSF, evaluation of the optimal route of administration of amphotericin B, and in vivo studies of other chemotherapeutic agents that show in vitro efficacy.

Combined Therapy with Amphotericin B and 5-Fluorocytosine for Candida Meningitis

Primary amebic meningoencephalitis is a rapidly fatal infection caused by the normally freeliving ameba, Naegleriafowleri. It usually affects previously healthy children and young adults, who contract the disease by swimming in warm, stagnant, fresh-water ponds and other bodies of water inhabited by N. fowleri. The amebae reach the meninges via intranasal passage. At present, no reliable therapy is available for this disease. Among approximately 135 cases reported worldwide, there have been only three well-documented instances of survival. The most recent success was a 9-yr-old girl who was treated with amphotericin B and miconazole (both given intravenously and intrathecally) plus oral rifampin (Seidel et al., 1982, New Engl. J. Med. 306: 346348). Because of the poor prognosis for patients with primary amebic meningoencephalitis, a wide array of chemotherapeutic agents have been tested for in vitro activity against N. fowleri. Drugs shown to have in vitro efficacy include amphotericin B (Duma and Finley, 1976, Antimicrob. Agents Chemother. 10: 370-376); miconazole, tetracycline, and rifampin (Duma and Finley, 1976, loc. cit.; Thong et al., 1977, Lancet 2: 876); and clotrimazole (Jamieson, 1975, J. Clin. Pathol. 28: 446-449). We have performed sensitivity testing on a strain of N. fowleri using three previously untried agents: ketoconazole (Janssen Pharmaceuticals, New Brunswick, New Jersey); BAYn7133, a new investigational imidazole (Miles Laboratories, West Haven, Connecticut); and allopurinol riboside, an investigational antiprotozoal drug (Burroughs-Wellcome, Research Triangle Park, North Carolina). Amphotericin B, which has known activity against N. fowleri, was used for comparison (E. R. Squibb and Son, Inc., Princeton, New Jersey). A strain of N. fowleri (W.M.) isolated from a fatal human case was generously supplied by Dr. Richard J. Duma, Division of Infectious Diseases, Medical College of Virginia, Richmond, Virginia. Organisms were cultured axenically in calf serum-casein-yeast extract liquid medium (Changs medium) (Chang, 1971, Curr. Top. Comp. Pathobiol. 1: 201-254) containing penicillin G, 100 U/ml, and streptomycin, 100 ,ug/ ml. To test drug susceptibility, an eight-chambered tissue culture chamber/slide system (LabTek?, Miles Laboratories, Naperville, Illinois) was used as described by Duma and Finley (1976, loc. cit.). Drugs were solubilized using sterile water, and then serially diluted in Changs liquid medium to yield concentrations of 0.018, 0.078, 0.31, 1.25, 5.0, 10, and 50 ,g/ml. With an automatic, nonelectric pipette, 0.1-ml suspensions containing 105 trophozoites/ml, counted using a hemocytometer, from 72 to 96 hr (37 C), liquid, axenic cultures of N. fowleri were added to individual chambers containing 0.4-ml aliquots of each drug concentration. To one chamber per slide, as a control, amebae were added to axenic media only. Chamber/slides were incubated at 37 C. Minimal inhibitory concentrations (MIC), defined as the lowest concentration of drug at which growth was 50% or less than that of control, were determined at 24 and 48 hr by visual examination using an inverted microscope; values for each drug were the same at 24 and 48 hr. These results are summarized in Table I. To determine if growth inhibition was an amebastatic or amebacidal phenomenon, chambers showing inhibition of growth of amebae were re-subcultured into Changs media, reincubated at 37 C for 48 hr, and observed for the presence of motile organisms. All subcultures failed to demonstrate viable amebae. Amphotericin B and ketoconazole both showed amebacidal effect on N. fowleri in vitro, whereas BAYn7133 or allopurinol riboside had no effect on the amebae at any of the concentrations tested. The MICs for amphotericin B were lower than those reported previously by Duma and Finley (1976, loc. cit.), but were comparable to those