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Simple model for the study of Pseudomonas aeruginosa infections in leukopenic mice.

A simple, reproducible model of fatal Pseudomonas aeruginosa sepsis in mice during immunosuppression was developed. Mice were rendered leukopenic (less than or equal to 800 leukocytes per mm3 of blood) for a period of 5 days by multiple injections of cyclophosphamide. Mice were challenged at the onset of leukopenia by instilling the bacteria onto a 0.5-mm incision made into the back. The mean lethal dose (LD50) for P. aeruginosa PA220 and M-2 was less than 20 bacteria. The mean time to death for these strains ranged from 46 to 59 h. Leukopenic mice were comparatively resistant when challenged with Klebsiella pneumoniae (LD50 = 1.5 x 10(6)) or Staphylococcus aureus (LD50 greater than 10(6)). Infection with P. aeruginosa was characterized by rapid bacterial multiplication in the skin at the site of infection, producing ecthyma gangrenosum. Bacteremia and colonization of the liver were pronounced 21 h postinfection. This model should prove to be a useful tool for studying the pathogenesis of P. aeruginosa infections under immunosuppressed conditions.

Animals↗

Humanized in vivo model for streptococcal impetigo.

An in vivo model for group A streptococcal (GAS) impetigo was developed, whereby human neonatal foreskin engrafted onto SCID mice was superficially damaged and bacteria were topically applied. Severe infection, indicated by a purulent exudate, could be induced with as few as 1,000 CFU of a virulent strain. Early findings (48 h) showed a loss of stratum corneum and adherence of short chains of gram-positive cocci to the external surface of granular keratinocytes. This was followed by an increasing infiltration of polymorphonuclear leukocytes (neutrophils) of mouse origin, until a thick layer of pus covered an intact epidermis, with massive clumps of cocci accumulated at the outer rim of the pus layer. By 7 days postinoculation, the epidermis was heavily eroded; in some instances, the dermis contained pockets (ulcers) filled with cocci, similar to that observed for ecthyma. Importantly, virulent GAS underwent reproduction, resulting in a net increase in CFU of 20- to 14,000-fold. The majority of emm pattern D strains had a higher gross pathology score than emm pattern A, B, or C (A-C) strains, consistent with epidemiological findings that pattern D strains have a strong tendency to cause impetigo, whereas pattern A-C strains are more likely to cause pharyngitis.

Animals↗

Disseminated invasive infection due to Metarrhizium anisopliae in an immunocompromised child.

The first reported human case of possible disseminated infection with the insect pathogen Metarrhizium anisopliae var. anisopliae, a fungus which has been used commercially for biocontrol of insects, is described. The patient, a 9-year-old boy, had a 5-year history of pre-B-cell acute lymphoblastic leukemia and had been on chemotherapy throughout this period. After 10 days of profound neutropenia, lesions consistent with ecthyma gangrenosum appeared on his arms and legs. M. anisopliae was grown from specimens from three separate sites, collected at different times over a period of 1 month: a skin biopsy, a swab from the base of a lesion, and the core of another skin lesion which spontaneously discharged. The initial skin biopsy also showed histological evidence of epidermal necrosis and dermal invasion with fungal hyphae. A computed-tomography (CT) scan of the chest demonstrated a lesion in the superior segment of the lower lobe of the left lung. A CT scan of the brain revealed a lesion in the left temporoparietal region of the brain, consistent with an abscess. Despite antifungal treatment including liposomal amphotericin and 5-flucytosine, the patient eventually died. The initial portal of entry is unknown, but hematogenous dissemination to the skin appears likely because of the multiple ecthymic lesions, and the appearances of the brain lesion on the CT scan are consistent with a hematogenous fungal abscess.

Child↗

Treatment of staphylococcal scalded skin syndrome.

Humans are a natural reservoir for Staphylococcal aureus. Colonization begins soon after birth and predisposes to infection. S. aureus is one of the most common causes of skin infection, giving rise to folliculitis, furunculosis, carbuncles, ecthyma, impetigo, cellulitis and abscesses. In addition, S. aureus may cause a number of toxin-mediated life-threatening diseases, including staphylococcal scalded skin syndrome (SSSS). Epidermolytic toxins released by certain S. aureus strains cause SSSS by cleaving the epidermal cell adhesion molecule, desmogelin-1, resulting in superficial skin erosion. Recent experiments have revealed similarities in the pathophysiology of SSSS and pemphigus foliaceus, an autoimmune disorder that is characterized by antibodies targeting the same epidermal attachment protein. SSSS typically affects neonates and infants but may also occur in predisposed adults. It is painful and distressing for the patient and parents, although most cases respond to antibiotic treatment. Mortality is low in infants but can be as high as 67% in adults, and is dependent on the extent of skin involvement and the comorbid state. Thus, the management of adults who develop SSSS remains a major therapeutic challenge. The antibody response against the toxins neutralizes their effect and prevents recurrence or limits the effects to the area of infection, which is known as bullous impetigo.

Animals↗

Atypical parapoxvirus infection in sheep.

This report describes the clinical and laboratory findings for 5 sheep from 3 different flocks with extensive proliferative skin lesions grossly resembling warts on the distal limbs. The lesions affected the front and rear extremities in all sheep, and 2 sheep also had lesions around the head. The sheep exhibited signs of pain when the lesions were touched, and most sheep were reluctant to move. Various empirical treatments, including systemic antibiotics, topical antibiotics, and antifungal ointments, were administered without clinical improvement. Diagnostic tests including skin biopsy and histopathology, examination of skin scrapings, bacteriology, mycology, electron microscopy of lesions, and immunohistochemical analysis demonstrated that the lesions were the result of parapoxvirus infection. All 5 animals were euthanized either because of the lack of resolution of clinical signs or a decision by the owner. These animals illustrate an atypical presentation of parapoxvirus infection in sheep (orf, contagious ecthyma, and scabby mouth). The infection appeared to be minimally contagious; however, the lesions did not spontaneously resolve. This appears to be the 1st report of such lesions in multiple sheep in North America, although similar lesions have been reported in Israel and the United Kingdom.

Animals↗

X-linked agammaglobulinemia presenting as pseudomonas aeruginosa septicemia.

Usually, presenting infections in children with agammaglobulinemia include pneumonia and otitis media caused by pyogenic bacteria. We report here two cases of Pseudomonas aeruginosa septicemia with ecthyma gangrenosum, in previously healthy boys, leading to the diagnosis of X-linked agammaglobulinemia.

Agammaglobulinemia↗

Aeromonas as a human pathogen.

Although the first Aeromonas strain was described by Zimmermann as early as in 1890, it took 60 years until Caselitz established human pathogenicity of strains then called "Vibrio jamaicensis". Since then, and especially in the last 10 years, there have been increasing numbers of reports on different infections caused by members of the genus Aeromonas. These include sepsis; meningitis; cellulitis; necrotizing fasciitis; ecthyma gangrenosum; pneumonia; peritonitis; conjunctivitis; corneal ulcer; endophthalmitis; osteomyelitis; suppurative arthritis; myositis; subphrenic abscess; liver abscess; cholecystitis and/or ascending cholangitis; urinary tract infection; endocarditis; ear, nose, and throat infections; balanitis; etc. The role of Aeromonas in gastrointestinal disease is very controversial. Increasing epidemiological data suggest that these organisms play a major role in enteric infections, but so far enteropathogenicity has not been demonstrable in experiments where volunteers were given high numbers of Aeromonas possessing different virulence factors. Virulence factors include hemolysin(s), enterotoxin(s), hemagglutinins, invasivity, and others; but these are not found more frequently in strains isolated from patients with diarrhea than from healthy controls. Whether there is a correlation between species and disease remains to be elucidated and requires more information about the taxonomy of this genus.

Aeromonas↗

Molecular weapons against agricultural vulnerability and the war on terror.

The multiple reports in this issue of the Journal from the Agenda for Action conference, coupled with the analysis by the National Academy of Sciences, the National Research Council, and the Auditor General (UK) on bioterror preparedness and homeland security, highlight the immediate need for rapid disease detection and advanced diagnostic capabilities to protect the public health, animal agriculture, and the numerous associated economies in the United States. In response to the potentially devastating consequences that could arise, there is an acute need for rapid detection of a variety of the lethal foreign animal diseases, such as foot-and-mouth disease virus (FMDV), highly pathogenic strains of avian influenza, classical swine fever, rinderpest, exotic Newcastle disease virus (END), and domestic, vesicular look-alike diseases that include bluetongue, epizootic hemorrhagic disease, vesicular stomatitis, bovine herpes IBR, contagious ecthyma, bovine herpes mammilitis virus, vesicular exanthema, malignant catarrhal fever, and papular stomatitis. Some striking advances are occurring in the creation of rapid technology, including microfluidics, robotics, miniaturization, and biostabilization that are quickly being applied to the development of rapid microbial detection assays. These are now providing important weapons to combat this agricultural vulnerability.

Animal Diseases↗

Experimental studies on mice challenged subcutaneously with Pseudomonas aeruginosa.

By use of the subcutaneous route, chronic Pseudomonas aeruginosa infections were established in normal mice undebilitated by burn wounds or leukopenic agents. Using a 21-day holding period, an LD50 value of 4.6 times 10(8) colony forming units was obtained. After subcutaneous infection, the dermis was completely necrosed with the lesions reaching deep into the subcutaneous tissue and musculature within 3-4 days. Ecthyma gangrenosum-like skin lesions at the site of infection appeared during this time period. By 7-15 days all mice exhibited a systemic infection. Both the livers and lungs showed a great deal of hemorrhage and frequently contained large necrotic foci, while the kidneys showed petechial hemorrhage and occasional renal abscesses. The susceptibility to infection was markedly increased by use of various antineoplastic agents and suprarenal hormones. However, the type of tissue damage or severity was not significantly altered as compared to infected mice which had not received any of the chemical agents.

Animals↗

Mucocutaneous and soft tissue infections caused by Xanthomonas maltophilia. A new spectrum.

OBJECTIVE: To describe the mucocutaneous and soft tissue infections caused by Xanthomonas maltophilia in patients with cancer. DESIGN: A retrospective 15-month clinical study. SETTING: Academic, referral-based cancer center. PATIENTS: Of 237 patients with X. maltophilia isolated from all sites during the 15-month study period, 114 patients were judged to have true X. maltophilia infections. Only patients with mucocutaneous and soft tissue infections were included in the study. RESULTS: 17 (15%) of the 114 patients with X. maltophilia infection had mucocutaneous and soft tissue infections: Six patients had metastatic cellulitis, 5 had primary cellulitis usually associated with catheter use, and 6 had infected mucocutaneous ulcers. The metastatic cellulitis consisted of previously undescribed multiple, hard, tender nodules with surrounding and distant cellulitis (5 patients) or ecthyma gangrenosum (1 patient). Four of these patients died of the infection. Metastatic cellulitis and mucocutaneous infections occurred in hospitalized, neutropenic patients who received broad-spectrum antibiotics (beta-lactams, quinolones), often with in vitro activity against the infecting organisms. Response usually correlated with recovery from myelosuppression and administration of trimethoprim-sulfamethoxazole with or without ticarcillin-clavulanate. Catheter removal contributed to response in the treatment of primary cellulitis. CONCLUSIONS: Mucocutaneous and soft tissue infections caused by X. maltophilia are not uncommon, and X. maltophilia can cause metastatic nodular skin lesions that mimic disseminated fungal infections. It also causes serious morbidity and high mortality in patients with metastatic skin nodules and can cause superinfections in patients receiving broad-spectrum beta-lactam or quinolone antibiotics to which the organisms are susceptible when the infections develop. Catheter removal contributes to a favorable outcome in patients with catheter-associated cellulitis without bacteremia. Xanthomonas maltophilia infection should be added to the differential diagnosis of mucocutaneous or soft tissue infection in patients with cancer. Trimethoprim-sulfamethoxazole with or without ticarcillin-clavulanate is the current treatment of choice for culture-proven infections, but early empiric therapy may improve outcome.

Adult↗

Hematologic, serum chemistry and serologic values of Dall's sheep (Ovis dalli dalli) in Alaska.

In June 1979, 73 Dall's sheep were captured near Tok, Alaska to determine selected hematologic and serum metabolite parameters and to determine the presence of antibodies to selected pathogens. Hematology and serum metabolite values were compared with values for domestic sheep and bighorn sheep (Ovis canadensis). Antibodies were detected against Brucella sp. (4%), Campylobacter feti (30%), contagious ecthyma virus (23%) and bovine parainfluenza type 3 virus (1%). Antibodies were not detected against Anaplasma sp., Leptospira sp., bovine virus diarrhea virus, bluetongue virus, infectious bovine rhinotracheitis virus, ovine progressive pneumonia, and Toxoplasma sp.

Alaska↗

Serologic survey for selected microbial pathogens in Alaskan wildlife.

Antibodies to Brucella spp. were detected in sera of seven of 67 (10%) caribou (Rangifer tarandus), one of 39 (3%) moose (Alces alces), and six of 122 (5%) grizzly bears (Ursus arctos). Antibodies to Leptospira spp. were found in sera of one of 61 (2%) caribou, one of 37 (3%) moose, six of 122 (5%) grizzly bears, and one of 28 (4%) black bears (Ursus americanus). Antibodies to contagious ecthyma virus were detected in sera of seven of 17 (41%) Dall sheep (Ovis dalli) and five of 53 (10%) caribou. Antibodies to epizootic hemorrhagic disease virus were found in sera of eight of 17 (47%) Dall sheep and two of 39 (6%) moose. Infectious bovine rhinotracheitis virus antibodies were detected in sera of six of 67 (9%) caribou. Bovine viral diarrhea virus antibodies were found in sera of two of 67 (3%) caribou. Parainfluenza 3 virus antibodies were detected in sera of 14 of 21 (67%) bison (Bison bison). Antibodies to Q fever rickettsia were found in sera of 12 of 15 (80%) Dall sheep. No evidence of prior exposure to bluetongue virus was found in Dall sheep, caribou, moose, or bison sera.

Alaska↗

Relationships among fecal lungworm loads, fecal glucocorticoid metabolites, and lamb recruitment in free-ranging Rocky Mountain bighorn sheep.

Most wild Rocky Mountain big-horn sheep (Ovis canadensis canadensis) in northern latitudes are infected with lungworms. Indirect effects of lungworms on bighorn sheep are unknown, but high pulmonary burdens might increase stress (i.e., elevated glucocorticoid levels), and chronic stress could in turn decrease fitness. We hypothesized that high lungworm burdens in Rocky Mountain bighorn ewes increase stress, thereby increasing lamb mortality. To test our hypothesis, one subherd of bighorn sheep in Custer State Park, South Dakota was provided a free-choice loose mineral mix containing the anthelmintic fenbendazole every six weeks from March 1999 to August 2000 to eliminate lungworms; another subherd served as the control. Daily, individually marked ewes were located telemetrically from the ground and uniquely marked animals were observed until they defecated. After the herd moved from the area, fecal samples were collected and stored at -23 C. A consistent number of samples per season per herd (x-=16.56+/-3.99 samples) were collected. Fecal larval lungworm levels (LPG) in the treatment subherd were lower than levels in the control subherd; however, there was no difference in fecal glucocorticoid metabolite (FGM) levels between the two subherds. Fecal glucocorticoid metabolite levels varied by season in both subherds, with levels in winter lower than during the other three seasons. Lamb:ewe ratios were not different between the control and treatment subherds at the end of summer 1999. In contrast, the treatment group had a lower lamb:ewe ratio at the end of summer 2000 despite having lower LPG. However, this result was attributed to lower ewe production, not lower lamb survival. The LPG levels were not correlated with FGM concentrations; instead, FGM levels might reflect normal seasonal patterns. Other factors, including contagious ecthyma, were more important for determining lamb mortality than LPG and FGM levels during our study. We suggest further experimental work over a longer duration to address these relationships.

Animals↗

Subcutaneous nodules caused by Pseudomonas aeruginosa without sepsis.

Pseudomonas aeruginosa infection can cause a wide array of skin manifestations. While some infections are mild, as are the cases with hot tub folliculitis and toe web or nail infection, others are a result of sepsis and can be fatal without prompt treatment. The classic skin finding of P. aeruginosa sepsis is Ecthyma gangrenosum, but other signs such as papules, petechiae, and hemorrhagic bullae can also be seen. Suppurative panniculitis can also be caused by P. aeruginosa sepsis and clinically manifests as solitary or multiple subcutaneous nodules. Reports in the literature describe these nodules in the setting of clinical sepsis or with positive blood cultures. We report a case of localized subcutaneous nodules on the leg caused by P. aeruginosa in a patient without sepsis or positive blood cultures. The source of the infection was thought to be from a traumatic inoculation. This raises the possibility that P. aeruginosa can cause subcutaneous nodules from a localized infection, perhaps via lymphangitic spread without the manifestations of sepsis.

Aged↗

Indolent cutaneous mucormycosis with pulmonary dissemination in an asthmatic patient: survival after local debridement and amphotericin B therapy.

We describe a 68-year-old asthmatic female patient with multiple pulmonary cavities. A preexisting ecthyma on the left lower leg became erythematous and swollen during exacerbation of her asthma which was under treatment with high-dose steroids. Nonseptate broad hyphae were found in her sputum, pus from the wound, and debrided skin tissue. Hematogenous spread of septic emboli from indolent cutaneous mucormycosis to both lungs was the suspected mechanism of dissemination. High-dose steroid therapy may have been the major contributory factor. The patient was successfully treated with local surgical debridement of the wound and intravenous amphotericin B.

Aged↗

Community-acquired Pseudomonas aeruginosa bacteremia and sepsis in previously healthy infants.

Pseudomonas aeruginosa bacteremia, or sepsis, often occurs in hospitals, affecting mainly children with underlying problems. However, it can also appear in communities, and affects infants and children without underlying diseases. We report eight cases of Pseudomonas aeruginosa bacteremia, or sepsis, in previously healthy infants over a three-year period. All patients were less than twelve months old and the majority presented with sepsis, diarrhea, ecthyma gangrenosum, and neutropenia. The infection route may have been the gastrointestinal tract. Concomitant gastrointestinal infections may have played a role in pathogenesis.

Bacteremia↗

[Para-infectious vasculitis].

Vasculitis is histologically characterized by inflammatory infiltrates of the vessels. In case of secondary vasculitis, the etiology is known. It may be an infection, a neoplasia, drugs or an autoimmune disease. In contrast, in primary vasculitis, no triggering event can be detected. In case of vasculitis associated to infection, the skin lesion may be the clue for the underlying infection. In case of endocarditis (Osler node, Janeway lesion) or sepsis due to Pseudomonas aeruginosa (ecthyma gangrenosum), the skin lesions are quite specific for the underlying disease. Other skin lesions are just an unspecific reaction to a microbial stimulus. Five clinical examples of vasculitis associated to infection, and an important non-infectious differential diagnosis are presented. The cases underline that a broad general work-up with multiple serological tests is neither cost-effective nor diagnostically rewardable. In contrast, if vasculitis is suspected to be caused by infection, the individual work-up should be based on the case-history, the epidemiology and the clinical presentation.

Adult↗

Xanthomonas maltophilia bacteremia: an analysis of 32 cases.

Thirty-two cases of Xanthomonas maltophilia bacteremia have been identified over the last two years at the Veterans General Hospital, Taipei. Among them, 27 cases (84%) were due to hospital-acquired infections, and 14 cases (44%) were polymicrobial bacteremia. One case was confirmed as prosthetic valve endocarditis and one case was complicated by recurrent attacks of ecthyma gangrenosum. Most cases had severe debilitating conditions. Twelve cases (38%) had a malignancy, 19 cases (59%) were resident in the Intensive Care Unit and 16 cases (50%) had undergone major surgery. The main predisposing factors included central venous catheterization, endotracheal intubation or tracheostomy, prior antibiotic therapy and prolonged hospitalization. Moxalactam, chloramphenicol and trimethoprim-sulfamethoxazole were the most effective agents in vitro against X. maltophilia. Twenty-two cases (69%) died during hospitalization; 13 cases (41%) were directly attributed to septicemia. Factors that adversely influenced mortality included inappropriate antimicrobial therapy and prior antibiotic treatment. Of particular interest is the fact that none of the patients who did not receive appropriate antimicrobial therapy survived. Early diagnosis and appropriate antibiotic therapy are critical for improving the prognosis of X. maltophilia infection.

Adult↗