Capnocytophaga canimorsus septicemia: Fifth report of a cat-associated infection and five other cases

Capnocytophaga canimorsus is a fastidious, slow-growing, gram-negative, rod-shaped bacterium that belongs to the normal oral flora of dogs and cats. Human septicemic infections are associated with a high mortality; most cases occur in immunocompromised patients with a history of dog bite. The fifth case of cat-associated septicemia caused byCapnocytophaga canimorsus is described. The six case reports presented here point out the characteristics reported previously: (a) cats are a source of human infection; (b) alcohol abuse is an important risk factor for the development of septicemicCapnocytophaga canimorsus infection; (c) septicemic infection often manifests with disseminated intravascular consumption coagulopathy or purpura; and (d) some cases of septicemia in humans result from pets that lick skin ulcers.     

Clinical, pathogenetic, and laboratory features of Capnocytophaga infections

Granulocytopenia and oral mucosal defects have been reported to be important predisposing factors to recently recognized cases of Capnocytophaga septicemia. The authors call attention to an apparent preponderance of these cases in the pediatric age group and emphasize laboratory features which they have found helpful in the diagnosis of Capnocytophaga infections. Thirteen patients with Capnocytophaga infections were seen during a seven-year period. Seven of these patients had Capnocytophaga bacteremia. Six of seven bacteremic patients were granulocytopenic, six had oral mucosal defects, and three died. Five of the seven bacteremic patients were younger than 20 years of age. This represents a disproportionate distribution of cases in the pediatric age group within the author's institution, because 43% of blood culture specimens submitted to their microbiology laboratory are obtained from pediatric patients. This observation is supported by a review of the reported cases of Capnocytophaga septicemia in which 7 of 12 patients were younger than 20 years of age. Because Capnocytophaga may superficially resemble the more commonly isolated Fusobacterium nucleatum, distinguishing features for laboratory identification are discussed.     

Failure of teicoplanin therapy in two neutropenic patients with staphylococcal septicemia who recovered after administration of vancomycin

A report is given on two neutropenic patients with staphylococcal septicemia caused byStaphylococcus haemolyticus andStaphylococcus aureus (both strains methicillin-resistant) who failed to respond to therapy with teicoplanin. Both strains were resistant to teicoplanin (MIC 16 and 8 mg/l respectively), but remained sensitive to vancomycin (MIC 2 and 4 mg/l respectively). Replacement of teicoplanin with vancomycin led to full recovery of both patients and their discharge from hospital. These two cases emphasize the importance of clinical and microbiological monitoring of patients with staphylococcal septicemia, even when glycopeptides are used for treatment.     

Septicemia secondary to urinary tract infection with colony counts less than 10(5) CFU/mL

This study evaluates the importance of low-colony-count bacteriuria (less than 10(5) CFU/mL) in septicemia originating from urinary tract infections. In a 14-month period, 260 episodes of septicemia occurred. No clinical or microbiologic evidence for a source other than the urinary tract was evident in 68 (26.2%) cases. Of these 68 patients, 13 (19.1%) had colony counts less than 10(5) CFU/mL, and 6 of the 13 had colony counts less than 10(4) CFU/mL. Nine of the infections were community acquired and four were nosocomial. None of the nosocomial cases were associated with an indwelling catheter; four of the 13 patients were receiving chemotherapy and/or steroid therapy. These data support the thesis that some cases of septicemia in patients other than acutely dysuric women, can be caused by UTIs with low colony counts.     

Four cases of shigella septicemia in Israel

Four cases of shigella septicemia are presented. In two children infection was caused byShigella flexneri and in two adults, who had underlying diseases which caused immunosuppression, byShigella sonnei andShigella schmitzi. All four patients responded to intravenous antibiotic therapy. In one patient the organism persisted in the stool, but was eliminated after oral administration of chloramphenicol. Shigella septicemia is not uncommon and blood cultures should be obtained in suspected cases.     

Capnocytophaga canimorsus sp. nov. (formerly CDC group DF-2), a cause of septicemia following dog bite, and C. cynodegmi sp. nov., a cause of localized wound infection following dog bite

CDC group DF-2 is the vernacular name given to a slow-growing gram-negative bacterium that causes septicemia and meningitis in humans. Infections frequently (one-third of cases) occur following dog bites or close contact with dogs or occasionally with cats. Splenectomy and alcoholism appear to be strong predisposing factors for DF-2 infection. In addition to 150 DF-2 strains received for identification, we received 9 DF-2-like strains; 6 were isolated from wound or eye infections, 3 of which were associated with dog bites and 1 of which was associated with a cat scratch, and 3 were isolated from dog mouths. The major characteristics of DF-2 include production of acid but no gas from lactose and maltose and usually D-glucose; positive reactions for oxidase, catalase, arginine dihydrolase, gliding motility, and o-nitrophenyl-beta-D-galactopyranoside; growth enhanced by serum and by incubation in a candle jar atmosphere; and negative reactions for sucrose, raffinose, inulin, melibiose, nitrate reduction, indole, and growth on MacConkey agar. DF-2-like strains had the same characteristics, except that acid was formed from sucrose, raffinose, inulin, and melibiose. By the hydroxyapatite method, DNAs from 12 DF-2 strains were 88% related in 60 degrees C reactions and 84% related in 75 degrees C reactions. Related sequences contained 0.5 to 1.5% unpaired bases (divergence). Three DF-2-like strains were 73 to 80% related at 60 degrees C (with 2.0 to 2.5% divergence) and 68 to 75% related at 75 degrees C. The relatedness of DF-2 and DF-2-like strains was 19 to 31% at 60 degrees Celsius and 13 to 19% at 75 degrees Celsius. The relatedness of DF-2 and DF-2-like strains to Capnocytophaga species was 4 to 7%. The DNA relatedness date indicate that eh DF-2 and the DF-2-like strains are separate, previously undescribed species. Both groups are phenotypically and genetically distinct from Capnocytophaga species, although they do share several characteristics with Capnocytophaga species, including cellular morphology, gliding motility, cellular fatty acid composition, enhancement of growth in a candle jar atmosphere, and G+C content. The new species differ from Capnocytophaga species by their positive oxidase and catalase reactions. We chose to avoid creating a new genus and proposed the names Capnocytophaga canimorsus sp. nov. for group DF-2 and C. cynodegmi sp. nov. for the DF-2-like strains.     

Piperacillin/tazobactam/amikacin versus piperacillin/amikacin/teicoplanin in the empirical treatment of neutropenic patients

A prospective randomized trial was performed to compare the efficacy of a regimen containing a glycopeptide versus one containing a beta-lactamase inhibitor in the treatment of febrile episodes in neutropenic patients. Fifty-eight patients received piperacillin/amikacin/teicoplanin (group 1) and 56 received piperacillin/amikacin/tazobactam (group 2). In the case of persistence of fever without microbiological documentation of the cause, teicoplanin was also given empirically in group 2 on day 4, and amphotericin B in both groups on day 6. In 114 evaluable febrile episodes, the rate of success without modification of therapy was 60 % in patients on piperacillin/amikacin/teicoplanin and 41 % in patients on piperacillin/amikacin/tazobactam (p<0.03). Eleven of 34 patients in the latter group who failed to improve eventually responded upon addition of teicoplanin. Ten and nine patients in group 1 and group 2 respectively required the addition of amphotericin B for definite improvement. There were 14 episodes of gram-positive septicemia in each group: the response rate was 100 % in group 1 and 43 % in group 2. Three episodes of gram-negative breakthrough septicemia occurred in group 1 versus no cases in group 2 (p=0.1). Three deaths occurred in each group. Piperacillin/amikacin/tazobactam may be as efficacious as piperacillin/amikacin/teicoplanin in the treatment of febrile neutropenic patients provided the regimen is modified (usually by addition of teicoplanin) in unresponsive cases.     

Meningitis due to Capnocytophaga canimorsus with misleading initial digestive symptom

We set out a case of Capnocytophaga canimorsus septicemia complicated by a meningitis in a chronic alcoholic male pensioner. The Capnocytophaga canimorsus bacterium contaminated the patient after his dog licked little varicose wounds. Initial symptoms led to a digestive infectious syndrome. Capnocytophaga canimorsus grows more slowly than usual bacteria and appeals to a bacteriological deductive reflection which is provided in this article for its identification in a general hospital. In order not to lose time with that infection which can be lethal, we describe the patient's ground, clinical signs which can be expected and we propose a probabilistic antibiotic therapy while waiting for the laboratory diagnosis.     

Rhodococcus equi infection in non-HIV-infected patients. Two case reports and review

Objective: To review two recent cases in HIV-negative subjects in the light of literature reports (52 patients without HIV infection till 1994).
Method: Epidemiology (animal contacts, risk factors, year, country), clinical presentation, diagnostic methods (X-ray, tomography, microbiological techniques), therapeutic approach (antibiotics, surgery) and outcome were evaluated on the basis of clinical literature reports.
Results: Tumors constituted an important predisposing factor and less frequently hepatobiliary pathology, rheumatologic diseases, iatrogenic causes, psychiatric pathology and trauma. Exposure to animals was reported by 55% of the patients. Pneumonia and pleurisy, without preferential localization, were detected in 50% of the patients. Etiologic diagnosis was usually obtained after an invasive collection. Combined medical therapy and surgery were required by 27.8% of the patients, and 16.7% of the patients died.
Conclusions: In recent years the number of Rhodococcus equi cases has been rising also in HIV-negative patients. The infection is ubiquitous. Accurate diagnosis and the prompt selection of the most appropriate therapy depend on close cooperation between clinicians and microbiologists.     

Waterhouse-Friderichsen syndrome secondary to Capnocytophaga canimorsus septicemia and demonstration of bacteremia by peripheral blood smear

Waterhouse-Friderichsen syndrome caused by Capnocytophaga canimorsus septicemia was fatal in a previously healthy 47-year-old woman. The patient died suddenly in less than 12 hours after presentation, in spite of supportive measures, including ventilation, antibiotic coverage, pressor therapy, and multiple transfusions of blood products. The diagnosis of infection due to an unusual organism was suspected earlier in the course of management after review of the peripheral blood smear. The importance of the findings in the blood smear and their correlation with infection due to this organism are discussed.     

Use of cefotaxime in severe infections in newborn infants

Twenty-seven septicemia, 2 urinary tract infections and 2 meningitis were treated with Cefotaxime. The pathogenic organisms were most often entero-bacteria (16 E. coli, 2 Klebsiella, 2 Enterobacter cloacae, 1 Proteus, 1 Acinetobacter); sometimes they were Streptococcus (5 Streptococcus D, 3 Streptococcus B, 1 Streptococcus Salivarius). Cefotaxime was given alone to 16 patients, in association to an aminoglycoside in 15 cases. It was administered by infusion over 30 minutes every 8 hours in a daily dose of 150 mg/kg (during 10 days in case of septicemia and during 18 days if it was a meningitis). A clinical and bacteriological success was obtained in 86% of the 22 cases caused by Enterobacteria, in one of the 5 septicemia due to Streptococcus D and in the 3 infections caused by Streptococcus B. It may be concluded from these results that cefotaxime may be used in neonate infection due to a Gram-. But when a Listeria or a Streptococcus D is discovered the ampicillin classically prescribed must be maintained.     

Fungal osteoarticular infections in patients treated at a comprehensive cancer centre: a 10-year retrospective review

This study reviewed retrospectively the clinical characteristics of 28 cancer patients with fungal osteoarticular infections (FOAIs) between 1995 and 2005. Most patients (26; 93%) had haematological malignancies (19 had leukaemia); half (14) were allogeneic stem-cell transplant recipients. Twelve patients (43%) had severe neutropenia (< or = 100/mm3) with a mean duration of 65 days (range 10-500 days), and ten (36%) patients had received a significant dose of corticosteroids. Most (19; 68%) FOAIs were caused by contiguous extension, while nine (32%) were associated with haematogenous spread. Pain, joint instability and local drainage were seen in 28 (100%), six (21%), and seven (25%) patients, respectively. Sixteen (57%) patients had symptoms for < 1 month. The sinuses (ten; 36%) and the vertebral spine (six; 21%) were the most common sites involved. Moulds were the predominant pathogens: Aspergillus fumigatus (two); non-fumigatus Aspergillus spp. (eight); non-specified Aspergillus spp. (three); Fusarium spp. (six); Zygomycetes (five); Scedosporium apiospermum (two); and Exserohilum sp. (one). Candida was the causative pathogen in four cases (including two cases of mixed FOAIs). Arthritis and post-operative FOAIs were both uncommon manifestations, occurring in two patients each. All patients received systemic antifungal therapy (combinations in 20 cases), and 19 cases underwent adjunctive surgery. The crude mortality rates (at 12 weeks) were 44% (9/20) in the patients who underwent surgery and antifungal therapy vs. 33% (2/6) in patients who received antifungal therapy alone (p not significant). FOAI is a rare, yet severe, manifestation of localised or systemic mycoses, caused predominantly by moulds, and is seen typically in patients with haematological malignancies.     

Enterococcal septicemia in patients with hematological malignancies

Thirty-six cases of enterococcal septicemia in patients with hematological malignancies were reviewed retrospectively and categorized according to their clinical significance using strict previously described definitions. Overall, most of the infected patients were males (77 %), had acute leukemia (64 %), had recently received cytotoxic drug therapy (86 %), were granulocytopenic at the onset of septicemia (77 %), and acquired the infection during hospitalization (77 %). The source of septicemia was unknown in 18 (50 %) patients, intestinal in 15 (42 %) and intravascular in three (8 %). Mortality was 19 % among 21 inpatients who had clinically significant septicemia and 30 % among patients with septicemia of uncertain clinical significance. The fatal outcome could be definitively attributed to enterococcal septicemia in only one of the nine inpatients who died. Clinically significant septicemia appeared somewhat more frequently to be polymicrobial (p=0.06), whereas septicemia of unknown significance presented more frequently as breakthrough septicemia (p=0.013). Unless associated with intravascular infection, enterococcal septicemia in patients with hematological malignancies seems to represent a marker of cytotoxic drug damage of the intestinal mucosa rather than a truly invasive infection.     

Human cytomegalovirus, human herpesvirus-6 and human herpesvirus-7 in neutropenic patients with fever of unknown origin

Objective  To investigate the appearance of cytomegalovirus (CMV) DNA, human herpesvirus-6 (HHV-6) DNA and human herpesvirus-7 (HHV-7) DNA in plasma as a sign of reactivation and possible causes of fever of unknown origin (FUO) during neutropenia.
Methods  From 134 patients with febrile neutropenia following cytotoxic chemotherapy during the years 1996–2000, 20 severely neutropenic patients (granulocyte count < 0.1 × 10⁹/L) were selected. Ten were patients with bacteremia and ten were patients with FUO. Five samples from each patient were selected at the start of chemotherapy, at the time of blood culture and fever, after 24 and 48 hours of fever, and, finally, after two to three days without fever. Virus DNA was detected by real-time quantitative and nested polymerase chain reaction (PCR).
Results  CMV-DNA was detected in two out of ten FUO-patients in all samples drawn during fever. From another FUO and during two bacteremia episodes, CMV-DNA was detected after 48 hours of fever. DNA from HHV-6 and HHV-7 was not detected in any of the 20 febrile episodes.
Conclusions  HHV-6 and HHV-7 as a possible explanation for FUO in severely neutropenic patients treated with cytotoxic chemotherapy seems not be very likely. However, CMV was identified in 5/20 patients and the febrile episodes in the two FUO-patients with constant DNA-emia may have been caused by a reactivation of CMV. This implies that CMV infection can be expected not only in transplant patients but also in chemotherapy-treated neutropenic patients.     

Initial antibacterial prophylaxis after bone marrow allograft. Pilot study with systemic vancomycin

In 22 consecutive patients treated by allogenic bone marrow transplantation, the authors report their experience in complete gastrointestinal decontamination and prophylactic systemic vancomycin. Neither septicemia from the low digestive tract nor with Gram positive is noticed. A child developed septicemia with Capnocytophaga ochracea, resistant to vancomycin. There is no infectious death in this study and no significative toxicity is reported.     

Serum levels of ciprofloxacin after single oral doses in patients with septicemia

Ciprofloxacin serum levels were measured after administration of the drug to 36 patients with septicemia (at least one positive blood culture) who were able to take oral medication. Patients were randomly allocated to receive ciprofloxacin 500 mg p.o. (n=21) or 200 mg i.v. over 30 min (n=15). A first dose was administered 18–30 h after the last positive blood culture (day 1), and a second dose four days later (day 5) in some patients. In addition to ciprofloxacin, standard antibiotics were administered. Organisms isolated wereEscherichia coli (15), other gram-negative bacteria (6),Streptococcus pneumoniae (7),Staphylococcus aureus (2), and other gram-positive bacteria (6). None of the patients vomited. Ciprofloxacin serum concentrations 1 h after oral administration were in the range 0.09–2.32 mg/l, and 2 h after administration in the range 0.5–7.27 mg/l. The average terminal half-life was 8.6 h. In individual patients serum concentrations and area-under-the-curve values were compared. Poor correlation was found between values measured on day 1 and day 5 after oral administration, whereas the correlation was excellent after i.v. administration. Serum levels 2 h after oral administration were 30–900 times the MICs for the gram-negative organisms, but were in the range of the MICs for the gram-positive organisms in some cases. In conclusion, ciprofloxacin serum levels are difficult to predict in septicemia patients after oral administration, but probably suffice to treat infections caused by gram-negative organisms.     

Efficacy of injectable ofloxacin in treating septicemia. Multicenter study

To evaluate the efficacy and safety of parenteral ofloxacin in the treatment of septicemia, a multicenter study was carried out in 88 patients, 53 men and 35 women, hospitalized either in intensive care units (41 patients) or in medical wards (47 patients). Ofloxacin was administered at a dose of 200 mg every 12 hours for a mean duration of ten days. Ofloxacin was administered as single agent to 62 patients. A clinical cure was obtained in 81 patients. Death occurred in 3 cases, relapse in 2, superinfection in one, and persistence of the infecting organism in another case (with acquired resistance to ofloxacin). 89 of the 94 isolated organisms (75% Gram negative-bacilli and 20% staphylococci) were eradicated. The adverse effects were rare, mild or moderate in severity, and always reversible. We conclude that I.V. ofloxacin is efficacious and safe in the treatment of septicemia due to Gram-negative bacilli or staphylococci.     

Evaluation of the use of ofloxacin in the treatment of various infections

We investigated the clinical efficiency and safety of ofloxacin, a new fluoroquinolone, for the treatment of various documented bacterial infections in 26 patients (10 females, 16 males) aged 17 to 84 years. Ofloxacin monotherapy was given orally in a dose of 200 mg twice (25) or three times (1) a day. Antibiotic levels and serum bactericidal activity were measured using a microbiological method on the second and sixth days, before and 2 and 6 hours after a single dose. The infectious episode treated was enterocolitis in 7 cases (5 Shigella, 2 Salmonella), Salmonella septicemia in 9 (7 typhoid fevers and 2 Salmonella minor infections), chronic osteoarthritis in 3 (1 E. coli, 2 S. aureus + P. aeruginosa), a soft tissue infection in 3 (2 S. aureus, 1 E. coli), acute pleuropneumonia in 2 (2 Klebsiella pneumoniae), pyelonephritis with bacteremia in 1 (Klebsiella pneumoniae), and pneumococcal pneumonia with septicemia in 1. Mean duration of therapy was ten days for 23 patients (range 7 to 30 days). The three patients with osteoarthritis were treated for 35, 95 and 270 days respectively. 24 patients recovered free of sequelae or germ carriage. Treatment failed in 1 case of chronic osteitis (S. aureus + P. aeruginosa) and in 1 staphylococcal soft tissue infection. No adverse reactions were observed except a slight increase in transaminases in 3 patients. Peak and through serum ofloxacin levels were 3.70 micrograms/ml and 0.95 micrograms/ml respectively on the second day and 3.25 micrograms/ml and 0.80 microgram/ml respectively on the sixth day.(ABSTRACT TRUNCATED AT 250 WORDS)     

A cluster of seven cases ofClostridium tertium septicemia in neutropenic patients

A cluster of seven febrile and severely neutropenic patients who developedClostridium tertium septicemia during a 13-month period is described. The patients had received third generation cephalosporins for 7 to 13 days (mean 9 days) at the timeClostridium tertium was isolated from blood cultures. Two patients had perirectal and one patient pericaecal cellulitis. The organism was also isolated from bronchial secretions in one patient. No patient had diarrhea. Five of six strains tested were resistant to clindamycin (MIC 2–8 µg/ml), and six of seven strains moderately resistant to penicillin (MIC 1–4 µg/ml). In one patientClostridium tertium grew from blood cultures although metronidazole had been administered for two days. Six patients recovered on antibiotic therapy. In view of the unusual susceptibility pattern ofClostridium tertium, an accurate diagnosis of infection with this organism is important for the choice of an appropriate antimicrobial treatment.     

High risk of streptococcal septicemia after high dose cytosine arabinoside treatment for acute myelogenous leukemia

Summary Twenty-nine adult patients with acute myelogenous leukemia AML who received 40 treatment courses with high dose cytosine arabinoside (HD-A), alone or combined with other cytotoxic drugs, for remission induction (RI) or postremission intensive consolidation (IC) were retrospectively analysed for types and severity of infectious complications. In this paper, we report the unusually high rate of streptococcal septicemia in our patients. Of 13 bacteremic infections in a total of 45 infectious episodes, 10 were caused by streptococci (9 viridans streptococci, 1 group B hemolytic streptococcus). Three of them were lethal. After reviewing all documented cases of streptococcal septicemia in the same study period, four additional cases among adult patients with AML were identified. Three of them have had antileukemic chemotherapy without HD-A, while one have had HD-A as a conditioning regimen for bone marrow transplantation. Only three cases were documented to occur in adult patients with AML. Patients treated with HD-A for RI or IC had a significantly lower risk of streptococcal septicemia during previous chemotherapy-associated febrile neutropenic episodes (1/55 vs 10/45;P=0.01). Neither prophylactic regimens including trimethoprim-sulfamethoxazole nor those without it were effective in preventing streptococcal septicemia. Further studies are needed to confirm these data before the value of additional or alternative prophylactic antibiotics is proven necessary.Abbreviations AML Acute myelogenous leukemia - HD-A High dose cytosine arabinoside - IC Postremission intensive consolidation - RI Remission induction