An autopsy study of systemic fungal infections in patients with hematologic malignancies

The aim of this study was to determine the incidence of fungal infections detected on autopsy in a group of 40 patients with hematologic malignancies treated with intensive chemotherapy or bone marrow transplantation, and to evaluate the risk factors for fungal infections. A control group included 38 patients with nonhematologic diseases and without granulocytopenia but with at least one of the known risk factors for fungal infections. Standard histopathological and microbiological methods were used. A higher incidence of invasive fungal infections was found in patients with hematologic malignancies as compared to the control group (p<0.01). The predominant causes of fungal infections wereCandida albicans andAspergillus spp. The incidence of fungal infections caused byAspergillus was higher (p<0.05) in patients with hematologic malignancies than in the control group. The independent risk factors for fungal infections were fungal colonization, number of antibiotics and duration of antibiotic therapy, duration of fever and skin rash. A higher proportion of fungal infections was diagnosed on autopsy than during the patients' life (p<0.01).     

Fluconazole treatment of Candidal infections caused by non-Albicans Candida species

Fluconazole is an effective alternative to amphotericin B for the treatment of serious infections caused byCandida albicans. Through a literature survey of candidal infections caused by non-albicans Candida spp., 43 cases treated with fluconazole were found. The most common causative organisms wereCandida parapsilosis (14 patients),Candida glabrata (12 patients), andCandida tropicalis (11 patients). The dose of fluconazole varied from 50 to 400 mg daily. The median duration of treatment was 21 days. Overall efficacy was 77%. The efficacy against the various species was 93% forCandida parapsilosis, 50% forCandida glabrata, and 82% forCandida tropicalis. In conclusion, fluconazole is effective against the most commonnonalbicans Candida spp., although higher doses may be required for infections caused byCandida glabrata. Infections caused byCandida krusei should not be treated with fluconazole.     

Nosocomial bacteremia caused byBacillus species

During a six year period, 11 cases of bacteremia caused byBacillus spp. were observed corresponding to 1 % of all bacteremic episodes in our hospital. Most patients had cancer as underlying disease. All cases of positive blood cultures were associated with a clinical syndrome compatible with sepsis including high fever. None of the subsequent deaths could be related to the bacteremia caused byBacillus spp. Four of eight cases ofBacillus subtilis bacteremia were associated with the absorption of an oral preparation containingBacillus subtilis spores, which was administered empirically in some units of the hospital to reduce what was considered to be tubefeeding related diarrhea.Research Associate, Fund for Medical Scientific Research, Belgium.     

Evaluation of serological methods in the diagnosis ofChlamydia pneumoniae pneumonia during an epidemic in Finland

A complement fixation (CF) test, a micro-immunofluorescence (micro-IF) test and an enzyme immunoassay (EIA) using Re-lipopolysaccharide as antigen were compared in the diagnosis of chlamydial infection in 136 mainly elderly patients hospitalized with community-acquired pneumonia during aChlamydia pneumoniae epidemic in Finland in 1986–1987. Chlamydial pneumonia was diagnosed in 58 (42.6 %) of the 136 pneumonia patients; 44 (75.9 %) of them could be shown by micro-IF to be caused byChlamydia pneumoniae, three byChlamydia psittaci and four byChlamydia spp. Only 5 (11.4 %) of 44 patients withChlamydia pneumoniae pneumonia were IgM-positive, indicating that the majority of cases were reinfections. In this population of mainly elderly patients the CF test was insensitive, being positive in only 6 (10.3 %) of 58 cases of chlamydial pneumonia. The EIA detected 72.4 % of cases and micro-IF 87.9 % of cases (including infections withChlamydia pneumoniae, Chlamydia psittaci andChlamydia spp.). In the EIA 77 % of positive cases were positive in serum samples taken a week apart, whereas the corresponding figure for micro-IF was 50 %. In micro-IF the measurement of IgA antibody levels is recommended and IgM-positive sera should be retested after removal of IgG antibody to avoid false-positive findings due to presence of rheumatoid factor. The collection of a third serum sample, for instance one month after onset, is also recommended, since half of the patients showed a diagnostic response in the micro-IF only in the sera taken one month apart.     

Cryptosporidia in immunocompetent patients with gastroenteritis

In a prospective study Cryptosporidium spp. were detected in nine immunocompetent patients (0.6 %). The frequency was remarkably higher in children in the 0 to 14 year age group (1.6 %), surpassed only by Salmonella spp. and Campylobacter spp. The predominant clinical features were watery diarrhea, abdominal pain, and vomiting. Comparison of the epidemiological data of the patients with those of a control group showed that contact persons with enteritis and drinking of unpasteurized milk were significantly associated with cryptosporidiosis.     

Prospective study ofCandida colonization,use of empiric amphotericin B and development of invasive mycosis in neutropenic patients

The association between colonization withCandida spp., subsequent occurrence of invasive candidiasis and empiric use of amphotericin B was investigated prospectively in 139 neutropenic patients with hematologic malignancies. Treatment with amphotericin B was required in 67 % of patients colonized in multiple non-contiguous body sites (multicolonized) versus 31 % of patients colonized in single or contiguous sites (monocolonized) and in 21 % of non-colonized patients (p=0.0037 and p=0.00026, respectively). Invasive candidiasis was documented in 22.2 % of multicolonized versus 4.8 % of monocolonized patients and in none of the non-colonized patients (p=0.035 and p=0.0036, respectively). Analysis of the spectrum of colonizingCandida spp. showed that multicolonized subjects were colonized with increased frequency byCandida albicans compared to monocolonized subjects, and that the association between multicolonization, invasive candidiasis and amphotericin B usage was statistically significant in patients colonized byCandida albicans but not in patients colonized by otherCandida species. The association betweenCandida multicolonization and the occurrence ofCandida infection seems to be confirmed by a double-blind placebo-controlled study performed in a small subgroup of the multicolonized patients treated with fluconazole.     

Changing trends in etiology of bacteremia in patients with cancer

The present study was conducted to determine trends in the quantitative bacterial load patterns of bacterial bloodstream infections (BSI) caused by various bacteria in patients receiving care at a comprehensive cancer center. Bacterial loads of all consecutive quantitative blood cultures performed during 1998 and 2004 were graded quantitatively. Gram-positive bacteria (GPB) were responsible for the majority of BSI episodes in both years studied: 740 of 1,055 (73%) in 1998 and 820 of 1,025 (82%) in 2004. Compared with GPB infections, a significant proportion of infections caused by Gram-negative bacteria was associated with a high bacterial load (HBL) (11 vs 28% in 1998 and 10 vs 30% in 2004; p<0.001). In 2004, BSI episodes due to non-Pseudomonas non-fermentative GNB (Stenotrophomonas maltophilia and Acinetobacter spp) were significantly associated with a HBL compared to BSI due to Pseudomonas aeruginosa (47 vs 23%; p<0.05); this was not the case in 1998. Conversely, the HBLs commonly associated with BSI due to Staphylococcus aureus (50%) and Streptococcus spp (35%) versus coagulase-negative staphylococci (13%; p<0.0001) during 1998 were not noted during 2004 (22% Staphylococcus aureus, 20% Streptococcus spp, 21% coagulase-negative staphylococci; p>0.5). The spectrum of BSI continues to change and its prognostic implications in cancer patients needs further study.     

Persistent Bacteremia in the Absence of Defined Intravascular Foci: Clinical Significance and Risk Factors

The clinical significance of and the risk factors for persistent bacteremia were assessed in 299 episodes. Persistent bacteremia was defined as at least two positive blood cultures obtained on different calendar days during the same infectious episode. Short-term bacteremia was defined as positive blood cultures solely on the first day of the infectious episode. A total of 4,277 episodes of bloodstream infections were detected, of which 299 episodes (7%) were persistent bacteremia. The following were independent risk factors were for persistent bacteremia: burns, presence of a central vascular catheter, cirrhosis, infections caused by Salmonella spp., polymicrobial infections, and inappropriate empirical antibiotic treatment. Irrespective of the source of infection, the presence of a central vascular catheter was correlated with an increased risk for persistent bacteremia. Mortality among patients with persistent bacteremia was 50%, compared to 35% among patients with short-term bacteremia. Because of the high mortality associated with persistent bacteremia, a thorough search for the source of infection is essential to ensure timely and appropriate therapy.     

Frequency of Isolation of Pathogens from Bloodstream, Nosocomial Pneumonia, Skin and Soft Tissue, and Urinary Tract Infections Occurring in European Patients

 The frequency of isolation of pathogens that cause different types of infections is an important guide for empiric therapy. As part of the SENTRY Antimicrobial Surveillance Program, the frequency of isolation of different bacterial species from bloodstream, nosocomial pneumonia, skin and soft tissue, and urinary tract infections occurring in European patients was determined. A total of 15,704 isolates were collected in 1997 and 1998 from 24 university hospitals in 14 European countries: 9,194 from bloodstream, 2,052 from nosocomial pneumonia, 2,320 from skin and soft tissue, and 2,138 from urinary tract infections. More than 95% of all bacterial infections were caused by only 15 different genera. Staphylococcus spp. and Escherichia spp. accounted for more than 50% of the infectious isolates, with the exception of those obtained from cases of nosocomial pneumonia. In the latter type of infection, isolates belonging to these two genera were responsible for 30% of the infections. An analysis at the individual species level showed that Escherichia coli caused a large proportion of bloodstream and urinary tract infections (20.8% and 49.3% of isolates, respectively). Staphylococcus aureus was the main causative species for nosocomial pneumonia and skin and soft tissue infections (21.5% and 37.4% of isolates, respectively). In addition, Pseudomonas aeruginosa played an important role in all types of infection analyzed.     

Diagnosis of invasive aspergillosis and mucormycosis in immunocompromised patients by seminested PCR assay of tissue samples

Aspergillosis and mucormycosis are the most common mold infections in patients with hematological malignancies. Infections caused by species of the genus Aspergillus and the order Mucorales require different antifungal treatments depending on the in vitro susceptibility of the causative strain. Cultures from biopsy specimens frequently do not grow fungal pathogens, even from histopathologically proven cases of invasive fungal infection. Two seminested PCR assays were evaluated by amplifying DNA of zygomycetes and Aspergillus spp. from organ biopsies of 21 immunocompromised patients. The PCR assays correctly identified five cases of invasive aspergillosis and six cases of mucormycosis. They showed evidence of double mold infection in two cases. Both assays were negative in five negative controls and in two patients with yeast infections. Sequencing of the PCR products was in accordance with culture results in all culture-positive cases. In six patients without positive cultures but with positive histopathology, sequencing suggested a causative organism. Detection of fungal DNA from biopsy specimens allows rapid identification of the causative organism of invasive aspergillosis and mucormycosis. The use of these PCR assays may allow guided antifungal treatment in patients with invasive mold infections.     

Brucellar prosthetic arthritis in a total knee replacement

The infecting pathogens most commonly implicated in prosthetic joint infections are staphylococci, streptococci, and gram-negative rods. Prosthetic infections caused byBrucella spp, are rarely described in the literature. Treatment of prosthetic infections remains complex and controversial, the most accepted course being antibiotic treatment with removal or retention of prosthetic components. The case of a 60-year-old man who developedBrucella septic arthritis of the right knee in a total knee replacement is reported. Conservative treatment using a three-drug therapy was employed, with excellent results.     

Opportunistic fungal infection among cancer patients. A ten-year autopsy study.

A high incidence of opportunistic fungal infections among cancer patients has been a pressing problem confronting clinicians. The fungal infections in 3,278 consecutive autopsies at Thomas Jefferson University Hospital during a ten-year period (1966-1975) were studied. There were 1,204 (36.7%) cancer patients; 85 (7.1%) of these patients had concomitant fungal infections. The incidence was 9.3% during the last five-year period; 5.1% during the first five-year period. Candidiasis was the most frequent fungal infection (52.2%) among these patients, followed by aspergillosis (31.1%), mucormycosis, cryptococcosis, histoplasmosis and nocardiosis. The leukemias and lymphomas were the most frequent malignancies associated with fungal infections. However, in this study, unlike others, the incidences of fungal infection in patients with some solid tumors were also high, especially those in patients with cancers of the colon and pancreas.     

Comparative study of clinical characteristics of neutropenic and non-neutropenic adult cancer patients with bloodstream infections

A total of 399 consecutive episodes of bloodstream infections in adult patients with haematologic malignancies and solid tumours were evaluated prospectively over a 26-month period, with the aim of determining the clinical characteristics and the microbiological profile of the patients relative to neutrophil count. The overall 30-day mortality rate was 32% (35% in non-neutropenic patients vs. 26% in neutropenic patients, p=0.05). Main diagnoses were solid tumours (33%) and lymphoma (29%). Most of the episodes of bloodstream infection (58%) occurred in non-neutropenic patients. Acute leukaemia and bone marrow transplantation predominated in the neutropenic group. Non-neutropenic patients tended to be older and to have a higher frequency of solid tumours and advanced or uncontrolled diseases. Indwelling central venous catheters were present in 51% of the episodes, with a predominance of long-term catheters in neutropenic haematologic patients. Concomitant infections were observed more frequently in non-neutropenic patients. There were 1,040 noninfectious comorbid conditions, most of which were present in non-neutropenic patients. The causative pathogens were predominantly gram-negative bacilli (56%). Escherichia coli and Klebsiella pneumoniae were isolated more frequently from neutropenic patients, while Staphylococcus aureus and Acinetobacter spp. were more frequent in non-neutropenic patients. Seventy-four percent of the episodes of candidaemia occurred in patients with central venous catheters, with non-albicans strains predominating. The results of this study highlight the heterogeneity of cancer patients with bloodstream infections and the value of stratifying risk factors and aetiologic agents according to neutrophil count. This work was presented in part at the 7th International Symposium on Febrile Neutropenia, 27–29 January 2005, Seville, Spain.     

Use of 16S rRNA gene sequencing to identifyLactobacillus casei in septicaemia secondary to a paraprosthetic enteric fistula

Human infections caused byLactobacillus spp. are rarely reported in the literature. Underlying conditions are frequently reported, and identification of lactobacilli to the species level remains rare. A case ofLactobacillus casei septicaemia secondary to a vascular graft infection is reported. The 16S rRNA sequencing technique was used to definitively identifyLactobacillus casei.     

Microbiology of folliculitis: a histological study of 39 cases

Folliculitis is a common inflammatory skin syndrome. Several microbial organisms have been put forward as causative agents, but few studies visualized microbes directly in inflamed hair follicles. This retrospective study investigated bacterial and fungal colonization of inflamed hair follicles in patients with clinically diagnosed non‐infectious folliculitis. Skin biopsies from 39 folliculitis patients and 27 controls were screened by fluorescence in situ hybridization (FISH) using broad‐range bacterial and fungal probes and by immunofluorescence microscopy using a monoclonal antibody towards Gram‐positive bacteria. Specific monoclonal and polyclonal antibodies towards Staphylococcus spp. and Propionibacterium acnes were applied for further species identification. Inflamed follicles were associated with bacterial colonization in 10 samples (26%) and fungal colonization in three samples (8%). Staphylococcus spp. were observed in inflamed follicles in seven samples (18%). Two samples were positive for P. acnes, which were identified as either type II or type IB/type III. Both Staphylococcus spp. and P. acnes were seen in macrocolonies/biofilm structures. In conclusion, one‐third of patients with clinically diagnosed, non‐infectious folliculitis exhibited microbial colonization with predominance of Staphylococcus spp.     

Nosocomial fungal infections: epidemiology, diagnosis, and treatment.

Invasive fungal infections are increasingly common in the nosocomial setting. Furthermore, because risk factors for these infections continue to increase in frequency, it is likely that nosocomial fungal infections will continue to increase in frequency in the coming decades. The predominant nosocomial fungal pathogens include Candida spp., Aspergillus spp., Mucorales, Fusarium spp., and other molds, including Scedosporium spp. These infections are difficult to diagnose and cause high morbidity and mortality despite antifungal therapy. Early initiation of effective antifungal therapy and reversal of underlying host defects remain the cornerstones of treatment for nosocomial fungal infections. In recent years, new antifungal agents have become available, resulting in a change in standard of care for many of these infections. Nevertheless, the mortality of nosocomial fungal infections remains high, and new therapeutic and preventative strategies are needed.     

<Emphasis Type="Italic">Citrobacter</Emphasis> infections in a general hospital: characteristics and outcomes

In this investigation, we sought to investigate the characteristics of Citrobacter spp. infections. A retrospective cohort study in a 700-bed, tertiary care, university hospital was carried out during the period from June 1994 to January 2006. Seventy-eight patients (70 adults) with Citrobacter spp. isolates were identified. C. freundii was more common (71.8%), followed by C. koseri (23.1%) and C. braakii (3.8%). The most common associated clinical syndromes were urinary tract infections (52.6% of cases, including eight cases of asymptomatic bacteriuria), as well as intra-abdominal (14.1%), surgical site (7.7%), skin and soft tissue (6.4%), and respiratory tract infections (6.4%). In 29.5% of patients, Citrobacter spp. isolates were associated to polymicrobial infections, principally at sites other than the urinary tract. Antibiograms of 38 consecutive Citrobacter spp. isolates (29 C. freundii) were available. Most active agents were colistin (100%), fosfomycin (100%), imipenem (97.4%), gentamicin (89.5%), nitrofurantoin (89.5%), ciprofloxacin (80.6%), and cefepime (73.7%). Most patients (82.1%) had at least one underlying illness. Combination antimicrobial therapy was administered in 28.2% of cases. One patient died during hospitalization. The length of hospital stay was longer in patients with polymicrobial compared to monomicrobial infections (23 versus 13 days, respectively, p = 0.02). The isolation of Citrobacter species, although rather infrequent, was clinically relevant in the great majority of cases. Further attention should be paid to these pathogens. Funding  None.     

Efficacy of fluconazole in the treatment of systemic fungal infections

The efficacy of fluconazole in the treatment of systemic fungal infections was evaluated in an open non-comparative trial. A total of 48 patients with proven or suspected fungal infections were enrolled in 40 of whom efficacy was evaluable.Candida albicans accounted for 90 % of the infections.Candida parapsilosis, Candida glabrata, Histoplasma capsulatum andAspergillus fumigatus caused the infection in one case each. Fluconazole was administered at a dosage of 200–400 mg daily for a mean duration of 15 days. Fluconazole treatment was successful in 53 % of the patients. In patients with proven or probableCandida albicans infections a clinical and mycological response was achieved in 62 % and 65 %, respectively. In 11 patients elevation of liver enzymes was considered to be possibly related to fluconazole treatment; modification of treatment was not necessary in any case. Fluconazole was found to be a well tolerated and effective agent for the treatment of systemicCandida albicans infections.     

Use of Voriconazole to Successfully Treat Disseminated <Emphasis Type="Italic">Trichosporon asahii</Emphasis> Infection in a Patient with Acute Myeloid Leukaemia

Trichosporon spp. is an emerging fungal pathogen in immunocompromised hosts, and disseminated infection is often fatal in neutropenic patients. Reported here is a case of disseminated infection in a neutropenic patient with acute leukaemia. After failure of amphotericin B and fluconazole therapy, the course of infection dramatically improved with voriconazole treatment. A literature search revealed 69 additional cases of disseminated Trichosporon spp. infections in neutropenic patients, and these are also reviewed. Clinical symptoms that suggest infection include fever, disseminated papulopustular cutaneous lesions and pulmonary involvement. Despite treatment with antifungal agents (amphotericin B, fluconazole), 78% of patients died. Voriconazole may represent a promising therapy for this life-threatening infection. Electronic Publication     

Prospective study of renal transplant infections in 50 consecutive patients

A prospective study of the frequency, timing, etiology and risk factors of infections in renal transplant recipients during the first year after transplantation was conducted in 50 consecutive patients. Neither prophylaxis with trimethoprim-sulfamethoxazole nor antiviral prophylaxis was administered. Two hundred twenty-eight episodes of infection were registered (4.5 per patient), 19 of which were severe. Forty-seven percent of all infectious episodes occurred during the first two months after transplantation. The more frequent infections were bacterial (64 %), viral (22 %) and fungal (11 %).Escherichia coli was the most common agent isolated (n=36), followed by cytomegalovirus (n=32). Urinary tract infections were most common (n=144), especially asymptomatic bacteriuria (n=106). Surgical reintervention and the use of antilymphocytic globulins were associated with a higher frequency of severe infections (p<0.05), and invasive candidiasis was associated with allograft loss (p<0.03). Annual survival rates of patients and allografts were 100 % and 94 %, respectively. The frequency of mild infections was higher than that observed in other studies using bacterial or viral prophylaxis. Nevertheless, the number of severe infections and the survival rates of patients and allografts were similar to those reported in previous studies.