Epidemiology of Visceral Mycoses: Analysis of Data in Annual of the Pathological Autopsy Cases in Japan

The data on visceral mycoses that had been reported in the Annual of the Pathological Autopsy Cases in Japan from 1969 to 1994 by the Japanese Society of Pathology were analyzed epidemiologically. The frequency of visceral mycoses among the annual total number of pathological autopsy cases increased noticeably from 1.60% in 1969 to a peak of 4.66% in 1990. Among them, the incidences of candidiasis and aspergillosis increased the most. After 1990, however, the frequency of visceral mycoses decreased gradually. Until 1989, the predominant causative agent was Candida, followed in order by Aspergillus and Cryptococcus. Although the rate of candidiasis decreased by degrees from 1990, the rate of aspergillosis increased up to and then surpassed that of candidiasis in 1991. Leukemia was the major disease underlying the visceral mycoses, followed by solid cancers and other blood and hematopoietic system diseases. Severe mycotic infection has increased over the reported 25-year period, from 6.6% of the total visceral mycosis cases in 1969 to 71% in 1994. The reasons for this decrease of candidiasis combined with an increase of aspergillosis or of severe mycotic infection might be that (i) nonsevere (not disseminated) infections were excluded from the case totals, since they have become controllable by antifungal drugs such as fluconazole, but (ii) the available antifungal drugs were not efficacious against severe infections such as pulmonary aspergillosis, and (iii) the number of patients living longer in an immunocompromised state had increased because of developments in chemotherapy and progress in medical care.     

The first case of Wickerhamomyces anomalus fungemia in Iran in an immuneodeficient child,a review on the literature

The incidence of invasive candidiasis in pediatric patients is increasing and is associated with significant morbidity and mortality. C. pelliculosa has been rarely reported as a human pathogen, however, it has been associated with serious nosocomial infections and clonal outbreaks with poor clinical outcomes in immunocompromised children were reported. Here, we describe the first case of candidemia due to Candida pelliculosa in a 5-year-old immunocompromised male suffered from Griscelli syndrome with hemophagocytic syndrome hospitalized in the pediatric intensive care unit (PICU), Tehran, Iran. In addition, the history of reported cases or case-series due to C. pelliculosa is reviewed.     

Is it time to reconsider initial antibiotic treatment strategies for severe urinary tract infections in Europe?

Until recently, most reported cases of bacteraemia caused by multidrug-resistant strains of Enterobacteriacae producing an extended-spectrum beta-lactamase (ESBL) in Europe have been nosocomial in origin. However, increasing numbers of reports of community-acquired bacteraemia and urinary tract infection caused by ESBL-producing microorganisms suggest that the geographical origin of patients should be taken into account as a risk-factor for possible ESBL production. Early identification of patients at high-risk of infection with ESBL-producing microorganisms, based on their geographical origin and travel history, should help to optimise initial antibiotic treatment strategies for severe urinary tract infections in Europe.     

Nosocomial infections due to rotavirus and respiratory syncytial virus in pediatric wards: a 2-year study

Rotavirus and respiratory syncytial virus (RSV) infections represent up to 30% of the totality of nosocomial infections in paediatric wards. We studied the importance of these infections in the paediatric wards of the University Hospital Center of Poitiers, France, from October 1996 to September 1998. We defined as nosocomial an infection acquired after 3 days of hospitalization for rotavirus and after 7 days for RSV. The 274 cases of children presenting rotavirus gastroenteritis or RSV infection within this period were studied. Rotavirus was detected in stools by using an agglutination test and RSV was diagnosed in nasopharyngeal aspirations by direct examination with an immunofluorescence assay (IFA), cell culture and serotyping with IFA. We noted 50 rotavirus and 224 RSV infections, with a first epidemic of RSV subgroup B (49.5%) and a second epidemic of subgroup A (44.9%). 19 (38%) were rotavirus nosocomial infections and 5 (2.2%) were RSV nosocomial infections. The majority of the nosocomial infections occurred before the age of one year and particularly before the age of 6 months (42.2% for rotavirus, 60% for RSV). In comparison to community-acquired infections, children with rotavirus nosocomial infections were younger (9 months versus 12.5 months) which was the opposite for RSV nosocomial infections (10.8 months versus 6.5 months). The sex-ratio of children with community-acquired infections was 2.1 that was not reported in nosocomial infections. The length of stay in hospital was always longer in nosocomial infections (11.7 days versus 3.6 days for rotavirus; 38.8 days versus 4.8 days for RSV). Diarrhea (p = 0.007) and vomiting (p = 0.013) for enteric infections and wheezing (p = 0.02) for respiratory infections were more often observed in community-acquired infections. This study emphasizes the frequency and the consequences of rotavirus and RSV nosocomial infections in paediatric wards and the importance of the hygienic rules to prevent these infections.     

Burden of serious fungal infections in Guatemala

Guatemala is a developing country in Central America with a high burden of HIV and endemic fungal infections; we attempted to estimate the burden of serious fungal infections for the country. A full literature search was done to identify epidemiology papers reporting fungal infections from Guatemala. We used specific populations at risk and fungal infection frequencies in the population to estimate national rates. The population of Guatemala in 2013 was 15.4 million; 40% were younger than 15 and 6.2% older than 60. There are an estimated 53,000 adults with HIV infection, in 2015, most presenting late. The estimated cases of opportunistic fungal infections were: 705 cases of disseminated histoplasmosis, 408 cases of cryptococcal meningitis, 816 cases of Pneumocystis pneumonia, 16,695 cases of oral candidiasis, and 4,505 cases of esophageal candidiasis. In the general population, an estimated 5,568 adult asthmatics have allergic bronchopulmonary aspergillosis (ABPA) based on a 2.42% prevalence of asthma and a 2.5% ABPA proportion. Amongst 2,452 pulmonary tuberculosis patients, we estimated a prevalence of 495 for chronic pulmonary aspergillosis in this group, and 1,484 for all conditions. An estimated 232,357 cases of recurrent vulvovaginal candidiasis is likely. Overall, 1.7% of the population are affected by these conditions. The true fungal infection burden in Guatemala is unknown. Tools and training for improved diagnosis are needed. Additional research on prevalence is needed to employ public health measures towards treatment and improving the reported data of fungal diseases.     

Acute disseminated candidiasis with skin lesions: a systematic review

BackgroundNeutropenic patients developing acute disseminated candidiasis may present with skin lesions.AimsTo evaluate the epidemiology of acute disseminated candidiasis with skin lesions in neutropenic patients, taking into consideration changes caused by different prophylactic strategies.SourcesA systematic review of English-language articles found via PubMed (1963–2016) was performed. We asked the following questions: (a) What Candida species are more frequently involved in this syndrome? (b) Has antifungal prophylaxis changed the species causing skin lesions? (c) What are the typical patterns of skin lesions? (d) What is the frequency of skin lesions in neutropenic patients with candidaemia or acute disseminated candidiasis? (e) Has antifungal prophylaxis decreased the incidence of acute disseminated candidiasis with skin lesions?ContentAmong 183 studies, 33 were selected, reporting 100 cases of acute disseminated candidiasis with skin lesions in neutropenic patients. It occurred more frequently in the setting of induction therapy for de novo or relapsed acute leukaemia, and the most frequent Candida species were C. tropicalis (68%) and C. krusei (15%). Diffuse maculopapular lesions predominated in cases caused by C. tropicalis and nodular and papular lesions in cases caused by C. krusei. Prophylaxis with fluconazole was reported in six cases, C. krusei in five and C. ciferrii in one. The death rate was 45.4%.ImplicationsTwo patterns were recognized: disseminated maculopapular lesions caused by C. tropicalis in patients not receiving fluconazole prophylaxis, occurring in 39% to 44% of neutropenic patients with acute disseminated candidiasis, and nodular lesions caused by C. krusei in patients receiving fluconazole prophylaxis, occurring less frequently.     

Hospital-related outbreaks due to rare fungal pathogens: a review of the literature from 1990 to June 2011

Fungi can cause severe infections. Two or more nosocomial unusual fungal infections diagnosed in a short period should be assumed as an outbreak. The review’s aim was to collect data to improve their management. The free online worldwide database for nosocomial outbreaks (http://www.outbreak-database.com) and the PubMed/MEDLINE database were used to collect the English literature published from 1990 to June 2011. The more common Candida spp. and Aspergillus spp. infections were excluded. For each outbreak, the following data were reviewed: species, duration, source and site of infection, ward, risk factors, number of patients infected, treatment, related mortality, type of epidemiological study and time elapsed between index cases and second cases. Thirty-six reports were considered: yeasts caused the majority of the outbreaks (16 out of 36). The median values for the overall duration, number of infected people per outbreak and infection-related mortality were 5?months, 4 and 20?%, respectively. Eighteen cases were caused by contaminated substances and 13 cases were hypothesised as human-transmitted. Nosocomial outbreaks due to rare fungal pathogens involve few patients but have high related mortality. These results could be explained by the diagnostic delay, the inability of recognising the source of the infections and the challenges of the treatment. More efforts should be concentrated to implement the application of proper hygiene practices to avoid human–human transmission.     

Time-trends for Gram-negative and multidrug-resistant Gram-positive bacteria associated with nosocomial infections in German intensive care units between 2000 and 2005.

This study analysed the time-trends for bacteria associated with nosocomial lower respiratory tract infections (LRTIs), bloodstream infections (BSIs) and urinary tract infections (UTIs) that were reported to the German Nosocomial Infection Surveillance System for intensive care units (ICUs). Data concerning 19 822 nosocomial infections were submitted by 139 ICUs between 2000 and 2005. There was a significant increase in the proportion of Gram-negative bacteria causing LRTIs (from 63.9% to 68.4%) and UTIs (from 65.3% to 68.6%). The proportion of BSIs caused by Gram-negative bacteria declined significantly, from 36.4% to 22.7%. The frequency of methicillin-resistant Staphylococcus aureus among all S. aureus isolates increased from 19.8% to 37.2%.     

Microbiologic aspects in patients with leukemia

Fever usually heralds the onset of infection in patients with leukemia. Neutropenia, inadequate synthesis of normal immunoglobulins, and chemotherapeutic agents all play a role in increasing the susceptibility of leukemic patients to infection. Most episodes of septicemia are caused by gram negative bacilli, especially E. coli, Klebsiella sp., and Pseudomonas aeruginosa. common organisms may cause uncommon types of infection in leukemic patients, and some infections are caused by organisms ordinarily considered to be nonpathogenic. It is advisable to obtain appropriate cultures regularly as long as fever persists.Several relatively new laboratory tests may allow more rapid detection of infection than is possible with routine microbiologic techniques. Serologic techniques show promise of aiding in the diagnosis of systemic fungal infections, especially of candidiasis. Recent attempts to prevent infections in highly susceptible leukemic patients have employed laminar air flow rooms to isolate the patient from nosocomial organisms, and oral doses of nonabsorbable antibiotics have been used along with topical administration of antibiotics in order to suppress the endogenous microbial flora. Studies to date have shown that the use of these prophylactic techniques can reduce the frequency of infections and help to prolong remissions in leukemic patients.     

Emergence in Brazil of methicillin-resistant Staphylococcus aureus isolates carrying SCCmecIV that are related genetically to the USA800 clone

An increasing incidence of nosocomial infections caused by non-multiresistant methicillin-resistant Staphylococcus aureus (nMMRSA) has been reported worldwide. The present study genotyped nMMRSA isolates obtained from hospitals in two cities in Brazil. The hospital isolates displayed pulsed-field gel electrophoresis (PFGE) patterns that were similar to those of the USA100 (ST5-SCCmecII) and USA 800 (ST5-SCCmecIV) strains, which are related to the New York/Japan and paediatric clones, respectively. Carriage of SCCmecIV and the classification by multilocus sequence typing (MLST) of a representative of this PFGE pattern in clonal complex 5 (CC5) confirmed the genetic relationship of the Brazilian isolates with USA800. The USA800-related Brazilian isolates were responsible for severe nosocomial infections in compromised adults and elderly patients in Brazil. A higher growth rate, an ability to form biofilm on inert polystyrene surfaces and the presence of the egc locus may have contributed, at least in part, to the fitness of these organisms as global nosocomial pathogens.     

Epidemiology of nosocomial fungal infections.

This paper briefly reviews the current knowledge of the epidemiology and modes of transmission of nosocomial fungal infections and some of the therapeutic options for treating these diseases. In the mid-1980s, many institutions reported that fungi were common pathogens in nosocomial infections. Most, if not all, hospitals care for patients at risk for nosocomial fungal infections. The proportion in all nosocomial infections reportedly caused by Candida spp. increased from 2% in 1980 to 5% in 1986 to 1989. Numerous studies have identified common risk factors for acquiring these infections, most of which are very common among hospitalized patients; some factors act primarily by inducing immunosuppression (e.g., corticosteroids, chemotherapy, malnutrition, malignancy, and neutropenia), while others primarily provide a route of infection (e.g., extensive burns, indwelling catheter), and some act in combination. Non-albicans Candida spp., including fluconazole-resistant C. krusei and Torulopsis (C.) glabrata, have become more common pathogens. Newer molecular typing techniques can assist in the determination of a common source of infection caused by several fungal pathogens. Continued epidemiologic and laboratory research is needed to better characterize these pathogens and allow for improved diagnostic and therapeutic strategies.     

Role of iron, capsule, and toxins in the pathogenicity of Vibrio vulnificus biotype 2 for mice.

The virulence mechanisms of Vibrio vulnificus biotype 2 have been studied and compared with those of biotype 1 in mice as the experimental animals. Biotype 2 isolates from European eels were as virulent for mice as biotype 1 strains (50% lethal dose, about 10(5) CFU per mouse); a septicemic infection developed in less than 24 h. These strains had several properties in common with biotype 1 organisms including capsule expression, uptake of various iron sources, and production of exoproteins, whose role in mouse virulence has been demonstrated. We also discuss the implication of biotype 2 strains in human infections.     

Typing of urogenital, maternal, and neonatal isolates of Haemophilus influenzae and Haemophilus parainfluenzae in correlation with clinical source of isolation and evidence for a genital specificity of H. influenzae biotype IV.

Over a period of 6 years, 114 strains of Haemophilus influenzae and Haemophilus parainfluenzae were isolated from genital, mother-infant, or neonatal infections. Their serotypes, biotypes, antibiotic resistance phenotypes, and outer membrane protein (OMP) electrophoretic patterns were characterized and correlated with the various clinical outcomes. Genital H. influenzae and H. parainfluenzae appeared to behave mostly as opportunistic pathogens; for instance, 62% of the cases of endometritis or pelvic inflammatory disease were related to the presence of an intrauterine device. However, as seen clearly in one case, the strains may be sexually transmitted. The analysis of OMP patterns proved to be a very convenient method to seek evidence for the sexual origin of the infection. H. influenzae was more often involved in complicated genital infections than was H. parainfluenzae. Nontypeable and biotype II H. influenzae strains were the more frequent isolates, except in pelvic inflammatory diseases, in which biotype I prevailed, and in mother-infant infections, in which one-fourth of the cases were due to biotype IV. Characterization of H. influenzae isolates did not support a general concept of specific genital strains. However, strains of biotype IV clearly stood out with two characteristics: (i) a peritrichous fimbriation and (ii) a very peculiar homogeneous OMP pattern comprising an OMP of molecular weight approximately 18,000 unique to this biotype. These characteristics were also found in H. influenzae biotype IV strains isolated from genital infections in the United States and used as controls. H. influenzae biotype IV strains may thus correspond to a group somewhat adapted to the genital tract.     

Nosocomial fungemia due to Exophiala jeanselmei var. jeanselmei and a Rhinocladiella species: newly described causes of bloodstream infection

Fungi have become increasingly important causes of nosocomial bloodstream infections. The major cause of nosocomial fungemia has been Candida spp, but increasingly molds and other yeasts have caused disease. Exophiala jeanselmei and members of the genus Rhinocladiella are dematiaceous moulds, which have been infrequently associated with systemic infection and have not been described as causes of fungemia. In this paper, the occurrence of 23 cases of fungemia due to these organisms over a 10-month period is reported and the clinical characteristics of patients and outcomes are described. The majority of patients were immunosuppressed; 21 of 23 (91%) had received blood products and 78% had a central venous catheter. All patients had at least one manifestation of fever, but only one patient had signs or symptoms suggesting deep-seated infection. Antifungal therapy was given to 19 of the 23 patients; of those who did not receive therapy, 3 died prior to the culture result and 1 had been discharged without therapy. Antifungal susceptibility of the organisms showed activity of amphotericin B, itraconazole, and the new triazole antifungals voriconazole and posaconazole. E. jeanselmei and Rhinocladiella species are potential causes of nosocomial fungemia and may be associated with systemic infection.     

Systemic fungal infections in neonates

Advances in neonatal management have led to considerable improvement in newborn survival. However, early (<72 hours) and late (>72 hours) onset systemic infections, both bacterial and fungal, remain a devastating complication and an important cause of morbidity and mortality in these babies. Most neonatal fungal infections are due to Candida species, particularly Candida albicans. The sources of candidiasis in NICU are often endogenous following colonization of the babies with fungi. About 10% of these babies get colonized in first week of life and up to 64% babies get colonized by 4 weeks of hospital stay. Disseminated candidiasis presents like bacterial sepsis and can involve multiple organs such as the kidneys, brain, eye, liver, spleen, bone, joints, meninges and heart. Confirming the diagnosis by laboratory tests is difficult and a high index of suspicion is required. The diagnosis of fungemia can be made definitely only by recovering the organism from blood or other sterile bodily fluid. Amphotericin B continues to be the mainstay of therapy for systemic fungal infections but its use is limited by the risks of nephrotoxicity and hypokalemia. Newer formulations of amphotericin B, namely the liposomal and the lipid complex forms, have recently become available and have been reported to have lesser toxicity. More recently Indian liposomal Amphotericin B derived from neutral lipids (L-Amp-LRC-1) has shown good response with less toxicity. A clinical trial with this preparation has shown to be safe and efficacious in neonatal fungal infections. Compared to other liposomal preparations, L-Amp-LRC-1 is effective at lower dose and is less expensive drug for the treatment of neonatal candidiasis.     

Clinical impact and pathogenicity of Acinetobacter

Members of the genus Acinetobacter have been implicated in a wide spectrum of infectious diseases. Although this organism is associated primarily with nosocomial infections, it has also been involved in cases of community-acquired infection. Before the 1970s, Acinetobacter infections were mostly post-surgical urinary tract infections in patients hospitalised in surgical units. The significant improvement in resuscitation techniques during the last 30 years has changed the types of infection caused by Acinetobacter. Since the 1980s, Acinetobacter has spread rapidly among patients in intensive care units. Today, Acinetobacter accounts for c. 9% of nosocomial infections, with most Acinetobacter infections involving the respiratory tract. Transmission via the hands of hospital staff has become the most important contributory factor in patient colonisation. Acinetobacter baumannii is the species that is involved most frequently in infections of humans, but a natural reservoir for A. baumannii outside the hospital environment has not yet been identified. Community-acquired infection and infections acquired following war or natural disasters (e.g., earthquakes) have been described. Acinetobacter causes mild-to-severe illness, but can be fatal. The severity of Acinetobacter infection depends upon the site of infection and the patient's susceptibility to infection as a result of underlying disease. The circumstances that allow Acinetobacter to assume a pathogenic role are not really well-understood. As this organism is a low-grade pathogen, the pathogenesis of Acinetobacter infections probably involves numerous factors, including virulence determinants, which have yet to be investigated.     

Outbreak of methicillin-resistant Staphylococcus aureus in general hospital intensive care unit]

Mantes' hospital polyvalent intensive care unit (ICU) experienced an outbreak episode caused by methicillin resistant Staphylococcus aureus (MRSA). Suspicion of physicians was strengthened by observing the weekly reading of multiresistant germs and the significative increase of MRSA carriers incidence rate, compared with the number of admission in the ICU: 5.5% to 11.3%. This outbreak was surprising: it happened immediately after the installation in a new hospital and the reinforcement of nosocomial infection surveillance (systematic screening of every patient admitted to the I.U.C., his isolation if he presents risk factors to multiresistant germs, increasing of handwashing stations). The overlapping period of hospitalisation concerning the 13 patients being reported as SARM carrier, having the same antibiogram, and the epidemic curve suggested a cross contamination. The index case was a MRSA carrier the day of her admission and have had a recent hospitalisation in a high risk unit. MRSA has always been isolated in nasal swab. Six patients among the thirteen carriers developed an infection and have been treated by vancomycin: two systemic infections and four pulmonary infections. The mortality rate was 33% and only one of them seemed to be directly due to MRSA. Area samples were all negative. The clinical staff have been screened with nasal swab. We identified only one nasal MRSA carrier. The pulsed-field gel electrophoresis study showed that 9/11 which have been analysed were identical. This outbreak brought about staff, more sensibilisation to the nosocomial infection and updating of plain hygien rules leaded to its stop five months later.     

Hospital-acquired rotavirus acute gastroenteritis in 10 consecutive seasons in Umbria (Italy)

Group A rotaviruses (RVA) are the leading cause of acute gastroenteritis (AGE) in young (aged <5 years) children. Several studies showed that RVA is one of the main cause of nosocomial gastroenteritis in hospitalized pediatric population worldwide, with an incidence ranging from 8 to 33 cases per 100 hospitalized children. Nosocomial infections, in which AGE symptoms develop at least 2 days after admission, may severely affect children already admitted to hospital for other causes. This study aimed to define the trends of the RVA genotypes through statistical analysis of the data obtained by the rotavirus surveillance in Umbria in 10 consecutive seasons, from 2007-2008 to 2016-2017, with update information on hospital-acquired RVA AGE. During RVA gastroenteritis surveillance in Umbria (Italy) in 2007 to 2017, a total of 741 RVA positive faecal samples were collected from children hospitalized with AGE, and RVA strains were genotyped following standard EuroRotaNet protocols. Of the 741 analyzed samples, 75 (10%) were reported to be hospital-acquired. Comparing the distributions of the RVA genotypes circulating in the community or associated with nosocomial infections, we observed a different distribution of genotypes circulating inside the hospital wards, with respect to those observed in the community except in 2010 to 2011, 2011 to 2012, and 2012 to 2013 when G1P[8], G4P[8] and the novel strain G12P[8] caused a large community- and hospital-acquired outbreak. Of the 741 analyzed samples, 75 (10%) were reported to be hospital-acquired. Comparing the distributions of the RVA genotypes circulating in the community or associated with nosocomial infections, we observed a different distribution of genotypes circulating inside the hospital wards, with respect to those observed in the community except in 2010 to 2011, 2011 to 2012, and 2012 to 2013 when G1P[8], G4P[8], and the novel strain G12P[8] caused a large community- and hospital-acquired outbreak. The information from this study will be useful to implement guidelines for preventing nosocomial RVA AGE, which should include an improved management of the hospitalized patients and an increase in vaccination coverage.     

Cervical osteomyelitis caused by Pseudomonas cepacia in an intravenous-drug abuser.

We report a case of vertebral osteomyelitis caused by Pseudomonas cepacia in a patient with a history of intravenous-drug abuse. P. cepacia infections are usually nosocomial, although community-acquired infections occur more commonly in intravenous-drug abusers than in the general population. Vertebral osteomyelitis caused by P. cepacia has not previously been reported.