Sigmund Krajden

Complicated and fatal Strongyloides infection in Canadians: risk factors, diagnosis and management

STRONGYLOIDIASIS, WHICH IS CAUSED by the nematode Strongyloides stercoralis, is a common and persistent infection, particularly in developing countries. In the setting of compromised cellular immunity, it can result in fulminant dissemination with case-fatality rates of over 70%. The majority of new Canadian immigrants come from countries where Strongyloides is highly endemic; therefore, the burden of Strongyloides may be underappreciated in Canada. Because early diagnosis and therapy can have a marked impact on disease outcome, screening for this infection should be considered mandatory for patients who have a history of travel or residence in a disease-endemic area and risk factors for disseminated disease (e.g., corticosteroid use and human T-lymphotropic virus type I infection).

Potted plants in hospitals as reservoirs of pathogenic fungi

The soils of five potted plants cultivated within a hospital were investigated for the presence of fungal opportunistic pathogens of humans. A total of 16 potentially pathogenic species were isolated, including Aspergillus fumigatus at up to 53.5 colony-forming units (CFU) per gram dry soil and Scedosporium apiospermum (Pseudallescheria boydii) at up to 97.0 CFU/g. Other common species included Phialophora verrucosa and Fusarium solani. Scedosporium inflatum, a recently described emerging pathogen, is reported for the first time from an environmental source. The results of this study, in combination with previous case reports linking mycoses to potted plants and available information on the establishment and dispersal of fungal opportunistic pathogens in indoor habitats, indicate that indoor plant soils constitute a serious mycotic hazard to the immunosuppressed patient.

Subcutaneous phaeohyphomycosis caused by Lasiodiplodia theobromae and successfully treated surgically

While visiting Jamaica, a 50-year-old woman stumbled on an outdoor wooden staircase and sustained an injury to the right leg. The wound was cleaned topically and the patient was given antibacterial therapy. Five weeks later, in Canada, she presented with an ulcer at the injury site. An excisional biopsy showed copious broad, septate, melanized fungal filaments penetrating into tissue. Culture yielded a nonsporulating melanized mycelium. The isolate was strongly inhibited by cycloheximide and benomyl but grew at 37 degrees C. After 16 weeks cultivation on modified Leonians agar at 25 degrees C, it developed pycnidia characteristic of Lasiodiplodia theobromae, a common tropical phytopathogen mainly known previously as a rare agent of keratitis and onychomycosis in humans. The patient was not given antifungal chemotherapy, and the ulcer, which had been broadly excised in the biopsy procedure, ultimately resolved after treatment with saline compresses. The six-month follow-up showed no sign of infection. This case, interpreted in light of previously reported cases, shows that on rare occasions L. theobromae is able to act as an agent of subcutaneous phaeohyphomycosis and that, when this occurs, debridement alone may be sufficient to eradicate it.

Pneumococcal vaccination programs and the burden of invasive pneumococcal disease in Ontario, Canada, 1995–2011

BACKGROUND In 1995, a publicly funded pneumococcal vaccination program for 23-valent polysaccharide vaccine (PPV23) was introduced in Ontario. Conjugate vaccines were authorized in 2001 (PCV7), 2009 (PCV10) and 2010 (PCV13). METHODS From 1995-2011, active, population-based surveillance for invasive pneumococcal disease (IPD) was conducted in Metropolitan Toronto and Peel Region, Canada. RESULTS 6404 IPD cases were included. After PPV23 program implementation in 1995, IPD due to PPV23 strains decreased 49% in older adults prior to PCV7 introduction. Estimated PPV23 efficacy in vaccine eligible adults was 42.2% (95% CI; 28.6-53.2%). IPD incidence due to PCV7 serotypes in children <5 years decreased significantly after PCV7 authorization and before introduction of a publicly funded PCV7 program. Seven years after PCV7 program implementation, the incidence of IPD due to PCV7 serotypes decreased to zero in children and by 88% in adults, however, overall IPD incidence remained unchanged in adults. In 2011, the incidence of IPD was 4.5 per 100,000 in adults aged 15-64 and 19.9 per 100,000 in adults aged over 65 years, with 45 serotypes causing disease. Between 1995 and 2011, the case fatality rate of IPD in adults decreased 2% per year (95% CI, -0.9% to -3.2%). In multivariable analysis, predictors of mortality included older age, chronic conditions, nursing home residence, current smoking, bacteraemia, and illness due to serotypes 3,11A, 19A, and 19F. CONCLUSIONS While vaccination programs resulted in substantial public health benefits, herd immunity benefits of PCV7 were seen at low pediatric vaccination rates, and the case fatality rate of IPD has decreased, IPD will continue to be a cause of considerable morbidity and mortality in adults.

Invasive Pneumococcal Disease Among Immunocompromised Persons: Implications for Vaccination Programs

BACKGROUND In 2012/2013, a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) was recommended for immunocompromised adults in the United States and Canada. To assess the potential benefits of this recommendation, we assessed the serotype-specific burden of invasive pneumococcal disease (IPD) among immunocompromised individuals. METHODS From 1995 to 2012, population-based surveillance for IPD was conducted in Metropolitan Toronto and Peel Region, Canada. Disease incidence and case fatality were measured in immunocompromised populations over time, and the contribution of different serotypes determined. RESULTS Overall, 2115/7604 (28%) episodes of IPD occurred in immunocompromised persons. IPD incidence was 12-fold higher (95% confidence interval [CI], 8.7-15) in immunocompromised compared to immunocompetent persons; the case fatality rate was elevated in both younger (odds ratio [OR] 1.8) and older (OR 1.3) adults. Use of immunosuppressive medications was associated with a 2.1-2.7 fold increase in the risk of IPD. Five years after PPV23 program implementation, IPD incidence had declined significantly in immunocompromised adults (IRR 0.57, 95% CI, .40-.82). Ten years after pediatric PCV7 authorization, IPD due to PCV7 serotypes had decreased by 90% (95% CI, 77%-96%) in immunocompromised persons of all ages. In 2011/2012, 37% of isolates causing IPD in immunocompromised persons were PCV13 serotypes and 27% were PPV23/not PCV13 serotypes. CONCLUSIONS Immunocompromised individuals comprised 28% of IPD. Both PPV23 and herd immunity from pediatric PCV7 were associated with reductions in IPD in immunocompromised populations. PCV13 vaccination of immunocompromised adults may substantially reduce the residual burden until herd immunity from pediatric PCV13 is fully established.

Surveillance for hospital outbreaks of invasive group a streptococcal infections in Ontario, Canada, 1992 to 2000.

Context Hospital outbreaks of invasive group A streptococcal infection are a potentially preventable source of morbidity and mortality. Contribution In Ontario, Canada, 291 cases of hospital-acquired invasive group A infection occurred between 1992 and 2000; 10% of these infections occurred during 20 outbreaks in the hospital. Although nosocomial infections were most common in surgical and obstetric patients, most outbreaks of streptococcus A infection occurred outside of those settings. One quarter of the outbreaks was related to community-acquired infections (mostly necrotizing fasciitis) requiring intensive care; the bacteria were primarily transmitted from patient to patient. Implication Isolation of patients with necrotizing fasciitis may be an important strategy to reduce hospital outbreaks of invasive group A streptococcal infection. The Editors Streptococcus pyogenes has the capacity to produce myriad invasive diseases, the most dramatic being necrotizing fasciitis and streptococcal toxic shock syndrome (1). The rate of invasive disease has increased in recent decades to more than 3 per 100000 persons per year, and the case-fatality rate remains approximately 15% (2, 3). Equally as dramatic as the illness that group A streptococcus produces in individual patients are the outbreaks it has caused in hospitals (463). Such outbreaks have involved as many as 56 patients and health care workers and have continued for as long as 3 years (32, 39). Preventing hospital transmission of group A streptococcal infection would allow for the prevention of many secondary cases of disease (64). The current Centers for Disease Control and Prevention (CDC) recommendations for preventing nosocomial outbreaks exist only for postpartum and postsurgical settings and are based on expert opinion and a review of a limited number of outbreaks (6, 28, 32, 41, 55, 58, 65). This study sought to describe the epidemiology of hospital outbreaks of invasive group A streptococcal disease in Ontario, Canada, in order to assess the utility of proposed strategies for the prevention, investigation, and management of clusters of this disease (66). Methods Surveillance Prospective, population-based surveillance of all invasive group A streptococcal infections was conducted in the province of Ontario, Canada, from 1 January 1992 to 31 December 2000, as described elsewhere (2, 3). All Ontario microbiology laboratories processing sterile-site specimens telephoned the central study office whenever group A streptococcus was identified from a specimen from any sterile site. Annual audits were performed in all laboratories to ensure complete case ascertainment. Case definitions are described elsewhere (3). Invasive group A streptococcal infection was defined as illness associated with isolation of group A streptococcus from a normally sterile body site. Infections were deemed hospital acquired if disease was neither present nor incubating at the time of admission (67). The Ontario Group A Streptococcal surveillance system was approved by the institutional review boards of the University of Toronto and participating hospitals. Investigation of Disease Transmission When a nosocomial case of group A streptococcus was identified, study staff contacted the hospitals infection control practitioner to offer recommendations regarding investigation. Recommendations included 1) case finding in hospital patients, staff, and family members; 2) screening close contacts of the patient for symptoms of group A streptococcal infection; 3) taking additional precautions or restricting work for acutely ill contacts; 4) obtaining throat swabs and considering vaginal and rectal swabs from contacts for group A streptococcal culture; and 5) typing any isolates obtained. An outbreak was defined as the occurrence of at least 2 cases of culture-confirmed, symptomatic infection that were epidemiologically linked and were caused by isolates of the same M and T type and were indistinguishable by pulsed-field gel electrophoresis (3). Study staff were available for consultation during these investigations, and typing of isolates was provided by the study. Laboratory Methods Clinical isolates were identified as S. pyogenes using standard methods. Both M serotyping and T agglutination typing were performed at the Canadian National Centre for Streptococcus, Edmonton, Alberta, Canada (6870). Pulsed-field gel electrophoresis was performed as described elsewhere (71). Statistical Analysis Surveillance data were entered in duplicate and were analyzed in SAS for Windows, version 8 (SAS Institute, Cary, North Carolina). Differences in proportions were assessed by using Fisher exact tests, and differences in continuous variables were evaluated by using Wilcoxon rank-sum tests. Role of the Funding Sources Surveillance was funded by the CDC and by the Department of Microbiology at the Mount Sinai Hospital. These funding sources contributed to the design of surveillance but had no influence on the conduct or reporting of this study or the decision to submit the manuscript for publication. Results In prospective surveillance from 1 January 1992 to 31 December 2000, 2351 cases of invasive group A streptococcal disease were detected in Ontario (3) (Table 1). Of the 291 nosocomial invasive group A streptococcal infections, 29 (10%) were associated with 20 outbreaks. These 20 nosocomial outbreaks also involved 26 laboratory-confirmed noninvasive group A streptococcal illnesses, for a total of 53 outbreak-associated patient cases (there were 6 cases in health care workers, all pharyngitis). The average rate of outbreaks over the 9-year period was 1.0 per 100 hospitals per year, with an average rate of outbreak-associated disease of 0.5 per 100000 hospital admissions per year. Table 1. Characteristics of Invasive Group A Streptococcal Disease Cases in Ontario, 19922000 The clinical presentations of the 29 invasive cases associated with outbreaks did not differ from those of all invasive disease cases (data not shown). The case-fatality rate of outbreak-associated invasive cases (24% [7 of 29]) did not statistically significantly differ from that of all cases of invasive infection (16% [347 of 2242]; P= 0.20) or that of sporadic nosocomial infections (17% [42 of 255]; P> 0.2). Table 2 details the characteristics of the 20 nosocomial outbreaks. The outbreaks were distributed evenly over time and occurred in 15 institutions. Five (25%) outbreaks included at least 1 surgical site infection; 6 (30%) included at least 1 postpartum infection; and 14 (70%) included at least 1 nonsurgical, nonobstetric infection. Five (25%) outbreaks involved a mix of 2 or more case types. Nonsurgical, nonobstetric infections encompassed a broad range of syndromes, including primary bacteremia (5 cases), soft-tissue infection (5 cases), pneumonia (4 cases), pharyngitis (2 cases), and peritonitis (1 case). Table 2. Nosocomial Outbreaks of Group A Streptococcal Infection Identified via Prospective Surveillance in Ontario, 19922000 In 5 (25%) outbreaks, transmission was initiated by admission of a patient with community-acquired invasive group A streptococcal infection. All community-acquired index cases involved necrotizing fasciitis or a draining soft-tissue infection, and 4 of the 5 patients were admitted directly to an intensive care unit. Outbreak initiation and propagation were rapid, with a median interval between first and second cases of 4.5 days (range, 0 to 30 days) and a median interval between any 2 subsequent cases of 2 days (range, 0 to 11 days). Fourteen outbreaks (70%) involved only 2 cases. The largest outbreak involved 10 cases: 6 health care workers and 4 patients. Only 2 (10%) outbreaks lasted more than 2 weeks, and none lasted more than 1 month. The most common mode of outbreak propagation was patient-to-patient transmission (via a person or the environment), judged as primarily responsible for 12 (60%) outbreaks. Transmission from a staff carrier was the sole source of transmission in 1 (5%) outbreak, mixed patient-to-patient transmission and staff transmission contributed to 1 (5%) outbreak, and in 1 (5%) outbreak it could not be determined whether transmission occurred from a staff carrier or by patient-to-patient spread. The mode of propagation could not be ascertained in the remaining 5 (25%) outbreaks. Transmission via the inanimate environment was suspected in 2 situations. One patient developed group A streptococcal pneumonia 2 days after being admitted to the intensive care unit room and bed of a patient who had died of necrotizing fasciitis. No staff had contact with both patients. Another patient developed a postoperative surgical site infection 24 hours after having a biopsy in an operating room in which the previous procedure (completed 6 hours before) was debridement of necrotizing fasciitis. Again, no staff had contact with both patients. In 3 of the 11 (26%) remaining outbreaks thought to be propagated from patient to patient, roommates of index patients developed acute infection. The staff carrier implicated as a sole source was a colonized surgeon linked to 3 surgical site infections over a 10-day period. One colonized obstetrician was probably responsible for propagation of 2 of 3 secondary cases of postpartum disease in another outbreak, and 1 colonized nurse may have been responsible for propagation to 2 patients on a medical ward in a third outbreak. In 5 of 10 (46%) other investigated outbreaks, at least 1 colonized or infected staff person was identified; in all cases, a health care worker may have transmitted S. pyogenes to 1, but not more than 1, of the outbreak-associated cases. Although a staff carrier was the primary mode of transmission in only 2 (10%) outbreaks, 1 or more health care workers were colonized with the outbreak strain in 6 of 18 (33%) other outbreaks. In 5 outbreaks (25%), health care workers who were screened were colonized with nonoutbreak strains. In outbreaks

An Outbreak of Staphylococcus Epidermidis Septicemia

During 45 wk from August 1980 to June 1981, the catheter sepsis rate increased from a prior 2 to 34% (23 of 68 patients on intravenous hyperalimentation). The causative organism was Staphylococcus epidermidis, grown on blood cultures in 21 of the 23 patients and on the catheter-tips of all 23. Routine cultures of the catheter-tips of the 45 patients who received intravenous hyperalimentation during this period with no evidence of catheter sepsis grew S. epidermidis on three catheter-tips (6.7%), possibly contamination during catheter removal. Sepsis resolved within 24 hr after catheter removal, with no antibiotics given for the sepsis. The organism had identical antibiograms on the blood and catheter-tip cultures in each patient, but antibiograms varied between patients. In these complex patients undergoing multiple medical events, the intravenous hyperalimentation nurse recorded that iv tubing in septic patients had leaked solution at the attachment to the catheter hub, and a review of nursing notes on charts of patients who had been on intravenous hyperalimentation revealed that a leak had been noted in the patients who subsequently had catheter sepsis. The leak was due to a manufacturing defect resulting in a decrease in diameter of the plastic connection of the iv tubing, which produced a loose attachment to the hub. The problem was remedied by switching to a Luer-lok attachment. However, in July 1982, two patients had separation of the Luer due to a manufacturing defect in the threads, followed by a catheter sepsis. Sepsis from the local contamination was not manifest until 5.4 +/- 2.7 days later. Quality control by manufacturers is emphasized.

Klebsiella pneumoniae Carbapenemase, Canada

To the Editor: Carbapenems are used to treat life-threatening infections caused by extremely drug-resistant gram-negative pathogens; these drugs represent the last line of defense in the antimicrobial drug armamentarium against serious or invasive infection (1). The rapid global spread of Klebsiella pneumoniae that produces K. pneumoniae carbapenemase (KPC), especially in the northeastern United States (e.g., New York state), is of major concern (2,3). KPC β-lactamases belong to the family of serine carbapenemases and are usually found in K. pneumoniae and Escherichia coli. KPC hydrolyzes β-lactam agents, thereby reducing their action. KPC activity has been reported, albeit less frequently, in other family Enterobacteriaceae (K. oxytoca, Enterobacter spp., Salmonella spp., Citrobacter freundii, and Serratia spp.) as well as in Pseudomonas aeruginosa (1). The blaKPC genes have been identified on conjugative plasmids and pose an infection control problem because plasmids could theoretically be transmitted from one species to another (4). The few therapeutic options for treating infections caused by organisms containing these β-lactamases are aminoglycosides, glycylcyclines, polymyxins, or combinations (1). A major concern is that routine susceptibility testing methods based on existing breakpoints can falsely identify KPC producers as susceptible to carbapenems. Such results pose the potential risk for increased illness and death, longer hospital stays, and nosocomial spread of infection. In 2008, the Public Health Laboratory in Toronto received clinical isolates of K. pneumoniae from urine and sputum of 1 patient. The hospital laboratory had forwarded the isolates to the Public Health Laboratory because they were possible KPC producers. The patient was a 73-year-old man with a history of emphysema and hypertension, seen at a tertiary care hospital in the Toronto area, 80 miles from the New York state border, for a laparoscopic right radical nephrectomy because of hypernephroma. He had no risk factors for acquisition of KPC producers, e.g., travel to the United States or prior carbapenem exposure. Susceptibility testing of K. pneumoniae was performed by the agar dilution method, using breakpoints set by the Clinical and Laboratory Standards Institute (5,6). The sputum isolate (7315) was susceptible to meropenem (MIC 4 μg/mL), and the urine isolate (7184) was intermediately susceptible (MIC 8 μg/mL). The K. pneumoniae isolates were screened for extended-spectrum β-lactamases (ESBLs) and AmpC production according to Ontario guidelines (7). Briefly, to screen for ESBL enzymatic activity, a double-disk diffusion method was used: a clavulanic acid–containing disk was placed adjacent to a disk containing one of several cephalosporins such as ceftazidime and cefotaxime. Enhanced killing of the organism in the area between the drug with and without clavulanate indicates ESBL. Cefoxitin resistance (zone <17 mm) indicates AmpC-like β-lactamase activity. In addition, testing for ESBL/AmpC was performed according to Clinical and Laboratory Standards Institute guidelines (6). When the screening result for ESBL or AmpC is positive, the clinical laboratory issues a warning that no β-lactam except carbapenems can effectively treat this infection. The Table summarizes results of initial susceptibility testing and supplementary laboratory testing for KPC. Table Results of initial susceptibility and supplementary testing for Klebsiella pneumoniae carbapenemase in urine and sputum samples from 73-year-old man, Canada* The initial result was consistent with a possible AmpC/ESBL producer for the sputum and urine isolates (6,7). However, because the patient responded poorly to empiric vancomycin and imipenem therapy and because of the elevated MIC to meropenem for isolate 7184, further laboratory testing was conducted to rule out the possibility of carbapenemase activity. The modified Hodge test is a phenotypic test proposed to confirm the presence of carbapenemase activity such as KPC in K. pneumoniae and E. coli (8). Universal primers for blaKPC family, Uni-KPC-F (5′-ATGTCACTGTATCGCCGTCT-3′) and -R (5′-TTACTGCCCGTTGACGCCC-3′), were used for the entire 882-bp coding sequence. Amplicons were bidirectionally sequenced by using the BigDye Terminators method and a 3130xl Genetic Analyzer (Applied Biosystems, Foster City, CA, USA) and primers Uni-KPC-F and -R. Multiple nucleotide and protein sequence alignments were performed with the ClustalW2 software (www.ebi.ac.uk/Tools/clustalw2/index.html). To aid the clinician, an Etest method was used to measure the MIC of this KPC-producing K. pneumoniae isolate to colistin (0.5 μg/mL) and tigecycline (2.0 μg/mL). However, before this information could be used, the patient had died of respiratory failure, presumably caused by K. pneumoniae. Infection control measures and laboratory screening were undertaken in the hospital to limit transmission to other patients. This report shows that KPC-producing organisms such as K. pneumoniae may pose a major risk for clinical disease and a challenge for infection control if they were to spread to other hospitals in Canada. Current testing algorithms focus on ESBL- and AmpC-producing gram-negative bacteria, which may not detect KPC-producer strains. We suggest that reference laboratories validate a screening method coupled with confirmatory phenotypic assay for carbapenemase activity for suspected organisms, especially K. pneumoniae and E. coli. Our in-house validation studies confirm that use of the ertapenem disk followed by the modified Hodge test to confirm carbapenemase activity may be effective (D.R. Pillai et al., unpub. data). Public health officials should be aware that this report further expands the international distribution of KPC-producing K. pneumoniae.

A Review of Amoebic Liver Abscess for Clinicians in a Nonendemic Setting

Amoebic liver abscess (ALA) is an uncommon but potentially life-threatening complication of infection with the protozoan parasite Entamoeba histolytica. E histolytica is widely distributed throughout the tropics and subtropics, causing up to 40 million infections annually. The parasite is transmitted via the fecal-oral route, and once it establishes itself in the colon, it has the propensity to invade the mucosa, leading to ulceration and colitis, and to disseminate to distant extraintestinal sites, the most common of which is the liver. The authors provide a topical review of ALA and summarize clinical data from a series of 29 patients with ALA presenting to seven hospitals in Toronto, Ontario, a nonendemic setting, over 30 years.

Attempted isolation of Blastomyces dermatitidis from native shrews in northern Wisconsin, USA

The precise ecological niche of Blastomyces dermatitidis is unknown. The related dimorphic fungus, Paracoccidioides brasiliensis, has been isolated from South American ground-dwelling insectivorous armadillos. We attempted to isolate Blastomyces from shrews, North American ground-dwelling insectivores that have been shown to harbor Histoplasma capsulatum in endemic areas. Forty-seven masked shrews (Sorex cinereus) and 13 northern short-tailed shrews (Blarina brevicauda) were collected in endemic areas of northern Wisconsin and Michigan using pitfall traps. Specimens were collected between 1998 and summer 2002, stored frozen, then necropsied. Cultures of nasopharynx, lungs, liver, spleen and large and small bowel were placed on yeast extract phosphate agar with one or two drops of ammonium hydroxide. Cultures for Blastomyces were negative from all 60 shrews and two deer mice (Peromyscus maniculatus) and three southern red-backed voles (Clethrionomys gapperi), which were trapped inadvertently. Histological examination of 36 of these specimens revealed no Blastomyces yeast forms. Northern Wisconsin shrews do not appear to be carriers of B. dermatitidis.