Fatal Respiratory Diphtheria Caused by ß-Lactam-Resistant Corynebacterium diphtheriae.

BACKGROUND: Diphtheria is a potentially fatal respiratory disease caused by toxigenic Corynebacterium diphtheriae. Although resistance to erythromycin has been recognized, ß-lactam resistance in toxigenic diphtheria has not been described. Here, we report a case of fatal respiratory diphtheria caused by toxigenic C. diphtheriae resistant to penicillin and all other ß-lactam antibiotics, and describe a novel mechanism of inducible carbapenem resistance associated with the acquisition of a mobile resistance element. METHODS: Long-read whole-genome sequencing was performed using Pacific Biosciences Single Molecule Real-Time sequencing to determine the genome sequence of C. diphtheriae BQ11 and the mechanism of ß-lactam resistance. To investigate the phenotypic inducibility of meropenem resistance, short-read sequencing was performed using an Illumina NextSeq500 sequencer on the strain both with and without exposure to meropenem. RESULTS: BQ11 demonstrated high-level resistance to penicillin (benzylpenicillin minimum inhibitory concentration [MIC] ≥ 256 µg/ml), ß-lactam/ß-lactamase inhibitors and cephalosporins (amoxicillin/clavulanic acid MIC ≥ 256 µg/mL; ceftriaxone MIC ≥ 8 µg/L). Genomic analysis of BQ11 identified acquisition of a novel transposon carrying the penicillin-binding protein (PBP) Pbp2c, responsible for resistance to penicillin and cephalosporins. When strain BQ11 was exposed to meropenem, selective pressure drove amplification of the transposon in a tandem array and led to a corresponding change from a low-level to a high-level meropenem-resistant phenotype. CONCLUSIONS: We have identified a novel mechanism of inducible antibiotic resistance whereby isolates that appear to be carbapenem susceptible on initial testing can develop in vivo resistance to carbapenems with repeated exposure. This phenomenon could have significant implications for the treatment of C. diphtheriae infection, and may lead to clinical failure.

Cryptococcal infections over a 15 year period at a tertiary facility & impact of guideline management.

Cryptococcosis is an invasive fungal infection caused primarily by Cryptococcus neoformans and Cryptococcus gattii species, presenting predominantly as meningoencephalitis. The aim of this study is to assess all cryptococcal infections managed at our facility from 2001 to 2015 to determine incidence, risk factors, and comparison of outcomes prior to and following introduction of the 2010 Infectious Disease Society of America (IDSA) guidelines. Retrospective analysis of all patients diagnosed and treated for cryptococcal infection occurring between January 2001 and December 2015. Of 102 patients diagnosed with cryptococcal infection, 97 were eligible for study inclusion. There appears to be an overall increased incidence of cryptococcosis in both transplant and non-transplant cohorts with a peak in 2015 of 6 transplant and 13 non-transplant cases. In the meningitis cohort, 38/52 (73%) of identified isolates were C. neoformans, and 14/52 (27%) were C. gattii. Notably, 14/14 (100%) of C. gattii isolates were associated with meningitis, as compared to only 38/64 (59%) C. neoformans associated with meningitis (P: .003). It appears that patients presenting with cough are less likely to have meningitis, 17/27 (63%), (P: .005). When stratifying for culture positive meningitis lumbar puncture opening pressure, the median in the culture positive cohort was 31.5 cm H2 O compared with 15.5 cm H2 O (P: .036).Multiple admissions were required prior to diagnosis in the majority of cases with only 18/72 (25%) diagnosed on 1st presentation. Postguideline mortality has improved from 15% to 6.1% (P: .046). Cryptococcal infection remains relatively uncommon, but there appears to be an increasing trend in incidence. Overall mortality is relatively low and has improved since introduction of the 2010 IDSA guidelines.

Cryptococcal infections in solid organ transplant recipients over a 15-year period at a state transplant center.

BACKGROUND: The aim of this research paper was to determine the incidence, risk factors, and clinical outcome of solid organ transplant (SOT) recipients diagnosed and treated for cryptococcosis at our institution. METHODS: Retrospective analysis of all patients with SOT diagnosed and treated for cryptococcal infection occurring between January 2001 and December 2015. RESULTS: Of 102 patients diagnosed with cryptococcal infection, 23 were SOT recipients. Renal transplant accounted for 22/23 cases, of which 13 had meningitis. The annual incidence of infection has risen significantly, and is now greater than 2/1000 prevalent renal transplant recipients. As expected, biochemical factors associated with meningitis include lower glucose on cerebrospinal fluid (CSF) analysis, median 2.4 vs 4.5 mmol/L (P=.02); CSF white blood cell median 50 vs 1/µL (P<.001); CSF protein, median 950 vs 335 mg/L (P=.04). Serum cryptococcal antigen titers were higher in the meningitis cohort, median 512 vs 32 (P=.03). Clinically, headache on admission (odds ratio: 9 [1.29-63.03], P=.03) and a prolonged length of stay (median of 36 vs 13 days) in the meningitis cohort (P=.02) were significant. CONCLUSION: Cryptococcal infection in SOT recipients remains rare; however, there has been a marked increase in cases since 2014. This study reveals a need for increased vigilance for a potential emerging infectious disease. It furthermore highlights the need for ongoing research to further aid early diagnosis, prognostication, management, and screening cost-effectiveness.

Characterising health care-associated bloodstream infections in public hospitals in Queensland, 2008-2012.

OBJECTIVE: To describe the epidemiology and rates of all health care-associated bloodstream infections (HA-BSIs) and of specific HA-BSI subsets in public hospitals in Queensland. DESIGN AND SETTING: Standardised HA-BSI surveillance data were collected in 23 Queensland public hospitals, 2008-2012. MAIN OUTCOME MEASURES: HA-BSIs were prospectively classified in terms of place of acquisition (inpatient, non-inpatient); focus of infection (intravascular catheter-associated, organ site focus, neutropenic sepsis, or unknown focus); and causative organisms. Inpatient HA-BSI rates (per 10,000 patient-days) were calculated. RESULTS: There were 8092 HA-BSIs and 9418 causative organisms reported. Inpatient HA-BSIs accounted for 79% of all cases. The focus of infection in 2792 cases (35%) was an organ site, intravascular catheters in 2755 (34%; including 2240 central line catheters), neutropenic sepsis in 1063 (13%), and unknown in 1482 (18%). Five per cent (117 of 2240) of central line-associated BSIs (CLABSIs) were attributable to intensive care units (ICUs). Eight groups of organisms provided 79% of causative agents: coagulase-negative staphylococci (18%), Staphylococcus aureus (15%), Escherichia coli (11%), Pseudomonas species (9%), Klebsiella pneumoniae/oxytoca (8%), Enterococcus species (7%), Enterobacter species (6%), and Candida species (5%). The overall inpatient HA-BSI rate was 6.0 per 10,000 patient-days. The rates for important BSI subsets included: intravascular catheter-associated BSIs, 1.9 per 10,000 patient-days; S. aureus BSIs, 1.0 per 10,000 patient-days; and methicillin-resistant S. aureus BSIs, 0.3 per 10,000 patient-days. CONCLUSIONS: The rate of HA-BSIs in Queensland public hospitals is lower than reported by similar studies elsewhere. About one-third of HA-BSIs are attributable to intravascular catheters, predominantly central venous lines, but the vast majority of CLABSIs are contracted outside ICUs. Different sources of HA-BSIs require different prevention strategies.

No evidence of prolonged Hendra virus shedding by 2 patients, Australia.

To better understand the natural history of Hendra virus infection and its tendency to relapse, 2 humans infected with this virus were monitored after acute infection. Virus was not detected in blood samples when patients were followed-up at 2 and 6 years. Thus, no evidence was found for prolonged virus shedding.

Human Hendra virus encephalitis associated with equine outbreak, Australia, 2008.

A recent Hendra virus outbreak at a veterinary clinic in Brisbane, Queensland, Australia, involved 5 equine and 2 human infections. In contrast to previous outbreaks, infected horses had predominantly encephalitic, rather than respiratory, signs. After an incubation period of 9-16 days, influenza-like illnesses developed in the 2 persons before progressing to encephalitis; 1 died. Both patients were given ribavirin. Basal serum and cerebrospinal fluid levels were 10-13 mg/L after intravenous administration and 6 mg/L after oral administration (isolate 90% inhibitory concentration 64 mg/L). Both patients were exposed to infected horses, 1 during the late incubation period in a horse. The attack rate for veterinary clinic staff exposed to infected horses was 10%. An isolate from this outbreak showed genetic heterogeneity with isolates from a concurrent, but geographically remote, outbreak and from previous outbreaks. Emergence of Hendra virus is a serious medical, veterinary, and public health challenge.

Arthroscopic treatment of septic arthritis of the hip.

Arthrotomy is considered standard treatment for septic arthritis of the hip; the procedure may be complicated by avascular necrosis or postoperative hip instability. Arthroscopic treatment of patients with this condition is still not an established technique, despite its minimally invasive nature and the fact that it is associated with low morbidity. A 3-portal arthroscopic technique by Byrd with the patient in the supine position was used for drainage, debridement, and irrigation in 6 patients with septic coxarthrosis. Continuous postoperative intra-articular irrigation was not provided, nor were postoperative decompression drains used. All patients were treated with intravenous antibiotics for 3 weeks, followed by oral antibiotics for an additional minimum of 3 weeks. Patients were followed for 6 to 42 months. Staphylococcus aureus was identified in 4 of the 6 patients. All patients had a rapid postoperative recovery. Mean Harris Hip Score at the last review was 97.5 points. All patients showed full range of motion of the affected hip. No complications occurred with this group of patients. Thus, 3-directional arthroscopic surgery combined with large-volume irrigation is an effective treatment modality in cases of septic arthritis of the hip. It is less invasive than arthrotomy and offers low rates of postsurgical morbidity.

Nontraumatic paecilomyces anterior segment infection: a pathognomonic clinical appearance.

PURPOSE: The aim of this study was to review a series of consecutive cases of corneal and scleral infection by Paecilomyces spp. and to identify features of clinical presentation and assess treatment modalities. METHODS: This retrospective review of a case series included 22 patients with nontraumatic Paecilomyces anterior segment infections who were seen in a tertiary referral practice. Outcome measures were the number of eyes that were lost and visual acuity in eyes that were saved. RESULTS: Twenty-two patients with Paecilomyces corneal or scleral infection with no significant history of trauma or surgery were identified over a 20-year period. Two distinct clinical presentations were noted with 17 presenting with corneal infection and 5 initially presenting with scleral infection, and all demonstrated a classical endothelial plaque and deep stromal infiltrate. Almost all required single or multiple anterior segment reconstructive surgeries together with systemic and topical antifungal agents. The first 10 patients were treated with amphotericin B, whereas the remaining 12 patients were treated with voriconazole and 21 of 22 patients underwent surgery. Paecilomyces spp. was identified from most intraocular specimens although corneal fungal growth was noted only from deep corneal biopsies or corneal buttons removed during corneal transplantation. Outcomes were better in the last 12 patients treated with voriconazole. CONCLUSIONS: Nontraumatic Paecilomyces anterior segment infection presents with a pathognomonic clinical picture when the cornea is the initial site of infection and later in scleral infections. Early identification and aggressive treatment with extirpative surgery and voriconazole may result in retention of the eye with useful vision.