Monica M. Lahra

Survival after pulmonary edema due to enterovirus 71 encephalitis

Background: A distinctive pattern of enterovirus 71 (EV71) infection, characterized by fever, exanthem, acute pulmonary edema (PE), brainstem encephalitis, and flaccid paresis, affects infants and young children. Most die rapidly owing to respiratory failure and fulminant PE. Method: The authors report short- and long-term outcome of six survivors of the acute illness. Results: In the context of acute PE and widespread weakness, recognition of the underlying neurologic disorder was facilitated by the distinctive pattern of MRI signal abnormalities in posterior pons and medulla. EV71-specific PCR of clinical samples helped confirm the diagnosis. Acute PE was managed with mechanical ventilation, afterload reduction, and inotrope support, and resolved completely over days. One patient with minimal neurologic recovery died 9 weeks after disease onset. The other patients have residual neurologic dysfunction, varying from subtle monoparesis to severe bulbar dysfunction, central and peripheral respiratory failure, and flaccid quadriparesis. Faster neurologic recovery was associated with less long-term deficit. Long-term outcome was similar in patients treated with and without pleconaril or IV immunoglobulin. Three long-term survivors treated with IV corticosteroids had less severe long-term neurologic disability than two not treated with steroids. Conclusion: Acute pulmonary edema and encephalomyelitis occurs with EV71 infection in infants. Long-term neurologic outcome varied from minor, focal weakness to profound, global motor dysfunction with respiratory failure.

The ticking time bomb: escalating antibiotic resistance in Neisseria gonorrhoeae is a public health disaster in waiting

From a once easily treatable infection, gonorrhoea has evolved into a challenging disease, which in future may become untreatable in certain circumstances. International spread of extensively drug-resistant gonococci would have severe public health implications. It seems clear that under the current treatment pressure from extended-spectrum cephalosporins, and owing to Neisseria gonorrhoeaes remarkable evolutionary adaptability, further rise of ceftriaxone-resistant strains around the world is inevitable. Simply increasing the doses of extended-spectrum cephalosporins will likely prove ineffective in the long run, and has been a lesson learnt for all single-agent therapies used for gonorrhoea to date. We recommend that dual therapy, especially those consisting of extended-spectrum cephalosporins and azithromycin, be adopted more widely and complemented by strengthening of antimicrobial resistance surveillance. Unless there is urgent action at international and local levels to combat the problem of N. gonorrhoeae antimicrobial resistance, we are in for gloomy times ahead in terms of gonorrhoea disease and control.

Molecular approaches to enhance surveillance of gonococcal antimicrobial resistance

The best available data indicate that the world is heading towards a pandemic of extensively drug-resistant Neisseria gonorrhoeae. At the same time, clinical microbiology laboratories have moved away from using culture-based methods to diagnose gonorrhoea, thus undermining our ability to detect antimicrobial resistance (AMR) using current technologies. In this Opinion article, we discuss the problem of N. gonorrhoeae AMR, particularly emerging resistance to the cephalosporin ceftriaxone, outline current concerns about the surveillance of N. gonorrhoeae AMR and propose the use of molecular methods on a large scale to systematically enhance surveillance.

A New Multidrug-Resistant Strain of Neisseria gonorrhoeae in Australia

A young woman with a vaginal discharge was found by means of sensitivity testing and genetic analysis to have ceftriaxone-resistant Neisseria gonorrhoeae. The infection did not respond to ceftriaxone but was treated successfully with ceftriaxone plus azithromycin.

Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a call for international collaborative action

In a Policy Forum, Teodora Wi and colleagues discuss the challenges of antimicrobial resistance in gonococci.

Failure of 500 mg of ceftriaxone to eradicate pharyngeal gonorrhoea, Australia

been occurring since admission. On day 14, the patient developed leucocytosis and blood cultures were drawn, which grew MRSA. The MIC of vancomycin increased to 2 mg/L, with that of daptomycin remaining at 0.38 mg/L. Since the patient continued to be symptomatic, irrigation and debridement was scheduled, but due to surgeon availability issues this was not performed until hospital day 19. A sample was obtained during the procedure and cultured, and on day 22, after .2 weeks of treatment with daptomycin, MRSA grew with a daptomycin MIC of 3 mg/L [daptomycin-non-susceptible S. aureus (DNSSA)]. The primary cause of the daptomycin failure was most likely a delay in incision and drainage of the abscesses. Experimental osteomyelitis models have shown selective resistance with daptomycin monotherapy, 2 which possibly contributed to the resistance in this case. Daptomycin was discontinued and, unfortunately, vancomycin was restarted over the weekend. After the patient became bacteraemic on day 14, we recommended a TEE, which was ordered but not performed until day 23. Lesions were found on the left coronary cusp (LCC) and the tricuspid valve, consistent with endocarditis. Vancomycin was discontinued, since current expert opinion states alternative anti-microbials should be considered when the vancomycin MIC is ≥2 mg/L, due to treatment failures. 3,4 Considering this and the severity of infection in this patient, we turned to salvage therapy options and ceftaroline (600 mg intravenously every 12 h), which had an Etest MIC of 0.5 mg/L, was chosen. Ceftaroline is a fifth-generation cephalosporin with activity against MRSA. Ceftaroline was chosen for a number of reasons. First, it is rapidly bactericidal. Ho et al. 5 reported sterilization in 13 days in a case of endocarditis. Also, the incidence of thrombo-cytopenia with long-term use is low, which was particularly important since our patient had a history of thrombocytopenia secondary to hepatitis. Finally, a literature search revealed a series of case reports showing successful use of ceftaroline in the treatment of MRSA endocarditis 5 and an experimental model demonstrating potential use in osteomyelitis. 6 Subsequent blood cultures drawn on days 29 and 32 were negative. On day 32, a repeat irrigation and debridement was performed. After 37 consecutive days of ceftaroline treatment, a TEE showed resolution of echodensities at the base of the tri-cuspid valve and a stable, fibronodular lesion on the LCC. Ceftaro-line was continued for a total of 44 days, with no further episodes of bacteraemia, leucocytosis or fever, …

Analytical Evaluation of GeneXpert CT/NG, the First Genetic Point-of-Care Assay for Simultaneous Detection of Neisseria gonorrhoeae and Chlamydia trachomatis

ABSTRACT GeneXpert CT/NG was evaluated with 372 characterized bacterial strains. Sensitivity of 10 genome copies/reaction was obtained for both agents. Four Neisseria mucosa and two Neisseria subflava isolates were positive for one of two gonococcal targets; however, the assay flagged all as negative. The assay was analytically highly sensitive and specific.

In Vitro Activity of Ertapenem versus Ceftriaxone against Neisseria gonorrhoeae Isolates with Highly Diverse Ceftriaxone MIC Values and Effects of Ceftriaxone Resistance Determinants: Ertapenem for Treatment of Gonorrhea?

ABSTRACT Clinical resistance to the currently recommended extended-spectrum cephalosporins (ESCs), the last remaining treatment options for gonorrhea, is being reported. Gonorrhea may become untreatable, and new treatment options are crucial. We investigated the in vitro activity of ertapenem, relative to ceftriaxone, against N. gonorrhoeae isolates and the effects of ESC resistance determinants on ertapenem. MICs were determined using agar dilution technique or Etest for international reference strains (n = 17) and clinical N. gonorrhoeae isolates (n = 257), which included the two extensively drug-resistant (XDR) strains H041 and F89 and additional isolates with high ESC MICs, clinical ESC resistance, and other types of clinical high-level and multidrug resistance (MDR). Genetic resistance determinants for ESCs (penA, mtrR, and penB) were sequenced. In general, the MICs of ertapenem (MIC50 = 0.032 μg/ml; MIC90 = 0.064 μg/ml) paralleled those of ceftriaxone (MIC50 = 0.032 μg/ml; MIC90 = 0.125 μg/ml). The ESC resistance determinants mainly increased the ertapenem MIC and ceftriaxone MIC at similar levels. However, the MIC ranges for ertapenem (0.002 to 0.125 μg/ml) and ceftriaxone (<0.002 to 4 μg/ml) differed, and the four (1.5%) ceftriaxone-resistant isolates (MIC = 0.5 to 4 μg/ml) had ertapenem MICs of 0.016 to 0.064 μg/ml. Accordingly, ertapenem had in vitro advantages over ceftriaxone for isolates with ceftriaxone resistance. These in vitro results suggest that ertapenem might be an effective treatment option for gonorrhea, particularly for the currently identified ESC-resistant cases and possibly in a dual antimicrobial therapy regimen. However, further knowledge regarding the genetic determinants (and their evolution) conferring resistance to both antimicrobials, and clear correlates between genetic and phenotypic laboratory parameters and clinical treatment outcomes, is essential.

Neisseria gonorrhoeae isolates with high-level resistance to azithromycin in Australia

References 1 Ewers C, Stamm I, Pfeifer Y et al. Clonal spread of highly successful ST15-CTX-M-15 Klebsiella pneumoniae in companion animals and horses. J Antimicrob Chemother 2014; 69: 2676–80. 2 Ewers C, Bethe A, Stamm I et al. CTX-M-15-D-ST648 Escherichia coli from companion animals and horses: another pandemic clone combining multiresistance and extraintestinal virulence?. J Antimicrob Chemother 2014; 69: 1224–30. 3 Ewers C, Grobbel M, Stamm I et al. Emergence of human pandemic O25:H4-ST131 CTX-M-15 extended-spectrum-b-lactamase-producing Escherichia coli among companion animals. J Antimicrob Chemother 2010; 65: 651–60. 4 Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals—Third Edition: Approved Standard M31-A3. CLSI, Wayne, PA, USA, 2008.

Enhanced gonococcal antimicrobial surveillance in the era of ceftriaxone resistance: a real-time PCR assay for direct detection of the Neisseria gonorrhoeae H041 strain

OBJECTIVES Recent emergence of the extensively drug-resistant Neisseria gonorrhoeae H041 strain in Japan raises concerns that gonorrhoea may soon become untreatable and emphasizes the need for enhanced surveillance. In this study we developed a real-time PCR assay for direct detection of the H041 strain. METHODS Two real-time PCR assays for detection of the penA gene of the H041 strain, H041-PCR1 and H041-PCR2, were developed and evaluated in parallel. Assay performance was assessed using a panel of pathogenic and commensal Neisseria species (n = 167 strains) including the N. gonorrhoeae H041 strain and clinical specimens (n = 252) submitted for sexual health screening. The detection limits of the assays were compared with a standard N. gonorrhoeae real-time PCR method. RESULTS Both the H041-PCR1 and H041-PCR2 assays correctly detected the N. gonorrhoeae H041 strain and provided negative results for all other N. gonorrhoeae strains. However, only the H041-PCR2 assay proved to be specific when applied to the non-gonococcal Neisseria species and clinical samples. False-positive results in the H041-PCR1 included cross-reactions with two Neisseria subflava isolates and eight clinical specimens. DNA sequencing of these N. subflava strains revealed the presence of the penicillin-binding protein 2 Ala328Thr alteration previously only observed in the N. gonorrhoeae H041 strain. CONCLUSIONS The H041-PCR2 assay is suitable for direct detection of the N. gonorrhoeae H041 ceftriaxone-resistant strain in cultured and non-cultured samples.