Lisa L. Dever

Colistin- and Carbapenem-Resistant Escherichia coli Harboring mcr-1 and blaNDM-5, Causing a Complicated Urinary Tract Infection in a Patient from the United States

ABSTRACT Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States. Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States. Here, we report the isolation and identification of an Escherichia coli strain harboring both mcr-1 and carbapenemase gene blaNDM-5 from a urine sample in a patient without recent travel outside the United States. The isolate exhibited resistance to both colistin and carbapenems, but was susceptible to amikacin, aztreonam, gentamicin, nitrofurantoin, tigecycline, and trimethoprim-sulfamethoxazole. The mcr-1- and blaNDM-5-harboring plasmids were completely sequenced and shown to be highly similar to plasmids previously reported from China. The strain in this report was first isolated in August 2014, highlighting an earlier presence of mcr-1 within the United States than previously recognized. IMPORTANCE Colistin has become the last line of defense for the treatment of infections caused by Gram-negative bacteria resistant to multiple classes of antibiotics, in particular carbapenem-resistant Enterobacteriaceae (CRE). Resistance to colistin, encoded by the plasmid-borne gene mcr-1, was first identified in animal and clinical samples from China in November 2015 and has subsequently been reported from numerous other countries. In April 2016, mcr-1 was identified in a carbapenem-susceptible Escherichia coli strain from a clinical sample in the United States, followed by a second report from a carbapenem-susceptible E. coli strain originally isolated in May 2015. We report the isolation and identification of an E. coli strain harboring both colistin (mcr-1) and carbapenem (blaNDM-5) resistance genes, originally isolated in August 2014 from urine of a patient with recurrent urinary tract infections. To our knowledge, this is the first report in the United States of a clinical bacterial isolate with both colistin and carbapenem resistance, highlighting the importance of active surveillance efforts for colistin- and carbapenem-resistant organisms. Colistin has become the last line of defense for the treatment of infections caused by Gram-negative bacteria resistant to multiple classes of antibiotics, in particular carbapenem-resistant Enterobacteriaceae (CRE). Resistance to colistin, encoded by the plasmid-borne gene mcr-1, was first identified in animal and clinical samples from China in November 2015 and has subsequently been reported from numerous other countries. In April 2016, mcr-1 was identified in a carbapenem-susceptible Escherichia coli strain from a clinical sample in the United States, followed by a second report from a carbapenem-susceptible E. coli strain originally isolated in May 2015. We report the isolation and identification of an E. coli strain harboring both colistin (mcr-1) and carbapenem (blaNDM-5) resistance genes, originally isolated in August 2014 from urine of a patient with recurrent urinary tract infections. To our knowledge, this is the first report in the United States of a clinical bacterial isolate with both colistin and carbapenem resistance, highlighting the importance of active surveillance efforts for colistin- and carbapenem-resistant organisms.

Telithromycin: a new ketolide antimicrobial for treatment of respiratory tract infections

Telithromycin is a new ketolide antimicrobial, specifically developed for the treatment of community-acquired respiratory tract infections. It has a wide spectrum of antibacterial activity against common respiratory pathogens including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes. It also has activity against atypical pathogens, such as Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae. Telithromycin maintains activity against β-lactam and macrolide-resistant respiratory tract pathogens and does not appear to induce cross-resistance to other members of the macrolide-lincosamide-streptogramin (MLS) group of antimicrobials. It demonstrates bactericidal activity against S. pneumoniae and H. influenzae and has a prolonged concentration-dependent post-antibiotic effect (PAE) in vitro. The drug has favourable pharmacokinetics following oral administration. It is well absorbed, achieves good plasma levels and is highly concentrated in pulmonary tissues and white blood cells. In clinical trials, telithromycin given orally at a dose of 800 mg once daily for 5 - 10 days was as effective as comparator antimicrobials for the treatment of adults with community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute maxillary sinusitis and group A-β-haemolytic streptococcal pharyngitis or tonsillitis. The adverse events and safety profile were similar to comparator antimicrobials. The most common adverse events were diarrhoea, nausea, headache and dizziness. Telithromycin should provide an effective, convenient and well-tolerated once-daily oral therapy for treatment of respiratory infections.

Impact of adding maraviroc to antiretroviral regimens in patients with full viral suppression but impaired CD4 recovery

We reviewed the effect of adding maraviroc on CD4 cell counts in nine patients on antiretroviral therapy with full viral suppression but impaired CD4 cell recovery. There were no significant differences in changes in CD4 cell count, percentage of CD4 cells, or in the ratio of CD4/CD8 cells at 30 days and 25 weeks of maraviroc therapy. Plasma endotoxin levels measured in four patients before and during maraviroc treatment also showed no significant differences.

Antibiotics in the treatment of acute exacerbations of chronic bronchitis

The benefit of antimicrobial therapy for patients with an acute exacerbation of chronic bronchitis (AECB) remains controversial for two main reasons. First, the distal airways of patients with chronic bronchitis are persistently colonised, even during clinically stable periods, with the same bacteria that have been associated with AECB. Second, bacterial infection is only one of several causes of AECB. These factors have led to conflicting analyses on the role of bacterial agents and the response to antimicrobial therapy of patients with AECB. An episode of AECB is said to be present when a patient with chronic obstructive pulmonary disease (COPD) experiences some combination of increased dyspnoea, increased sputum volume, increased sputum purulence and worsening lung function. While the average COPD patient experiences 2 – 4 episodes of AECB per year, some patients, particularly those with more severe airway obstruction, are more susceptible to these attacks than others. Bacterial agents appear to be particularly associated with AECB in patients with low lung function and those with frequent episodes accompanied by purulent sputum. Non-typeable Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis account for up to 50% of episodes of AECB. Gram-negative bacilli are more likely to occur in patients with more severe lung disease. Antibiotics have been used to ameliorate AECB, to prevent AECB and to prevent the long-term loss of lung function that characterises COPD. Numerous prevention trials have been conducted with fairly consistent results; antibiotics do not lessen the number of episodes of AECB but do reduce the number of days lost from work. Most antibiotic trials have studied the impact of treatment on episodes of AECB and results have been inconsistent, largely due to patient selection and end point definition. In patients with severe airway obstruction, especially in the presence of purulent sputum, antibiotic therapy significantly shortens the duration of symptoms and can be cost-effective. Over the past 50 years, virtually all classes of antimicrobial agents have been studied in AECB. Important considerations include penetration into respiratory secretions, spectrum of activity and antimicrobial resistance. These factors limit the usefulness of drugs such as amoxicillin, erythromycin and trimethoprim-sulfamethoxazole. Extended-spectrum oral cephalosporins, newer macrolides and doxycycline have demonstrated efficacy in clinical trials. Amoxicillin-clavulanate and flouoroquinolones should generally be reserved for patients with more severe disease. A number of investigational agents, including ketolides and newer quinolones, hold promise for treatment of AECB.

Clostridium difficile - Associated Diarrhea in a VA Medical Center Clustering of Cases, Association With Antibiotic Usage, and Impact on HIV-infected Patients

A case-control study of patients with stools assayed for Clostridium difficile toxin over a 24-month period at a Veterans Affairs hospital found that the majority of cases (70.6%) occurred in temporal clusters. Clustering was particularly evident on a designated human immunodeficiency virus (HIV) unit. Thirty-four (75.5%) of 45 HIV-infected patients with C difficile-associated diarrhea (CDAD) died during their hospitalization. Third-generation cephalosporins were the antibiotics most strongly associated with CDAD.

Daptomycin and Rifampin for the Treatment of Methicillin-Resistant Staphylococcus aureus Septic Pulmonary Emboli in the Absence of Endocarditis

Daptomycin has demonstrated clinical efficacy in the treatment of methicillin-resistant Staphylococcus aureus-associated bacteremia and right-sided infective endocarditis. Although daptomycin is not approved for treatment of gram-positive pneumonia, clinical evidence suggests that it may be effective therapy for S. aureus-associated septic pulmonary emboli (SPE). We present our clinical experience with the use of daptomycin in combination with rifampin in four patients with SPE in the absence of infective endocarditis. Three of the patients had a history of injection drug use; two of these patients also had soft-tissue infections. All patients had clinical resolution of their infections. Daptomycin and rifampin appear to have a role in the treatment of methicillin-resistant S. aureus bacteremia with SPE in the absence of infective endocarditis and should be considered in patients that have failed therapy with vancomycin.

Molecular Characterization of an Early Invasive Staphylococcus epidermidis Prosthetic Joint Infection

Historically regarded as a skin commensal, Staphylococcus epidermidis has been increasingly implicated in invasive foreign body infections such as catheter-related bloodstream infections, indwelling device infections, and prosthetic joint infections. We report a case of an aggressive, difficult-to-eradicate, invasive prosthetic hip infection occurring early after hardware implant and associated with a high-grade bacteremia and assess its salient molecular characteristics. The clinical and molecular characteristics of this isolate mirror the pathogenesis and persistence commonly seen with invasive methicillin-resistant S. aureus and may be attributed to the combination of resistance genes (SCCmec type IV), putative virulence factors (arcA and opp3a), cytolytic peptide production (α-type phenol-soluble modulins), and biofilm adhesion, interaction, and maturation (bhp, aap, and β-type phenol-soluble modulins).

Oropharyngeal histoplasmosis: The diagnosis lies in the biopsy

Histoplasma capsulatum, a dimorphic fungus found world-wide, is endemic to regions of the Mississippi and Ohio River valleys and portions of Central and South America. Initial infection can present with acute pulmonary symptoms or remain clinically asymptomatic, with disease course generally guided by degree of inoculum and underlying immunosuppression. A chronic, progressive course of weight loss, oral ulceration, and fatigue has been associated with elderly males. We present a 79-year-old man with a chronic, progressive course of oral lesions, odynophagia, and weight loss who was found to have histoplasmosis on oral biopsy performed for suspicions of oropharyngeal squamous cell carcinoma. Histoplasma urine antigen, serum complement fixation antibody titers, and fungal tissues were all negative despite validated sensitivities in the >90% range. Our case report highlights the critical role of tissue biopsy in establishing a diagnosis of oropharyngeal histoplasmosis.

Botulism-like symptoms in an immunocompetent patient with Clostridium subterminale bacteremia

Clostridium subterminale is a low virulence species of Clostridium that is an infrequent cause of human infections. We report a case of C. subterminale bacteremia in an immunocompetent patient who developed botulism-like symptoms.

Pulmonary Kaposi's sarcoma as the initial presentation of human immunodeficiency virus infection

Kaposis sarcoma (KS) usually presents in HIV-infected patients with cutaneous lesions that may advance to extensive visceral disease. There have been only a few documented cases in which the initial presentation of Kaposis sarcoma involved the bronchopulmonary system. We describe a newly diagnosed patient who presented with pulmonary KS as his initial presentation of the disease. Our report is intended to increase clinicians’ awareness that pulmonary Kaposis sarcoma should be considered in HIV-infected patients who present with respiratory symptoms, even if they do not manifest the typical mucocutaneous manifestations of KS or have low CD4 counts. Early diagnosis and therapy are essential in improving outcomes as this condition carries a high mortality.