Nina M. Clark

Antimicrobial resistance among gram-negative organisms in the intensive care unit

Purpose of reviewWe review the hospital-acquired gram-negative organisms commonly encountered among patients in the intensive care unit and discuss pertinent surveillance data, resistance mechanisms and patterns, and optimal treatment regimens for these pathogens. Recent findingsThere has been a notable increase in antibiotic resistance among gram-negative intensive care unit pathogens. Data from surveillance programs such as National Nosocomial Infections Surveillance System, Intensive Care Antimicrobial Resistance Epidemiology, and others have documented undesirable trends in antibiotic resistance, indicating decreasing efficacy of antibiotic classes such as third-generation cephalosporins, carbapenems, and fluoroquinolones, The increased prevalence of extended-spectrum &bgr;-lactamases has contributed to the finding of multidrug resistance among bacteria such as Klebsiella and Escherichia coli. Furthermore, organisms such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia display intrinsic resistance to many antibiotics, making selection of optimal therapy difficult. Studies have correlated infection by these organisms with prior antibiotic exposure, and containment of the spread of infection can be achieved by careful antibiotic use and infection control practices. SummaryAntibiotic resistance continues to rise among hospital-acquired gram-negative pathogens. Optimal management of these infections requires knowledge of local epidemiology and practices to control their spread.

Zygomycosis in Solid Organ Transplant Recipients: A Prospective, Matched Case-Control Study to Assess Risks for Disease and Outcome

BACKGROUND Clinical characteristics, risks, and outcomes in solid organ transplant (SOT) recipients with zygomycosis in the era of modern immunosuppressive and newer antifungal agent use have not been defined. METHODS In a matched case-controlled study, SOT recipients with zygomycosis were prospectively studied. The primary outcome measure was success (complete or partial response) at 90 days. RESULTS Renal failure (odds ratio [OR], 3.17; P = .010), diabetes mellitus (OR, 8.11; P < .001), and prior voriconazole and/or caspofungin use (OR, 4.41; P = .033) were associated with a higher risk of zygomycosis, whereas tacrolimus (OR, 0.23; P = .002) was associated with a lower risk of zygomycosis. Liver transplant recipients were more likely to have disseminated disease (OR, 5.48; P = .021) and developed zygomycosis earlier after transplantation than did other SOT recipients (median, 0.8 vs 5.7 months; P < .001). Overall the treatment success rate was 60%. Renal failure (OR, 11.3; P = .023) and disseminated disease (OR, 14.6; P = .027) were independently predictive of treatment failure, whereas surgical resection was associated with treatment success (OR, 33.3; P = .003). The success rate with liposomal amphotericin B was 4-fold higher even when controlling for the aforementioned variables. CONCLUSIONS The risks identified for zygomycosis and for disseminated disease, including those that were previously unrecognized, have implications for further elucidating the biologic basis and for optimizing outcomes in SOT recipients with zygomycosis.

Rapid development of Acinetobacter baumannii resistance to tigecycline

A 53‐year‐old woman experienced a multidrug‐resistant (MDR) Acinetobacter baumannii urinary tract infection 5 months after undergoing kidney and liver transplantation. The tigecycline minimum inhibitory concentration (MIC) for her A. baumannii isolate was 1.5 μg/ml; the patient received 2 weeks of therapy with intravenous tigecycline as a 100‐mg loading dose followed by 50 mg every 12 hours, with no lapses in treatment and with resolution of the infection. Three weeks later, MDR A. baumannii was isolated from her sputum in the setting of clinical evidence of pneumonia, and tigecycline was restarted; the tigecycline MIC for the A. baumannii isolate was 2 μg/ml. At approximately the same time, the patient was found to have a paraspinal abscess and spinal osteomyelitis. Cultures of the abscess fluid grew A. baumannii with a tigecycline MIC of 24 μg/ml. A follow‐up sputum culture again yielded A. baumannii, but with a tigecycline MIC of 24 μg/ml. Urine culture at that time also grew A. baumannii with a tigecycline MIC of 24 μg/ml. Clinicians should be aware that tigecycline MICs for A. baumannii isolates may increase during therapy with tigecycline after only brief exposure to the drug. Patients receiving tigecycline for Acinetobacter should be monitored for the development of clinical resistance, and isolates should be monitored for evidence of microbiologic resistance.

Infectious complications associated with the use of rituximab for ABO-incompatible and positive cross-match renal transplant recipients

Abstract:  Immunosuppressive protocols for ABO‐incompatible (ABOI) and positive cross‐match (PCM) solid organ transplant (SOT) recipients have included the use of rituximab (RTX). Infectious complications (IC) have been reported after the use of RTX for other indications, but have not been well studied in the SOT population. We performed a retrospective review of IC occurring within six months of ABOI and PCM renal transplantation (RT) in recipients receiving RTX. Medical records were reviewed for bloodstream, lung, gastrointestinal tract, allograft, or soft tissue infection. Between July 2001 and December 2004, 34 ABOI or PCM RT were performed at University of Illinois at Chicago, 25 of which received RTX with plasmapheresis and antithymocyte globulin (ATG) (eight ABOI and 17 PCM). Among the RTX recipients, the rate of IC was 48% compared with 11% among historical controls who did not receive RTX (p = 0.107). There were 21 episodes of IC in 13 patients including skin and soft tissue infection (8), bloodstream infection (5), esophagitis (3), peritonitis (3), pneumonia (1), and colitis (1). There was no difference in the rate of rejection, graft survival or patient survival between the two groups. These data suggest that there is a trend toward an increased rate of IC with RTX therapy in ABOI and PCM RT recipients.

Influenza: Epidemiology, Clinical Features, Therapy, and Prevention

Influenza A and B are important causes of respiratory illness in all age groups. Influenza causes seasonal outbreaks globally and, less commonly, pandemics. In the United States, seasonal influenza epidemics account for >200,000 hospitalizations and >30,000 deaths annually. More than 90% of deaths occur in the elderly population. Interestingly, in the novel 2009 H1N1 influenza pandemic, attack rates were highest among children and young adults. Fewer than 10% of cases occurred in adults >60 years old, likely because preexisting antibodies against other H1N1 viruses afforded protection. Despite concerns about a high lethality rate with the novel 2009 H1N1 strain, most illnesses caused by the 2009 H1N1 viruses were mild (overall case fatality rate <0.5%). Clinical features of influenza infection overlap with other respiratory pathogens (particularly viruses). The diagnosis is often delayed due to low suspicion and the limited use of specific diagnostic tests. Rapid diagnostic tests are widely available and allow detection of influenza antigen in respiratory secretions within 1 hour; however, sensitivity ranges from 50 to 90%. Neuraminidase inhibitors (NAIs) (eg, oseltamivir and zanamivir) are effective for treating influenza A or B and for prophylaxis in selected adults and children. Resistance to NAIs is rare, but influenza strains resistant to oseltamivir have been detected. Vaccines are the cornerstone of influenza control. Currently, trivalent inactivated vaccine (TIV) and live attenuated influenza vaccine (LAIV) are available. These agents reduce mortality and morbidity in high-risk patients (i.e., the elderly or patients with comorbidities), and expanding the use of vaccines to healthy children and adults reduces the incidence of influenza, pneumonia, and hospitalizations due to respiratory illnesses in the community.

Evolution of antimicrobial resistance among Enterobacteriaceae (focus on extended spectrum β-lactamases and carbapenemases)

Introduction: Bacteria within the family Enterobacteriaceae are important pathogens in nosocomial and community settings. Over the past two decades, antimicrobial resistance among Enterobacteriaceae dramatically escalated worldwide. The authors review the mechanisms of antimicrobial resistance among Enterobacteriaceae, epidemiology and global spread of resistance elements and discuss therapeutic options. Areas covered: An exhaustive search for literature relating to Enterobacteriaceae was performed using PubMed, using the following key words: Enterobacteriaceae; Klebsiella pneumoniae; Escherichia coli; antimicrobial resistance; plasmids; global epidemiology; carbapenemases (CPEs); extended spectrum β-lactamases (ESBLs) and multidrug resistance (MDR). Expert opinion: Enterobacteriaceae are inhabitants of intestinal flora and spread easily among humans (via hand carriage, contaminated food or water or environmental sources). Antimicrobial resistance may develop via plasmids, transposons or other mobile resistance elements. Mutations conferring resistance typically increase over time; the rate of increase is amplified by selection pressure from antibiotic use. Factors that enhance spread of antimicrobial resistance include: crowding; lack of hygiene; overuse and over-the-counter use of antibiotics; tourism; refugees and international travel. Clonal spread of resistant organisms among hospitals, geographic regions and continents has globally fueled the explosive rise in resistance. The emergence and widespread dissemination of MDR clones containing novel resistance elements (particularly ESBLs and CPEs) has greatly limited therapeutic options. In some cases, infections due to MDR Enterobacteriaceae are untreatable with existing antimicrobial agents. The authors discuss current and future therapeutic options for difficult-to-treat infections due to these organisms.

A multicenter study of histoplasmosis and blastomycosis after solid organ transplantation

S.A. Grim, L. Proia, R. Miller, M. Alhyraba, A. Costas‐Chavarri, J. Oberholzer, N.M. Clark. A multicenter study of histoplasmosis and blastomycosis after solid organ transplantation.
Transpl Infect Dis 2011. All rights reserved

Timing of susceptibility-based antifungal drug administration in patients with Candida bloodstream infection: correlation with outcomes

OBJECTIVES We sought to determine the impact of timing of appropriate antifungal therapy, as assessed by susceptibility results, on patient survival. METHODS Patients ≥16 years of age with first episodes of candidaemia during 2001-09 were included. Clinical data were collected retrospectively, including time to appropriate antifungal therapy and patient survival. RESULTS The study population included 446 patients [243 (54%) female, mean age 53 years] with candidaemia, 380 (85%) of whom had antifungal susceptibility data. Candida albicans was the most common pathogen (221, 50%) followed by Candida glabrata (99, 22%), Candida parapsilosis (59, 13%), Candida tropicalis (48, 11%) and Candida krusei (6, 1%). Appropriate antifungal therapy consisted of fluconazole (177, 40%), an echinocandin (125, 28%), amphotericin B (41, 9%) and voriconazole (6, 1%); 97 (22%) failed to receive appropriate antifungal therapy. The 30 day mortality was 34% (151/446) and there was no clear relationship between time from positive culture to receipt of appropriate antifungal therapy and 30 day survival. On multivariable Cox regression, increased APACHE II score [hazard ratio (HR) 1.11, 95% CI 1.09-1.13, P<0.001], cirrhosis (HR 2.15, 95% CI 1.48-3.13, P<0.001) and HIV infection (HR 2.03, 95% CI 1.11-3.72, P=0.02) were independent predictors of mortality. A secondary analysis requiring patients in the early treatment group to have received ≥24 h of effective antifungal therapy did show a significant mortality benefit to receiving antifungal treatment within 72 h of a positive blood culture being drawn (30 day mortality for early treatment: 27% versus 40%, P=0.004; HR for mortality with delayed treatment on multivariable analysis: 1.41, 95% CI 1.01-1.98, P=0.045). CONCLUSIONS Candida bloodstream infection is associated with high mortality, despite timely receipt of appropriate antifungal therapy.

Aeromonas Infection of the Hepatobiliary System: Report of 15 Cases and Review of the Literature

Aeromonas species cause both intestinal and extraintestinal disease. We reviewed hospital laboratory and medical records to identify patients with Aeromonas infection of the hepatobiliary or pancreatic system. Analysis of data from our hospital, as well as a review of the published literature, yielded a total of 41 episodes in 39 patients, and the features of these episodes are described. The most common manifestation of Aeromonas hepatobiliary infection among all reported cases was cholangitis (29 of 41 episodes). The majority of infections in our hospital occurred in patients with underlying immunosuppression or malignancy (13 of 15 patients), including 4 liver transplant recipients, and nosocomial infection was not infrequent (8 of 17 episodes). Infection occurred most commonly in patients with obstruction of the biliary tract due to stones, tumor, or stricture and was associated with a relatively high mortality rate (11.8%). Antibiotic susceptibility testing revealed that gentamicin, imipenem, and ciprofloxacin had the highest activity against the Aeromonas species isolated.

Pulmonary zygomycosis in solid organ transplant recipients in the current era.

Fifty‐eight solid organ transplant recipients with zygomycosis were studied to assess the presentation, radiographic characteristics, risks for extra‐pulmonary dissemination and mortality of pulmonary zygomycosis. Pulmonary zygomycosis was documented in 31 patients (53%) and developed a median of 5.5 months (interquartile range, 2–11 months) posttransplantation. In all, 74.2% (23/31) of the patients had zygomycosis limited to the lungs and 25.8% (8/31) had lung disease as part of disseminated zygomycosis; cutaneous/soft tissue (50%, 4/8) was the most common site of dissemination. Pulmonary disease presented most frequently as consolidation/mass lesions (29.0%), nodules (25.8%) and cavities (22.6%). Patients with disseminated disease were more likely to have Mycocladus corymbifer as the causative pathogen. The mortality rate at 90 days after the treatment was 45.2%. In summary, pulmonary zygomycosis is the most common manifestation in solid organ transplant recipients with zygomycosis, and disseminated disease often involves the cutaneous/soft tissue sites but not the brain.