Use of daptomycin for the treatment of methicillin-resistant coagulase-negative staphylococcal ventriculitis.

Coagulase-negative staphylococci (CoNS) are the main pathogens causing hospital-acquired external-ventricular-drain- (EVD-) and lumbar-drain- (LD-) associated meningitis and ventriculitis. The treatment of these infections can be challenging and may require combination of intraventricular and intravenous administration of antibiotics. Limited animal data demonstrate rapid daptomycin bactericidal activity, adequate penetration in the setting of inflamed meninges, and extended half-life in the ventricles Steenbergen et al. (2009). There are limited clinical data using daptomycin intravenously and/or intraventricularly for the treatment of central nervous system infections (CNS) Elvy et al. (2008), Stucki et al. (2007), Lee et al. (2008) and Wallace et al. (2009). We report here our experience in the treatment of an EVD-related infection.

Identification of CTX-M ß-lactamases among Escherichia coli from the community in New York City.

We have identified CTX-M group 1 ß-lactamases in 87% of community-acquired Escherichia coli isolates that produce extended-spectrum ß-lactamases, with the majority harboring CTX-M-15 and representing the ST131 clonal group. Seventy percent of CTX-M-bearing isolates were from urine specimens; a large proportion was nonsusceptible to levofloxacin, trimethoprim/sulfamethoxazole, and ß-lactam antimicrobials. Many patients were relatively youthful (41% ≤65 years old; youngest, age 32). Patients with symptomatic bacteriuria received drugs to which the organisms were susceptible, and most had favorable outcomes. Timely recognition of such isolates could help physicians choose more appropriate antibacterial therapy.

Polymyxin-resistant clinical isolates of Escherichia coli.

A surveillance study to identify patients from the community with Escherichia coli resistant to broad-spectrum cephalosporins discovered two isolates that were also resistant to polymyxin B and colistin. One isolate from a patient in the community and a second from a patient who received multiple courses of polymyxin B also possessed a CTX-M-15 enzyme. Resistance to cationic peptides in E. coli is unusual, and testing for susceptibility to these agents should be performed.

In vitro double and triple bactericidal activities of doripenem, polymyxin B, and rifampin against multidrug-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli.

In vitro double and triple bactericidal activities of doripenem, polymyxin B, and rifampin were assessed against 20 carbapenem-resistant clinical isolates with different mechanisms of carbapenem resistance. Bactericidal activity was achieved in 90% of all bacteria assayed using combinations of polymyxin B, doripenem, and rifampin against five each of the carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli isolates studied. Combinations with these antibacterials may provide a strategy for treatment of patients infected with such organisms.

Identification of CTX-M beta-lactamases in Escherichia coli from hospitalized patients and residents of long-term care facilities.

Bacteria harboring CTX-M extended-spectrum beta-lactamases (ESBLs) have been identified worldwide, with most reports coming from regions outside North America. We have identified CTX-M enzymes in 31% of ESBL-positive Escherichia coli isolates from our hospital and more than half (53%) of the isolates from associated long-term care facilities. Approximately 3/4 of all CTX-M-bearing isolates were from urine specimens, with a predominance of CTX-M-15. A large proportion of such isolates were nonsusceptible to levofloxacin, trimethoprim/sulfamethoxazole, and all beta-lactam antimicrobials with the exception of the carbapenems, requiring carbapenem therapy for acute urinary tract infection or urinary tract-related sepsis. CTX-M beta-lactamases have emerged within our location, and detection of bacteria harboring these enzymes in the clinical microbiology laboratory remains problematic because molecular methods are needed for their identification.

Antimicrobial resistance among and therapeutic options against gram-negative pathogens.

Gram-negative bacterial pathogens are a common cause of infection, and the prevalence and rates of resistance among these pathogens to existing antimicrobial agents are increasing. beta-Lactamase-mediated resistance is of particular concern. High-level resistance attributable to beta-lactamase expression alone or in combination with other mechanisms is becoming increasingly prevalent among Enterobacteriaceae and gram-negative nonfermenting organisms. Doripenem is a new carbapenem with strong coverage of difficult-to-treat gram-negative bacterial pathogens. Its activity against Pseudomonas aeruginosa exceeds that of other carbapenems, and it has equivalent activity against Acinetobacter species and most Enterobacteriaceae. Thus, doripenem may be valuable alone or in combination with other agents in the treatment of serious gram-negative infections.

Evaluation of vancomycin and daptomycin potency trends (MIC creep) against methicillin-resistant Staphylococcus aureus isolates collected in nine U.S. medical centers from 2002 to 2006.

Vancomycin MIC creep has been reported by some institutions but not confirmed in large surveillance studies. We evaluated the possible occurrence of MIC creep when testing vancomycin and daptomycin against methicillin (oxacillin)-resistant Staphylococcus aureus (MRSA) by using precise incremental reference MIC methods. Nine hospitals (one in each U.S. census region) randomly selected bloodstream MRSA strains (target, 40/year) from 2002 to 2006. MICs were determined by the reference broth microdilution method using incremental dilutions (eight for each log(2) dilution step). Isolates for which vancomycin MICs were >1 microg/ml were typed by pulsed-field gel electrophoresis (PFGE). The vancomycin MIC mode was either 0.625 microg/ml (for eight hospitals) or 0.813 microg/ml (for one hospital), and vancomycin MIC results for 72.9% of strains were between 0.563 and 0.688 microg/ml. No yearly variation in the central tendency of vancomycin MICs for the wild-type population in any medical center was observed; however, when data were analyzed by the geometric mean statistic, vancomycin MIC increases (at three sites) and declines (at three sites) were observed. The daptomycin MIC mode varied from 0.156 microg/ml (2003 to 2005) to 0.219 microg/ml (2002 and 2006), and MIC results for 83.5% (80.3 to 89.2% in each of the centers) of isolates fell between these values. Among PFGE-typed strains, 43 of 55 (78%; from seven hospitals) showed a pattern consistent with that of the USA100 clone, which was represented by all strains from two hospitals and 64 to 88% of strains from five other medical centers; only one strain (2%) was USA300. In conclusion, the perception of MIC creep may vary according to the methods used to analyze the data. Geometric mean MIC data revealed a possible, very-low-level MIC creep at three of nine sites over the 5-year period, which was not evident using modal MICs or the data from all nine hospitals (+0.02 mug/ml). The occurrence of isolates for which the vancomycin MIC was >1 microg/ml was very unusual, with no increased trend, but these organisms were usually clonal (USA100).

Health care-associated infection (HAI): a critical appraisal of the emerging threat-proceedings of the HAI Summit.

During the Health Care-Associated Pneumonia Summit conducted in June 2007, it was found that there is a need for educational efforts in several areas of health care-associated infections (HAI) that extend beyond pneumonia. This supplement to Clinical Infectious Diseases represents the proceedings of the HAI Summit, a diverse panel of clinical investigators whose goal was to assess the quality of evidence regarding issues surrounding HAI and to discuss potential implications for its diagnosis and treatment in the future.

The role of carbapenems in initial therapy for serious Gram-negative infections.

The treatment of patients with serious Gram-negative infections must be both prompt and correct. Numerous studies have demonstrated that mortality risk is significantly increased when the initial antibiotic regimen does not adequately cover the infecting pathogen. Furthermore, changing to an appropriate regimen once culture results are available does not reduce this risk. Therefore, one must empirically treat serious infections with a regimen that covers likely pathogens. Selecting such a regimen is complicated by the increasing prevalence of resistance to commonly used antibiotics. Moreover, multidrug-resistant pathogens, once limited to hospital-acquired infections, are increasingly being detected in community-acquired infections, especially those involving the urinary and gastrointestinal tracts or in immunocompromised patients. Consequently, the initial antibiotic regimen must have a broad spectrum of activity that includes potential resistant pathogens, as indicated by the local antibiogram. Many multidrug-resistant pathogens remain susceptible to carbapenems despite increasing worldwide antibiotic resistance. This article reviews the role played by carbapenems in the initial treatment of serious Gram-negative infections and the potential effect of emerging resistance on this role.

Carbapenem-resistant Escherichia coli harboring Klebsiella pneumoniae carbapenemase beta-lactamases associated with long-term care facilities.

Nine carbapenem-resistant Escherichia coli isolates harboring Klebsiella pneumoniae carbapenemase (KPC)-2 or KPC-3 enzymes were identified in patients residing in 7 distinct long-term care facilities. Cefotaxime-hydrolyzing (CTX-M)-type beta-lactamases were also documented in 3 isolates. The identification of these enzymes in patients staying in long-term care facilities should be of great concern to all components of health care systems.

Impact of contact and droplet precautions on the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus infection.

OBJECTIVE: To evaluate the efficacy of contact and droplet precautions in reducing the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections. DESIGN: Before-after study.Setting. A 439-bed, university-affiliated community hospital. METHODS: To identify inpatients infected or colonized with MRSA, we conducted surveillance of S. aureus isolates recovered from clinical culture and processed by the hospital's clinical microbiology laboratory. We then reviewed patient records for all individuals from whom MRSA was recovered. The rates of hospital-acquired MRSA infection were tabulated for each area where patients received nursing care. After a baseline period, contact and droplet precautions were implemented in all intensive care units (ICUs). Reductions in the incidence of hospital-acquired MRSA infection in ICUs led to the implementation of contact precautions in non-ICU patient care areas (hereafter, "non-ICU areas"), as well. Droplet precautions were discontinued. An analysis comparing the rates of hospital-acquired MRSA infection during different intervention periods was performed. RESULTS: The combined baseline rate of hospital-acquired MRSA infection was 10.0 infections per 1,000 patient-days in the medical ICU (MICU) and surgical ICU (SICU) and 0.7 infections per 1,000 patient-days in other ICUs. Following the implementation of contact and droplet precautions, combined rates of hospital-acquired MRSA infection in the MICU and SICU decreased to 4.3 infections per 1,000 patient-days (95% confidence interval [CI], 0.17-0.97; P=.03). There was no significant change in hospital-acquired MRSA infection rates in other ICUs. After the discontinuation of droplet precautions, the combined rate in the MICU and SICU decreased further to 2.5 infections per 1,000 patient-days. This finding was not significant (P=.43). In the non-ICU areas that had a high incidence of hospital-acquired MRSA infection, the rate prior to implementation of contact precautions was 1.3 infections per 1,000 patient-days. After the implementation of contact precautions, the rate in these areas decreased to 0.9 infections per 1,000 patient-days (95% CI, 0.47-0.94; P=.02). CONCLUSION: The implementation of contact precautions significantly decreased the rate of hospital-acquired MRSA infection, and discontinuation of droplet precautions in the ICUs led to a further reduction. Additional studies evaluating specific infection control strategies are needed.

Identification of carbapenem-resistant klebsiella pneumoniae harboring KPC enzymes in New Jersey.

Klebsiella pneumoniae isolates harboring KPC enzymes have been identified in many geographical areas since 2001. Numerous problems exist in the detection and treatment of patients with such isolates. The clinical characteristics and molecular epidemiology associated with 12 randomly chosen patients in whom these enzymes were detected by molecular methods are described. This is the first description of the identification of carbapenem-resistant K. pneumoniae isolates harboring KPC beta-lactamases at the Veterans Administration Hospital in New Jersey (VA NJHCS). Because recognition of carbapenem resistance in K. pneumoniae due to KPC enzymes can only be achieved by molecular methods, detection in the Clinical Microbiology Laboratory by routine methods will continue to be difficult, leading to dilemmas in treatment.

Novel antibiotic combinations against infections with almost completely resistant Pseudomonas aeruginosa and Acinetobacter species.

For infections with antibiotic-susceptible strains of Pseudomonas aeruginosa, most studies have suggested that combination therapy, usually with a beta -lactam antibiotic plus an aminoglycoside, is preferable for patients with bacteremia and neutropenia. Against infections with Pseudomonas aeruginosa or Acinetobacter baumannii isolates that are resistant to all antibiotics except the polymyxins, several novel antibiotic combinations demonstrate increased activity in vitro compared with that of any single agent. Whether these combinations yield outcomes that are improved over those seen with a polymyxin or other agent alone remains to be determined. However, against infections with species resistant to all antibiotics, including polymyxins, novel combinations are the only remaining therapeutic option.

Fluoroquinolone-resistant Streptococcus agalactiae: epidemiology and mechanism of resistance.

Quinolone-resistant Streptococcus agalactiae bacteria were recovered from single-patient isolates and found to contain mutations in the gyrase and topoisomerase IV genes. Pulsed-field gel electrophoresis demonstrated that four isolates from the same long-term care facility were closely related; in seven cases, quinolone-resistant Haemophilus influenzae and S. agalactiae bacteria were isolated from the same patient.

Increased mortality associated with a clonal outbreak of ceftazidime-resistant Klebsiella pneumoniae: a case-control study.

OBJECTIVES: To determine risk factors for ceftazidime-resistant Klebsiella pneumoniae infection and the effect of ceftazidime-resistant K. pneumoniae infection on mortality during an isolated outbreak. DESIGN: Case-control investigation using clinical and molecular epidemiology and prospective analysis of infection control interventions. SETTING: Surgical intensive care unit of a university-affiliated community hospital. PATIENTS: Fourteen case-patients infected with ceftazidime-resistant K. pneumoniae and 14 control-patients. RESULTS: Ten of 14 case-patients had identical strains by pulsed-field gel electrophoresis. Broad-spectrum antibiotic therapy before admission to the unit was strongly predictive of subsequent ceftazidime-resistant K. pneumoniae infection. In addition, patients with ceftazidime-resistant K. pneumoniae infection experienced increased mortality (odds ratio, 3.77). CONCLUSIONS: Cephalosporin restriction has been shown to decrease the incidence of nosocomial ceftazidime-resistant K. pneumoniae. However, isolated clonal outbreaks may occur due to lapses in infection control practices. Reinstatement of strict handwashing, thorough environmental cleaning, and repeat education led to termination of the outbreak. A distinct correlation between ceftazidime-resistant K. pneumoniae infection and mortality supports the important influence of antibiotic resistance on the outcome of serious bacterial infections.

Quinolone-resistant Haemophilus influenzae: determination of mutant selection window for ciprofloxacin, garenoxacin, levofloxacin, and moxifloxacin.

Stepwise selection of ciprofloxacin-resistant Haemophilus influenzae mutants produced first-, second-, third-, and fourth-step substitutions in GyrA (S84Y), ParC (S84R), GyrA (D88N), and ParC (E88K), respectively. Successive mutations raised the mutant selection window. The wild-type selection window for garenoxacin, levofloxacin, and moxifloxacin was also measured.

Quinolone-resistant Haemophilus influenzae in a long-term-care facility: nucleotide sequence characterization of alterations in the genes encoding DNA gyrase and DNA topoisomerase IV.

Fluoroquinolone-resistant isolates of Haemophilus influenzae, obtained from a long-term care facility, were examined for nucleotide sequence differences in the quinolone-resistance-determining regions of gyrA, gyrB, parC, and parE. Similarities among the resistant isolates, plus multiple differences with susceptible isolates, suggest clonal dissemination involving two resistant subclones.

Effect of interferon-alpha2b therapy on St. Louis viral meningoencephalitis: clinical and laboratory results of a pilot study.

The safety and potential efficacy of interferon (IFN)-alpha2b were determined for 15 patients during an outbreak of meningoencephalitis due to St. Louis encephalitis (SLE) virus. Clinical and laboratory results were compared with those of 17 untreated patients who were admitted to the same hospital during this nonrandomized preliminary trial. Quadriplegia, quadriparesis, or respiratory insufficiency persisted after the first week of hospitalization, for 11 of 17 untreated patients and for only 2 of 15 treated patients. These complications existed after the second week of hospitalization for 5 of the 17 untreated patients and for 1 of the 15 treated patients. Transient neutropenia and/or mild hepatitis occurred in 11 treated patients. Early initiation of IFN-alpha2b therapy may reduce the severity and duration of complications due to previously untreatable flavivirus meningoencephalitis. A prospective randomized controlled trial is warranted.

Emergence of carbapenem-resistant Klebsiella species possessing the class A carbapenem-hydrolyzing KPC-2 and inhibitor-resistant TEM-30 beta-lactamases in New York City.

Nineteen isolates of carbapenem-resistant Klebsiella species were recovered from 7 hospitals in New York City. Most K. pneumoniae belonged to a single ribotype. Nucleotide sequencing identified KPC-2, a carbapenem-hydrolyzing beta -lactamase. In 3 strains, TEM-30, an inhibitor-resistant beta -lactamase, was detected. Carbapenem-resistant Klebsiella species possessing KPC-2 are endemic in New York City. This study documents the identification of an inhibitor-resistant TEM beta -lactamase in the United States.