Dual Antimicrobial Therapy Research Articles

2012 European guideline on the diagnosis and treatment of gonorrhoea in adults

Gonorrhoea is a major public health concern globally. Of particularly grave concern is that resistance to the extended-spectrum cephalosporins has emerged during the most recent years. This guideline provides recommendations regarding the diagnosis and treatment of gonorrhoea in Europe. Compared to the outdated 2009 European gonorrhoea guideline, this 2012 European gonorrhoea guideline provides up-to-date guidance on, broader indications for testing and treatment of gonorrhoea;the introduction of dual antimicrobial therapy (ceftriaxone 500 mg and azithromycin 2 g) for uncomplicated gonorrhoea when the antimicrobial sensitivity is unknown; recommendation of test of cure in all gonorrhoea cases to ensure eradication of infection and identify emerging resistance; and recommendations to identify, verify and report failures with recommended treatment regimens. Optimisations of the testing, diagnostics, antimicrobial treatment and follow-up of gonorrhoea patients are crucial in controlling the emergent spread of cephalosporin-resistant and multidrug-resistant gonorrhoea.

The ‘2012 European guideline on the diagnosis and treatment of gonorrhoea in adults’ recommends dual antimicrobial therapy

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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?

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 (MIC(50) = 0.032 μg/ml; MIC(90) = 0.064 μg/ml) paralleled those of ceftriaxone (MIC(50) = 0.032 μg/ml; MIC(90) = 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.

Hematogenous Osteomyelitis by Acinetobacter Baumannii: Case Report and Literature Review

Skeletal infection with Acinetobacter baumanii is a rare condition and found mainly among soldiers injured in war. Multidrug resistant (MDR) Acinetobacter baumanii (A. baumanii) osteomyelitis is difficult to treat and requires long course of intravenous antibiotics. Most of reported cases in the literature are the consequences of direct inoculation of the pathogen. Here in, we report the first case of A. Baumannii osteomyelitis disseminated through hematogenous route and the therapeutic approach for this rare infection. Clinical Presentation: A 46 year old African-American male patient with human immunodeficiency virus (HIV) and end- stage renal disease on hemodialysis, who developed persistent MDR A. baumanii bacteremia in the hospital, thought to be secondary to the hemodialysis catheter, necessitating replacement of the catheter. Three months after his discharge to a skilled nursing facility (SNF), he developed left leg swelling without noticeable pain or fever. MRI revealed findings consistent with chronic osteomyelitis of left tibia and intra operative bone culture grew MDR A. baumannii. The patient had good outcome after three surgical debridements and prolonged period (7 Months) of dual antimicrobial therapy. Discussion: While in most documented cases of A. baumannii osteomyelitis, entry appears to require direct inoculation; our case suggests that this pathogen can seed into bone hematogenously in the setting of immunosuppression, persistent bacteremia and possibly in the presence of underlying bone infarcts. Clinicians need to be aware of this rare possible consequence of A. baumannii bacteremia. In conclusion, combination of multiple surgical debridements and dual antimicrobial therapy for a long period may result in a good outcome.

Optimizing Empirical Antimicrobial Therapy for Infection due to Gram-Negative Pathogens in the Intensive Care Unit: Utility of a Combination Antibiogram

To determine whether the use of dual antimicrobial therapy based on the results of a combination antibiotic susceptibility report (antibiogram) increases the likelihood of selecting adequate empirical coverage in critically ill patients with infection due to potentially resistant gram-negative pathogens. Retrospective data analysis. Urban academic medical center. An analysis of culture results and susceptibility data from intensive care unit patients determined by the clinical microbiology laboratory was performed. The proportion of 5 common gram-negative pathogens susceptible to monotherapy with 1 of 3 antipseudomonal antibiotics (piperacillin-tazobactam, ceftazidime, or imipenem) was compared with the proportion susceptible to each of these 3 "backbone" agents plus 1 of 4 additional antimicrobial agents used in combination. More than 5,000 clinical isolates were examined. When all isolates recovered during the entire study period were included, the addition of any of the second antibiotics studied to each of the 3 backbone agents significantly increased the likelihood of covering the causative pathogen (P < .01 for each). The benefit of combination therapy was variable when results for each of the 5 organisms were examined individually. When temporal trends in susceptibility were examined, the decrease in the proportion of organisms susceptible to monotherapy was statistically significant for both imipenem and ceftazidime (P < .01). Reporting antibiotic susceptibility data in the form of a combination antibiogram may be useful to clinicians who are considering empirical antimicrobial therapy in the intensive care unit.

Identification of Optimal Combinations for Empirical Dual Antimicrobial Therapy of Pseudomonas aeruginosa Infection: Potential Role of a Combination Antibiogram

To better determine the optimal combinations for empirical dual antimicrobial therapy of Pseudomonas aeruginosa infection, we evaluated the utility of a novel combination antibiogram. Although the combination antibiogram allowed modest fine-tuning of choices for dual antibiotic therapy, selections based on the 2 antibiograms did not differ substantively. Drug combinations with the broadest coverage were consistently composed of an aminoglycoside and a beta-lactam.

Clinical aspiration-related practice patterns in the intensive care unit: a physician survey.

To characterize physician practice patterns regarding the clinical, microbiological, and antimicrobial-related events of suspected or documented aspiration and aspiration pneumonia within the intensive care unit. National mail survey. University medical center. Critical care physician members of the Society of Critical Care Medicine. Survey questionnaire. The response rate was 645 (32%) of 2,000 mailed surveys; analysis of data represents completed questionnaires from 605 respondents. Intensivists (42.3%), pulmonologists (22.6%), and surgeons (21.6%) represent the majority of respondents. Altered level of consciousness (67.9%) in the intensive care unit was identified as the predominant predisposing factor for aspiration pneumonia. Sixty-four percent of physicians used sputum specimens, rather than protected specimen brushes or bronchoalveolar lavage, as the diagnostic source of bacterial cultures in cases of suspected aspiration pneumonia. Microbiological assessment of aspiration pneumonia revealed the absence of any predominant pathogen, although Staphylococcus aureus and Pseudomonas aeruginosa were cited in 40.1% of combined responses, whereas anaerobes represented the fifth most prevalent cultured bacteria. In cases of suspected and confirmed aspiration, 51.9% and 77.7% of respondents, respectively, would prescribe an antimicrobial agent in the absence of a definitive infectious process, with administration of dual antimicrobial therapy increasing from 28.9% to 46.0% in suspected vs. confirmed cases of aspiration. In the treatment of aspiration pneumonia, 27.6% of physicians preferred pathogen-specific therapy, whereas the remainder (72.4%) selected an empirical antibiotic regimen based on prior clinical experience. Overall, a beta-lactam/beta-lactamase inhibitor, followed by a cephalosporin, aminoglycoside in combination, or clindamycin, was most often selected for empirical therapy of all defined aspiration-related clinical diagnoses. Our study revealed a divergent approach to antimicrobial treatment of cases of aspiration in the intensive care unit. Further investigation is warranted to determine why empirical antimicrobials are initiated frequently for noninfectious stages of aspiration.