Between and , acinetobacter species were the only .. forms provided by the authors are available with the full text of this article at Go to. Multidrug-resistant Acinetobacter baumannii (MDR-Ab) causes wound and bloodstream infections as well as ventilator-associated pneumonia. of human and animal origin in multiple countries (NEJM Journal Watch Acinetobacter spp., and Pseudomonas aeruginosa from inpatients.

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Hospital-acquired infections are a major challenge to patient safety. It is estimated that ina total of 1. Infections caused by gram-negative bacteria have features that are of particular concern. These organisms are highly efficient at up-regulating or acquiring genes that code for mechanisms of antibiotic drug resistance, especially in acintobacter presence of antibiotic selection pressure.

Furthermore, they have available to them a plethora of resistance mechanisms, often using multiple mechanisms against the same antibiotic or using a single mechanism to affect multiple antibiotics Fig.

Compounding the problem of antimicrobial-drug resistance is the immediate threat of a reduction in the discovery and development of new antibiotics. As a consequence, a perfect storm has been created with regard to these infections: Seven mechanisms of resistance are shown in the gram-negative bacterium, with some being mediated by a mobile plasmid.

Red spheres indicate antibiotics. Hospital-acquired infections are acinnetobacter commonly associated with invasive medical devices or surgical procedures.

Hospital-Acquired Infections Due to Gram-Negative Bacteria

Lower respiratory tract and bloodstream infections are the most lethal; however, urinary tract ainetobacter are the most common. Recent data from the U. Aacinetobacter pneumonia is the most common life-threatening hospital-acquired infection, and the majority of cases are acineobacter with mechanical ventilation.

In a recent survey, A more recent clinical entity that physicians need to be aware of aconetobacter health care—associated pneumonia — that is, cases of pneumonia acquired in the community by patients who have had direct or indirect contact with a health care or long-term care facility and are subsequently hospitalized.

Such patients are more likely to have a coexisting illness and to receive inactive empirical antibiotic therapy and are at greater risk for death than patients who have true community-acquired pneumonia.

Apart from being associated with increased morbidity and mortality, suspected acibetobacter pneumonia in the ICU can lead to the inappropriate use of antibiotic drugs, contributing to bacterial drug resistance and increases in toxic effects and health care costs.

To optimize the appropriateness of antibiotic use, physicians must be aware of the management paradigms for hospital-acquired pneumonia Table 2. The diagnosis of ventilator-associated pneumonia remains challenging, with no easily obtained reference standard. Apart from clinical criteria, microbiologic assessment is important to help guide therapy. For patients in whom ventilator-associated pneumonia is suspected, a sample from the lower respiratory tract should be obtained by means of endotracheal aspiration, bronchoalveolar lavage, or a protected specimen brush depending on the resources available 18 acinetobafter, 19 for microscopy and culture before antibiotics are administered.

Although each sampling method has its limitations, the most important point is to obtain the sample in a timely manner. The alternative nejmm appear to be associated with similar outcomes, on the basis acinetobacer recent systematic reviews. To assist the treating physician in determining whether a cultured organism signifies ainetobacter or infection, it has been recommended that quantitative cultures be obtained, either by measuring the colony-forming units CFU per milliliter or by grading the bacterial growth as light, moderate, or heavy semiquantified approach.

Quantitative culture results are subject to possible sampling variability, and there is no evidence that quantitative cultures, as compared with qualitative cultures, are associated with reductions in mortality, the length of the ICU stay, the duration of mechanical ventilation, or the need to adjust antibiotic therapy.

To further xcinetobacter such differentiation in patients with ventilator-associated pneumonia, promising biomarkers are being studied in combination with clinical and microbiologic factors. These biomarkers include procalcitonin, C-reactive protein, and soluble triggering receptor expressed on myeloid cells sTREM With a hospital stay of 5 days or longer, as compared with a shorter stay, the patient is at greater risk for infection with more resistant pathogens, and empirical treatment with broad-spectrum antimicrobial agents should be prescribed see discussion of treatment below.

Growing evidence suggests that early, appropriate antibiotic therapy improves outcomes, 2425 and such therapy should therefore acineyobacter a goal; however, this strategy needs to be coupled with an early reassessment of both diagnosis and therapy, usually within 48 to 72 hours.


In the majority of cases, the antibiotic coverage can then be reduced to a more targeted regimen based on the results of respiratory cultures or even discontinued, if an alternative diagnosis is identified. When definitive antibiotic therapy is warranted, a relatively short course 8 days should be prescribed for patients with uncomplicated ventilator-associated pneumonia acinetobbacter receive appropriate antibiotic therapy initially.

Finally, the importance of preventive measures for ventilator-associated pneumonia deserves specific mention, particularly a bundled approach Table 3. Infection of the bloodstream remains a life-threatening occurrence and is most commonly associated with the presence of a central vascular catheter but may also be associated with a gram-negative infection in other areas of the body, such as the lung, genitourinary tract, or abdomen.

Given an adequate portal of axinetobacter, almost any gram-negative organism can cause bloodstream infection; however, the most common organisms include klebsiella species, Escherichia colienter-obacter species, and P. As described above for organisms that cause hospital-acquired pneumonia, resistance is an emerging problem, particularly resistance against extended-spectrum cephalosporins and carbapenems.

For example, of bloodstream isolates of Klebsiella pneumoniae from acinetobcter throughout the United States, The most recent challenge has been the spread of carbapenemase-producing Enterobacteriaceae.

Furthermore, they often coexist with other resistance genes, including the most widespread of the ESBLs the bla CTX-M geneaminoglycoside plasmid-mediated quinolone-resistance genes qnrA and qnrB30 thus leaving the physician with few therapeutic options. As has been described for the nonfermenting gram-negative organisms, K. As with hospital-acquired pneumonia, delays in the administration of appropriate antibiotic acinetlbacter are associated with excess mortality among patients with hospital-acquired bloodstream infection, 32 although the data reflect predominantly gram-positive infections.

Data on the clinical effect of initial therapy for gram-negative bloodstream infection are more heterogeneous. Empirical antibiotic coverage for gram-negative bacteria should be considered for patients who are immunosuppressed, those in the ICU, those with a femoral catheter, those with gram-negative bacterial infection at another anatomical site particularly the lung, genitourinary tract, or abdomenand those with other risk factors for resistant organisms Table 1.

Moreover, patients who present at the hospital with suspected bloodstream infection who have health care—associated risk factors should be treated initially with broad-spectrum empirical antibiotics, pending the results of blood cultures.

Prevention of bloodstream infections associated with central catheters is of paramount importance.

Adherence to evidence-based interventions has proved highly acinetobxcter Table 335 and hospitals worldwide should be adopting such cost-effective, preventive measures. Evidence is also emerging in support of other interventions, such as the use of catheters impregnated with an antiseptic, an antibiotic, or both 36 or the use of chlorhexidine-impregnated dressings 37 ; however, when the described interventions for best practice are adhered to, the cost-effectiveness of these interventions is less clear.

Gram-negative organisms predominate in hospital-acquired urinary tract infections, almost all of which are associated with urethral catheterization. The majority of cases of bacteriuria are asymptomatic, and the most effective management is removal of the catheter rather than antibiotic treatment. In rare cases, local and systemic complications ensue, and antibiotic treatment should be initiated for asymptomatic bacteriuria in patients who are about to undergo urologic surgery or implantation of a prosthesis.

Bloodstream infection appears to be a well-defined but rare complication of catheter-associated urinary tract infection. To reduce the morbidity associated with hospital-acquired urinary tract infections and prevent the dissemination of drug-resistant gram-negative organisms, adherence acinetovacter evidence-based prevention guidelines is strongly recommended Table 3.

Until further data are available, we do not recommend the use of antibiotic-impregnated or silver-coated urinary catheters.

The importance of knowing local antimicrobial susceptibility to direct empirical antibiotic therapy cannot be overemphasized. The polymyxins colistin and polymyxin B are an older antibiotic class that has seen a resurgence of use in recent years and deserves mention. Discovered in the late s, polymyxins have specificity for lipopolysaccharides on the outer cell membrane of gram-negative bacteria. Organisms inherently resistant to polymyxins include serratia, proteus, Stenotrophomonas ainetobacterBurkholderia cepaciaand flavobacterium.

Their use was initially hampered by nephrotoxicity and then rapidly declined with the advent of newer antibiotics. However, this class of antibiotic has been reinstated as a key therapeutic option for carbapenem-resistant organisms, particularly P.

It is still a challenge acinrtobacter determine the appropriate dosage, since the polymyxins were never subjected to the rigorous drug-development process we now expect for new antimicrobial agents. Recently licensed agents with activity against gram-negative bacteria include tigecycline, which is a parenteral glycylcycline antibiotic, and doripenem, which is a parenteral carbapenem that appears to have activity similar to that of meropenem.


Tigecycline, a minocycline derivative with a broader spectrum of activity, is approved for the treatment of complicated skin, soft-tissue, and intraabdominal infections. In vitro activity of tigecycline against a range of troublesome gram-negative organisms, including ESBL-producing and carbapenemase-producing Enterobacteriaceae, acinetobacter species, and Stenotrophomonas maltophiliahas been reported P.

Clinical experience with treating these multidrug-resistant bacteria remains limited, however. The urine concentrations of tigecycline are low, so it is not suitable for the treatment of urinary tract infections.

Furthermore, it was shown to be inferior to imipenem—cilastatin for the treatment of ventilator-associated pneumonia in a randomized, double-blind trial. There is still much debate about the role of combination therapy versus monotherapy for gram-negative infections. The results of earlier studies and meta-analyses are difficult to interpret, but more recent evidence is starting to clarify this issue.

For empirical treatment, combination therapy improves the likelihood that a drug with in vitro activity against the suspected organism is being administered often defined as appropriate therapy. The antibiotics selected for the combination, however, need to be tailored to local susceptibility data, because the benefits can be lost in the presence of high cross-resistance, such as to fluoroquinolones and third-generation cephalosporins.

When the antibiotic susceptibilities of the infecting organism are known, monotherapy and combination therapy have similar outcomes, including rates of emergence of resistance and recurrence of infection. Therefore, we recommend institution-tailored combination therapy for the empirical treatment of serious hospital-acquired gram-negative infections, followed by de-escalation to monotherapy once susceptibilities have been determined.

These strategies are particularly useful for infections caused by multidrug-resistant organisms Table 5. Nebulized antibiotics such as tobramycin, amikacin, and colistimethate sodium attempt to minimize systemic toxicity and improve drug delivery at the site of infection. For severe or refractory cases of pneumonia or those caused by highly drug-resistant organisms, nebulized antibiotics given as an adjunct to systemic antibiotics should be thought of as a therapeutic option Table 5.

Hospital-Acquired Infections Due to Gram-Negative Bacteria

Respiratory toxicity such as bronchospasm has been reported and may be diminished or prevented by the administration of bronchodilators before dosing. Moreover, a recent Food and Drug Administration alert informed physicians about the importance of using aerosolized colistimethate sodium soon after preparation to prevent lung toxicity from the active colistin form. We thank Howard Gold and David Paterson for their critical review of an earlier version of the manuscript.

Acinetobxcter other conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM. National Center for Biotechnology InformationU. N Engl J Med. Author manuscript; available in PMC Jun 3. Author information Copyright and License information Disclaimer. Address reprint requests to Dr.

The publisher’s final edited version of this article is available at N Engl J Med. See other articles in PMC that cite the published article. Types of Infections Hospital-acquired infections are a major challenge to patient safety.

Open in a separate window. Mechanisms adinetobacter Resistance in Gram-Negative Bacteria, and the Antibiotics Affected Seven mechanisms of resistance are shown in acineotbacter gram-negative bacterium, with some being mediated by a mobile plasmid.

Pneumonia Hospital-acquired acinetobactrr is the most common adinetobacter hospital-acquired infection, and the majority of cases are associated with mechanical ventilation. Diagnostic criteria Presence of a new or progressive infiltrate on chest radiography and two of the following three clinical features: Bloodstream Infection Infection of the bloodstream remains a life-threatening occurrence xcinetobacter is most commonly associated with the presence of a central vascular catheter but acinetobactsr also be associated with a gram-negative infection in other areas of the body, such as the lung, genitourinary tract, or abdomen.

Urinary Tract Infection Gram-negative organisms predominate in hospital-acquired urinary tract infections, almost all of which are associated with urethral catheterization. Treatment Options The importance of knowing local antimicrobial susceptibility to direct empirical antibiotic therapy cannot be overemphasized.

These recommendations are based on the treatment of adults with normal renal function.

Colistin as for carbapenemase-producing Enterobacteriaceae For A. Footnotes No other conflict of adinetobacter relevant to this article was reported. Estimating health care-associated infections and deaths in U. Natl Vital Stat Rep.