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Acinetobacter infection: Treatment and prevention

Acinetobacter infection: Treatment and prevention
Literature review current through: Jan 2024.
This topic last updated: Nov 08, 2023.

INTRODUCTION — Acinetobacter is a gram-negative coccobacillus that has emerged from an organism of questionable pathogenicity to an infectious agent of importance to hospitals worldwide [1]. The organism has the ability to accumulate diverse mechanisms of resistance, leading to the emergence of strains that are resistant to all commercially available antibiotics [2].

Acinetobacter baumannii is one of the ESCAPE organisms, a group of clinically important, predominantly health care-associated organisms that have the potential for substantial antimicrobial resistance [3,4]. Other ESCAPE organisms are Enterococcus faecium, Staphylococcus aureus, Clostridioides difficile, Pseudomonas aeruginosa, and Enterobacteriaceae [4]. In addition, carbapenem-resistant A. baumannii is one of the critical-priority pathogens on the World Health Organization priority list of antibiotic-resistant bacteria for effective drug development [5].

A. baumannii are included in the Acinetobacter calcoaceticus baumannii complex, which also includes A. calcoaceticus, A. pittii, and A. nosocomialis. For the purposes of this document, we will use the term A. baumannii to refer to the entire A. calcoaceticus baumannii complex.

The treatment and prevention of Acinetobacter infection will be reviewed here. The clinical features, epidemiology, microbiology, and pathogenesis of Acinetobacter infection are discussed separately. (See "Acinetobacter infection: Epidemiology, microbiology, pathogenesis, clinical features, and diagnosis".)

ANTIBIOTIC RESISTANCE — Acinetobacter has the ability to develop resistance through several diverse mechanisms, which has led to emergence of strains that are resistant to all commercially available antibiotics [2].

Definitions — In 2011, a joint initiative by the European Centre for Disease Prevention and Control (ECDC) and the United States Centers for Disease Control and Prevention (CDC) proposed specific definitions for characterizing drug resistance in organisms that cause many health care-associated infections, and, in 2022, the CDC updated the definition of multidrug resistance [6,7]. For Acinetobacter, the following definitions were established based on the extent of resistance to antibiotics that would otherwise serve as treatments for Acinetobacter (table 1):

Multidrug-resistant – Isolate is nonsusceptible to at least one agent in three or more antibiotic groups (ie, third- or fourth-generation cephalosporins, fluoroquinolones, aminoglycosides, carbapenems, piperacillin-tazobactam, ampicillin-sulbactam) [7].

Extensively drug-resistant – Isolate is nonsusceptible to at least one agent in all but two or fewer antibiotic classes.

Carbapenem-resistant – Isolate is nonsusceptible to at least one antipseudomonal carbapenem.

Pandrug-resistant – Isolate is nonsusceptible to all agents.

Prior to this publication, there was no standard definition for the term "multidrug resistant," which partly accounts for the significant heterogeneity of clinical studies evaluating various regimens for drug-resistant Acinetobacter infections.

Epidemiology and risk factors

Epidemiology of resistant strains – Globally, resistant strains have become increasingly common causes of nosocomial infections since the 1980s [8-29]. In a 2009 report of surveillance data from more than 100 centers worldwide, 61 percent of Acinetobacter isolates were resistant to ceftazidime and 67 percent were resistant to ciprofloxacin [30]. These results are significantly worse than those published in 2007 from the same reporting system (34 and 40 percent resistance, respectively) [9]. Carbapenem and tobramycin resistance increased as well (from 10 percent to 54 percent for carbapenems, and 8 to 41 percent for tobramycin).

A more recent global analysis of over 4300 A. baumannii isolates identified between 2016 and 2018 found significant regional variation in rates of resistance [31]. Overall global resistance to meropenem was 67 percent, with the highest rate (83 percent) in the Africa/Middle East region. Similar variation was noted for levofloxacin and amikacin, for which global resistance rates were 71 and 57 percent, respectively, with the highest resistance rates for levofloxacin found in Africa/Middle East (85 percent) and in Latin America for amikacin (72 percent). North America was the only region with resistance rates below 50 percent for meropenem (36 percent), levofloxacin (45 percent), and amikacin (22 percent). Colistin resistance was below 7 percent in all regions of the world.

In the United States, the emergence of resistance among Acinetobacter strains has also been demonstrated by analysis of The Surveillance Network, an electronic passive surveillance database that collects information from clinical laboratories across the United States [32]. Multidrug resistance, defined as nonsusceptibility to at least one agent in three or more antibiotic groups (excluding fluoroquinolones), increased from 21 percent during 2003 to 2005 to 35 percent during 2009 to 2012 [33]. Resistance to carbapenems more than doubled during this time, from 21 to 48 percent.

The rising prevalence of antimicrobial resistance among A. baumannii isolates has influenced the epidemiology of serious hospital-acquired infections. In a systematic review, carbapenem-resistant and multidrug-resistant A. baumannii accounted for 65 and 59 percent, respectively, of all hospital-acquired infections among intensive care unit patients in Southeast Asia [34]. In some countries in the Arab League, multidrug-resistant A. baumannii is the most common cause of ventilator-associated pneumonia [35].

Risk factors – Independent risk factors for colonization or infection with resistant strains of Acinetobacter include the following [16,36-40]:

Prior colonization with methicillin-resistant S. aureus (MRSA)

Prior beta-lactam use, particularly carbapenems

Prior fluoroquinolone use

Bedridden status

Current or prior intensive care unit admission

Presence of a central venous catheter

Recent surgery

Mechanical ventilation

Hemodialysis

Malignancy

Glucocorticoid therapy

Mechanisms of resistance — Acinetobacter species are capable of accumulating multiple antibiotic resistance genes, leading to the development of multidrug-resistant or extensively drug-resistant strains [41,42]. Frequently expressed resistance mechanisms in nosocomial strains of Acinetobacter include beta-lactamases, alterations in cell wall channels (porins), and efflux pumps:

AmpC beta-lactamases are chromosomally encoded cephalosporinases intrinsic to all A. baumannii. Usually, such beta-lactamases have a low level of expression that does not cause clinically appreciable resistance; however, the addition of a promoter insertion sequence ISAba1 next to the AmpC gene increases beta-lactamase production, causing resistance to cephalosporins [43].

The most troubling clinical resistance mechanism has been the acquisition of beta-lactamases in Acinetobacter, including serine and metallo-beta-lactamases, which confer resistance to carbapenems [44]. Acquired extended-spectrum beta-lactamase carriage occurs in Acinetobacter but is not as widespread as in Klebsiella pneumoniae or Escherichia coli [45]. (See "Extended-spectrum beta-lactamases" and "Carbapenem-resistant E. coli, K. pneumoniae, and other Enterobacterales (CRE)".)

Porin channels in A. baumannii are poorly characterized; it is known that reduced expression or mutations of bacterial porin proteins can hinder passage of beta-lactam antibiotics into the periplasmic space, leading to antibiotic resistance.

Overexpression of bacterial efflux pumps can decrease the concentration of beta-lactam antibiotics in the periplasmic space. To cause clinical resistance in Acinetobacter, efflux pumps usually act in association with overexpression of AmpC beta-lactamases or carbapenemases. Efflux pumps can remove beta-lactam antibiotics as well as quinolones, tetracyclines, chloramphenicol, and tigecycline [46].

A. baumannii can become resistant to quinolones through mutations in the genes gyrA and parC and can become resistant to aminoglycosides by expressing aminoglycoside-modifying enzymes [44].

The mechanism of resistance of Acinetobacter to colistin appears to be associated with a mutation in the genes encoding the PmrA and B proteins; additional regulatory factors remain to be determined [47].

Heteroresistance, characterized by resistant subpopulations within a single strain, has been described in Acinetobacter strains [48]. (See "Overview of antibacterial susceptibility testing", section on 'Heteroresistance'.)

CONSIDERATIONS PRIOR TO SELECTING AN ANTIBIOTIC REGIMEN

Differentiating colonization from infection — Acinetobacter can be readily identified on culture of relevant clinical specimens. However, differentiating colonization from true infection can be challenging and depends on the anatomic site from which the culture sample was obtained and the patient's clinical presentation.

Cultures from sterile sites – Growth of the organism from normally sterile sites (eg, blood, pleural fluid, peritoneal fluid, cerebrospinal fluid) should be interpreted as representing true infection.

Cultures from nonsterile sitesAcinetobacter frequently causes colonization, especially among patients with prolonged hospitalizations. (See 'Epidemiology and risk factors' above.)

Clinical evaluation of the patient is necessary to determine whether a positive culture from a nonsterile site represents true infection. Colonization should not be treated, because inappropriate antibiotic use contributes to added adverse effects and selects for resistant organisms.

Patients with clinical evidence of pneumonia (eg, new pulmonary infiltrate, decreased oxygenation, and fever and/or leukocytosis) whose respiratory culture grows Acinetobacter should be considered to have true infection. In the absence of consolidation on chest radiography and other clinical signs of pulmonary infection, respiratory growth of Acinetobacter probably represents colonization rather than invasive disease.

Asymptomatic bacteruria should not be treated in most individuals, including those with urinary catheters. Further discussion can be found elsewhere. (See "Asymptomatic bacteriuria in adults".)

Cultures from other nonsterile sites, such as wounds, should also undergo clinical scrutiny. In the absence of clinical evidence of infection, such as fever, leukocytosis, or localized inflammation or purulence, the culture findings may be presumed to reflect colonization rather than infection.

Indications for empiric therapy — In select cases, we suggest empiric treatment for possible Acinetobacter infection. Primarily, we provide empiric therapy to patients with moderate to severe infection (eg, ventilator-associated pneumonia, urosepsis) who have had prior cultures at the site of infection that grew Acinetobacter. In such cases, a combination of antibiotics should be chosen that were active against the prior isolates. If the organism ultimately grows from culture, we alter our regimen once susceptibility results return, as described below. (See 'Suggested antibiotic regimens' below.)

Determining the likelihood of resistance — The likelihood of resistance should be assessed prior to selecting empiric antibiotics to treat Acinetobacter infections. Factors that can predict resistance include the following:

The patient's prior culture results – Patients with prior cultures that grew multidrug-resistant Acinetobacter are likely to have ongoing resistance. For such patients, empiric antibiotic selection should include agents effective against the prior isolates.

The patient's prior antibiotic exposure – Patients who have received broad-spectrum antibiotics prior to developing an Acinetobacter infection have an increased likelihood of resistance to those antibiotics. In these situations, antibiotics from a different class should be chosen for empiric therapy.

Local resistance rates – Elevated local rates of resistance of Acinetobacter isolates may predict resistance in individual patients. If local resistance rates to beta-lactams, carbapenems, fluoroquinolones, and aminoglycosides are higher than 10 to 15 percent, a highly resistant pathogen should be suspected, and empiric therapy should be altered accordingly.

Severity of infection — When making treatment decisions, we generally divide Acinetobacter infections into one of two categories: mild versus moderate to severe. Clinical judgment is of paramount importance when making these distinctions.

Mild infections – In the absence of severe sepsis or septic shock, we generally categorize urinary tract infections (UTIs) and skin and soft tissue infections as mild as long as source control is achieved (eg, removal of urinary catheter, debridement of infected soft tissue), if applicable. Select cases of pneumonia may be categorized as mild if no systemic symptoms (eg, fever >100.5°F/38°C, tachycardia, tachypnea), hypoxia, mechanical ventilation, or other concerning features are present; some providers may label this syndrome as "tracheitis" as opposed to pneumonia.

Moderate to severe infections – Moderate to severe infections include any infection for which heightened clinical concern is present or the criteria for mild infection are not met. Examples include severe sepsis or septic shock; infections for which source control has not been achieved (eg, foreign material is retained, abscess is not drained); or any infection other than UTI, skin and soft tissue infection, or mild pneumonia.

SUGGESTED ANTIBIOTIC REGIMENS — Antibiotic options for treatment of Acinetobacter are limited due to high rates of resistance. (See 'Antibiotic resistance' above.)

Our suggested antibiotics are divided into two groups: first-line antibiotics and second-line antibiotics. In general, first-line antibiotics are preferred for susceptible isolates and include beta-lactam antibiotics, carbapenems, and fluoroquinolones (as well as aminoglycosides for urinary tract infections [UTIs]). Second-line agents include polymyxins (ie, polymyxin B and colistin) and tetracycline derivatives (eg, minocycline and tigecycline) and are reserved for resistant isolates. Details regarding specific antibiotics are discussed below. (See 'Antibiotic efficacy and safety' below.)

Prior to selecting an antibiotic regimen, certain factors should be considered including the likelihood of resistance and indications for empiric therapy, as described above (see 'Indications for empiric therapy' above and 'Determining the likelihood of resistance' above). Additionally, the anatomic site of infection (eg, pneumonia, bacteremia, meningitis, osteomyelitis) may alter antibiotic selection and is discussed below. (See 'Disease-specific considerations' below.)

Our suggested regimens depend primarily on severity of illness, as defined above (see 'Severity of infection' above). Other considerations include patient drug allergies or intolerances, need to cover additional infections, and hospital formulary. In general, our approach is consistent with those of expert guidelines [49,50].

Detailed regimens are outlined in the algorithm (algorithm 1) and dosing recommendations are listed in the table (table 2).

Mild infections — For mild infection, we typically suggest monotherapy based on the results of the isolate's antibiotic susceptibility testing. An active first-line agent (ie, a beta-lactam antibiotic, carbapenem, or fluoroquinolone) is preferred over a second-line agent (a polymyxin or tetracycline derivative). An aminoglycoside or trimethoprim-sulfamethoxazole can be used as monotherapy for susceptible UTIs. For simple cystitis, some experts try fosfomycin although its efficacy is debatable. Regimens, doses, and supportive data are outlined in the algorithm (algorithm 1), table (table 2), and elsewhere. (See 'Antibiotic efficacy and safety' below.)

If susceptibility results are not yet available or empiric therapy is indicated, the likelihood of resistance should determine the regimen selection (see 'Determining the likelihood of resistance' above). If resistance is unlikely, we suggest monotherapy with a first-line agent. If resistance is likely, we suggest treating with combination therapy using our suggested regimen for empiric therapy of moderate to severe infections, as described below (see 'Moderate to severe infections' below). Once results of antimicrobial susceptibility are available, a regimen can be chosen from among the active agents.

Moderate to severe infections — We suggest initial combination therapy for all moderate to severe infections, and the choice of agents is based on the results of the isolate's antibiotic susceptibility testing.

Isolates for which susceptibility results are available – Detailed regimen selections and doses are seen in the algorithm (algorithm 1) and table (table 2).

Isolates susceptible to one or more first-line agents – For isolates susceptible to more than one first-line agent, we combine two active first-line agents from different classes (ie, a beta-lactam antibiotic or carbapenem with either a fluoroquinolone or aminoglycoside, or a fluoroquinolone with an aminoglycoside).

Sulbactam-durlobactam is a newer first-line beta-lactamase inhibitor antibiotic combination that should be reserved for use only in patients with A. baumannii hospital-acquired or ventilator-associated pneumonia or bacteremia whose isolate is resistant to other first-line agents, as discussed below. (See 'First-line antibiotics' below.)

For isolates susceptible to only one first-line agent, we combine the active first-line agent with a second-line agent to which the isolate is susceptible. To prevent additive adverse effects, we avoid combining beta-lactam antibiotics with carbapenems. We also avoid combining polymyxins with carbapenems (unless a third agent is added) because data suggest lack of benefit of this combination compared with colistin monotherapy [51].

Isolates resistant to all first-line agents – For isolates resistant to all first-line agents, we favor combining two active second-line agents (ie, a polymyxin and a tetracycline derivative [either minocycline or tigecycline]), if possible.

For isolates susceptible to only a tetracycline derivative and an aminoglycoside, we combine those two agents.

For isolates only susceptible to one second-line agent or an aminoglycoside, we generally favor triple therapy that includes the one active agent with two agents to which the isolate is resistant. Specifically, we combine the only active agent (ie, the active polymyxin, tetracycline derivative, or aminoglycoside) with high-dose extended-infusion ampicillin-sulbactam and high-dose extended-infusion meropenem. For isolates susceptible to cefiderocol in these situations, some experts may replace the meropenem with cefiderocol, although data supporting its use are lacking. Some experts may consider replacing the ampicillin-sulbactam with sulbactam-durlobactam. We avoid the combination of a polymyxin and an aminoglycoside, unless there are no other options, due to increased risk of renal toxicity.

For isolates resistant to all antibiotics, data are extremely limited, and the optimal approach is uncertain. In such cases, we often administer triple therapy with high-dose extended-infusion ampicillin-sulbactam plus two of the following: a high-dose extended infusion of meropenem, a polymyxin, or a tetracycline derivative. If cefiderocol is the only active agent, some experts would include it in the regimen. Some experts may consider replacing the ampicillin-sulbactam with sulbactam-durlobactam. Outcomes with these regimens are uncertain.

Consultation with an expert is advised for these infections.

Isolates for which empiric therapy is indicated or susceptibility results are pending – For these, we generally combine either ampicillin-sulbactam or a carbapenem with a first- or second-line agent, depending on the suspected susceptibility profile of the isolate. Due to data suggesting a lack of benefit, we avoid combining polymyxins with carbapenems (unless a third agent is added) [51]. Once results of antimicrobial susceptibility results are available, a regimen can be chosen from among the active agents (table 2).

The rationale for combination therapy is discussed below. (See 'Role of combination antibiotic therapy' below.)

For most infections, we transition combination therapy to monotherapy once clinical improvement occurs. However, for primary bloodstream infections, severe pneumonia, and severe intra-abdominal infections, we continue combination therapy for the full course of therapy.

ANTIBIOTIC EFFICACY AND SAFETY — Inherent and acquired resistance limits the number of antimicrobial options for Acinetobacter. Very few trials have evaluated the efficacy and safety of different antimicrobial regimens for Acinetobacter infections, and most available data for Acinetobacter infections are derived from in vitro studies and observational series. Most of these studies, however, are limited by their small sample sizes, variability in the severity of disease and comorbidities in the included patients, and the lack of a comparator group.

First-line antibiotics — Infections caused by antibiotic-susceptible Acinetobacter isolates may have several first-line therapeutic options, including broad-spectrum cephalosporins (ceftazidime or cefepime), piperacillin-tazobactam, ampicillin-sulbactam, carbapenems (eg, meropenem or imipenem-cilastatin), and fluoroquinolones (eg, ciprofloxacin). Aminoglycosides and trimethoprim-sulfamethoxazole are also acceptable first-line agents for infections isolated to the urinary tract.

We often use one of these agents for monotherapy or as part of combination therapy depending on the severity of illness. Specific antibiotic regimens are discussed above and in the algorithm (algorithm 1 and table 2). (See 'Suggested antibiotic regimens' above.)

Beta-lactam antibiotics – Five beta-lactam antibiotics often have activity against Acinetobacter: ceftazidime, cefepime, piperacillin-tazobactam, ampicillin-sulbactam, and sulbactam-durlobactam.

There are no data comparing these agents to each other, so one agent is not preferred over the others. However, ampicillin-sulbactam and sulbactam-durlobactam sometimes retain activity against multidrug-resistant isolates, so we typically reserve them for infections resistant to other first-line agents.

Ampicillin-sulbactam – This antibiotic is unique because the sulbactam component (a beta-lactam with beta-lactamase inhibitor activity) of the combination drug has excellent stand-alone bactericidal activity against Acinetobacter even in the absence of ampicillin. The unique mechanism of action of sulbactam can preserve its activity when resistance to other beta-lactam antibiotics and carbapenems is present [52,53]. In the United States and many other countries, sulbactam is available only in combination with ampicillin [54-56].

Dosing recommendations for ampicillin-sulbactam vary among experts. For highly resistant Acinetobacter infections, some published reports used higher doses than typically recommended by the manufacturer [57-59]. Our dosing suggestions, which are based on severity of illness, can be found in the table (table 2) and generally match those of published guidelines [49,50].

Limited retrospective studies comparing ampicillin-sulbactam to other active agents (eg, imipenem, a polymyxin) as monotherapy or part of combination therapy for treatment of Acinetobacter infections suggest that ampicillin-sulbactam is at least as effective as alternative agents. In the studies, clinical success rates for ampicillin-sulbactam ranged from 83 to 93 percent [54,55,60,61].

For carbapenem-resistant Acinetobacter infections, two meta-analyses have evaluated various treatment regimens. One meta-analysis of 18 studies and over 1800 patients found that combination therapy that included ampicillin-sulbactam (with daily doses of at least 18 g per day) reduced mortality and had less nephrotoxicity in critically ill patients compared with colistin-based regimens [62]. Another meta-analysis of 23 studies and over 2100 patients found that sulbactam-containing regimens reduced mortality compared with polymyxin-based or tigecycline-based regimens [63].

For moderate to severe infections with extensive drug resistance, we sometimes use high-dose prolonged-infusion ampicillin-sulbactam in combination regimens even if the isolate is reported as resistant. The rationale for this practice is based on pharmacokinetics that suggest that high doses of sulbactam can overcome the molecular mechanisms of resistance [57,64]. Limited clinical data support this approach for Acinetobacter infections, so it is reserved for infections for which very few active antibiotics are available. More information regarding prolonged infusions can be found elsewhere. (See "Prolonged infusions of beta-lactam antibiotics".)

Sulbactam-durlobactam – Sulbactam-durlobactam is a newer beta-lactam/beta-lactamase inhibitor combination that was developed specifically to treat Acinetobacter spp. In vitro, it is highly active against A. baumannii, exhibiting a 32-fold reduction in MIC90 compared with sulbactam alone [65]. In 2023, based on clinical data, it was approved by the United States Food and Drug Administration (FDA) for the treatment of hospital-acquired and ventilator-associated pneumonia (HAP and VAP, respectively) due to carbapenem-resistant strains of A. baumannii that are susceptible to sulbactam-durlobactam.

The primary study used for FDA approval of sulbactam-durlobactam was a randomized trial conducted at 59 clinical sites in 16 countries from 2019 to 2021 [66]. A total of 125 patients with infection due to carbapenem-resistant A. baumannii (122 with HAP or VAP, and 3 with bacteremia) were randomized to imipenem-cilastatin plus either sulbactam-durlobactam or colistin and were followed for 28 days. Twelve of 63 patients (19 percent) in the sulbactam-durlobactam group died within 28 days from any cause, compared with 20 of 62 (32 percent) in the colistin group (difference -13.2percent; 95% CI -30.0 to 3.5 percent). The rate of clinical cure was 62 percent in the sulbactam-durlobactam group compared with 40 percent in the colistin group (difference 22 percent; 95% CI 2.9 to 40.3 percent), and rate of microbiologic eradication of the organism at the end of therapy was 86 percent in the sulbactam-durlobactam group compared with 61 percent in the colistin group (difference 24 percent; 95% CI 7.9 to 40.9 percent). Nephrotoxicity was lower in the sulbactam-durlobactam group compared with the colistin group (12 versus 32 percent, respectively).

Because of its activity against highly-resistant isolates and limited clinical data, we reserve this agent for patients with A. baumannii hospital-acquired or ventilator-associated pneumonia or bacteremia whose isolate is resistant to other first-line agents.

Other first-line agentsCeftazidime, cefepime, and piperacillin-tazobactam have less data to support their use, but they have been used extensively in clinical practice. We routinely use them to treat infections caused by susceptible isolates.

The adverse effects of beta-lactams are discussed in detail elsewhere. (See "Beta-lactam antibiotics: Mechanisms of action and resistance and adverse effects", section on 'Adverse effects'.)

Carbapenems – Certain carbapenems (ie, meropenem, imipenem) are highly bactericidal against susceptible strains of Acinetobacter [52].

Because isolates that are susceptible to imipenem may be resistant to meropenem and vice versa, susceptibility to specific carbapenems should be confirmed prior to use [67,68]. Ertapenem has little intrinsic activity against Acinetobacter and should not be used [69-71].

The clinical cure rates with imipenem for ventilator-associated pneumonia due to Acinetobacter range from 57 to 83 percent in small series [46-48,60]. For bacteremia, one small case series reported successful clinical outcome in 56 percent of individuals treated with imipenem [55].

For severe infections or infections with elevated minimum inhibitory concentrations (MICs) for meropenem (ie, MIC of 4 or 8 mcg/mL), higher doses and prolonged infusions of meropenem are often used to improve pharmacodynamics by increasing the time above MIC. Limited clinical data support this approach for Acinetobacter infections, so it is reserved for infections for which very few active antibiotics are available [72-74]. More information regarding prolonged infusions can be found elsewhere. (See "Prolonged infusions of beta-lactam antibiotics".)

FluoroquinolonesAcinetobacter isolates are sometimes susceptible to one or more fluoroquinolones (eg, ciprofloxacin, levofloxacin) [75,76]. A benefit of the fluoroquinolones is that they are available in both oral and parenteral formulations. Data are limited regarding their use for treatment of Acinetobacter infections, but they are commonly used to treat susceptible isolates. Susceptibility breakpoints are available only for ciprofloxacin and levofloxacin [77,78]. (See 'Suggested antibiotic regimens' above.)

Aminoglycosides – Aminoglycosides (eg, gentamicin, tobramycin, amikacin) often exhibit in vitro activity against Acinetobacter [79,80]. These antibiotics are first-line agents as monotherapy for urinary tract infections (UTIs) without associated bacteremia because they achieve high urine concentrations. However, outside the urinary tract, data are limited, and we suggest not using them unless they are used as part of a combination regimen.

Trimethoprim-sulfamethoxazole – This agent is an option for UTIs, although most Acinetobacter isolates are resistant [81]. We use trimethoprim-sulfamethoxazole for treatment of UTIs without severe sepsis or bacteremia and only if the urine isolate is reported to be susceptible. Due to lack of clinical data, we do not use it as part of combination regimens. Further details regarding use of trimethoprim-sulfamethoxazole for UTIs are found elsewhere. (See "Acute simple cystitis in adult and adolescent females", section on 'Directed antimicrobial selection' and "Acute complicated urinary tract infection (including pyelonephritis) in adults and adolescents", section on 'Regimen selection'.)

Emergence of resistance to first-line agents during therapy has been observed, especially when used as single agents [10,82]. For this reason, these agents are sometimes used in combination for serious infections, as described below [67,68]. (See 'Role of combination antibiotic therapy' below.)

Second-line antibiotics — In the setting of resistance to the first-line agents, therapeutic options are limited. Polymyxins (ie, polymyxin B and colistin) and certain tetracycline derivatives (ie, minocycline and tigecycline) are the main therapeutic options for extensively drug-resistant Acinetobacter.

We consider polymyxins to be second-line agents because of their adverse effects and complex dosing. Tetracycline-based antibiotics have less concerning adverse effects but have limited distribution in certain tissues. In general, clinical experience with both classes of antibiotics is less than with beta-lactam antibiotics and fluoroquinolones.

Dosing is summarized in the table (table 2). We sometimes use one of these agents for monotherapy or as part of combination therapy depending on the severity of illness and susceptibility profile of the isolate.

Specific regimens and suggested doses are summarized above and in the algorithm (algorithm 1) and table (table 2). (See 'Suggested antibiotic regimens' above.)

Polymyxins – Polymyxins (polymyxin B and colistin [polymyxin E]) are commonly used for Acinetobacter isolates resistant to first-line agents.

The dose for polymyxin B and colistin depends on the formulation available, which varies by geographic region. In addition to variable dosing algorithms based on formulation, serum levels can vary among individuals treated with the same agent following the same dosing algorithm. Expert panels recommend drug level monitoring during treatment, although these tests are not universally available [83]. Details regarding dosing of polymyxins are discussed elsewhere. (See "Polymyxins: An overview", section on 'Intravenous administration'.)

Clinical data comparing polymyxin B to colistin are limited. In general, for infections outside the urinary tract and lung, polymyxin B is favored because pharmacokinetic studies suggest that it achieves adequate drug levels more rapidly and reliably than colistin [83]. For infections limited to the urinary tract, colistin is generally preferred because it converts to its active form and reaches high concentrations in the urinary tract. For pneumonia, neither agent is recommended as parenteral monotherapy due to low drug concentrations in the lung [84,85]. Often, in clinical practice, only one of the two agents is available, so they are sometimes used interchangeably. Further details regarding when we use these agents are found elsewhere. (See 'Suggested antibiotic regimens' above.)

Susceptibility breakpoints for the polymyxins differ among guidelines from the United States and Europe. Most evidence suggests that MICs >2 mcg/mL reduce the antimicrobial effect of polymyxins [86]. More details regarding susceptibility breakpoints are found elsewhere. (See "Polymyxins: An overview", section on 'Susceptibility testing'.)

Although polymyxins usually have in vitro activity against Acinetobacter [87,88], resistance has been observed, including emergence of resistance while on therapy [86,89,90]. Resistance rates of 2.7 percent in Europe and 1.7 percent in North and Latin America have been reported [89]. In the United States, colistin resistance was 6.9 percent during 2009 to 2012 [33]. Heteroresistance, in which there is a resistant subpopulation detected within an otherwise susceptible population, has also been observed [91].

There are no randomized trials addressing the efficacy of polymyxins for treatment of Acinetobacter infections. Some observational studies suggest that outcomes with polymyxins may be similar to other regimens [92-94]. In a meta-analysis of six studies of 359 patients with ventilator-associated pneumonia due mainly to A. baumannii but also P. aeruginosa, clinical outcomes with intravenous colistin were similar to those observed with a carbapenem or high-dose ampicillin-sulbactam [94]. The overall clinical response rate for colistin was 66 percent.

Nephrotoxicity is the most concerning adverse effect associated with systemic colistin and has been reported in up to 36 percent of patients [95], although, in the meta-analysis above, intravenous colistin use was not associated with excess renal dysfunction compared with the other agents evaluated [94]. Colistin dosing depends on the available preparation and should be adjusted in patients with impaired renal function. Polymyxin B is associated with lower rates of nephrotoxicity than colistin and does not need to be dose adjusted for renal function. Neurotoxicity, primarily paresthesias, is another important side effect and is relatively uncommon. (See "Polymyxins: An overview", section on 'Adverse reactions'.)

Tetracycline derivatives – Antibiotics within the tetracycline class (eg, minocycline, doxycycline, tigecycline) often have activity against Acinetobacter [96-98].

In general, we use these agents as monotherapy only for mild skin and soft tissue infections or mild pneumonia. We favor combination therapy for all other sites of infection and for more severe infections. The tetracycline class is avoided as monotherapy for urinary tract infections and bacteremia because they rapidly enter tissues following administration, which results in low urine and serum levels [52]. Further details regarding when we use these agents are found above and in the algorithm and table (algorithm 1 and table 2). (See 'Suggested antibiotic regimens' above.)

There are no data comparing these agents to each other.

Minocycline – Many resistant strains of A. baumannii are susceptible in vitro to minocycline, which can be given intravenously or orally [99].

In vitro susceptibility to minocycline can be inferred from susceptibility to tetracycline. In addition, some tetracycline-resistant strains remain susceptible to minocycline, so it is worthwhile to ask the microbiology laboratory to determine susceptibility to minocycline for tetracycline-resistant isolates. Among nearly 5500 A. baumannii strains collected from medical centers worldwide from 2007 to 2011, 79 percent were susceptible to minocycline compared with 30 and 60 percent to tetracycline and doxycycline, respectively [99].

Limited clinical experience suggests favorable outcomes with minocycline, as monotherapy or in combination [100]. In a review of retrospective case series in which minocycline was used for multidrug-resistant A. baumannii infections (predominantly ventilator-associated pneumonia), successful clinical and microbiologic outcomes were reported for most patients [101]. As an example, in a retrospective study of patients with ventilator-associated carbapenem-resistant A. baumannii pneumonia, the clinical response rate was 80 percent among the 19 who were treated with minocycline as monotherapy or as part of a combination regimen [102].

Overall, both intravenous and oral minocycline are well-tolerated, but, like other agents in the tetracycline class, they can cause photosensitivity and gastrointestinal side effects [101]. (See "Tetracyclines", section on 'Adverse reactions'.)

Doxycycline – This agent may be more available than the other tetracycline derivatives in some hospitals and pharmacies. However, less clinical data are available to support doxycycline compared with minocycline and tigecycline [103]. Studies suggest that susceptibility of A. baumannii to doxycycline is above 50 percent, at least in some locales. For example, among 93 isolates from a hospital in India, 64 (69 percent) were susceptible [104].

However, in a study of over 5400 isolates of A. baumannii collected from hospitals around the world, minocycline was estimated to be two-fold more potent than doxycycline [99]. Susceptibility rates were also lower for doxycycline (60 percent) than for minocycline (79 percent).

Tigecycline – Tigecycline has activity against some multidrug- and extensively resistant strains of A. baumannii, although clinical experience is limited [46,53,89,105-111]. Tigecycline is only available in parenteral formulation.

Unlike minocycline and doxycycline, susceptibility breakpoints for tigecycline are not available for Acinetobacter isolates. Furthermore, in vitro susceptibility to tigecycline cannot be inferred from susceptibility to tetracycline or any other tetracyclines. We generally consider isolates with an MIC ≤0.5 mg/L to be susceptible and isolates with MICs >0.5 mg/L to be resistant, based on European standards for Enterobacterales [77].

We use different dosages of tigecycline depending on the clinical syndrome and severity of illness (table 2). A retrospective study suggested that tigecycline was well tolerated at higher than standard doses in critically ill patients with multidrug-resistant gram-negative infections, including Acinetobacter [112]. The higher dose was associated with better outcomes than standard dosing, particularly among those with ventilator-associated pneumonia, a finding that has been replicated in other studies as well [113-116].

Clinical data regarding the use of tigecycline to treat Acinetobacter infections suggest that tigecycline may provide comparable outcomes compared with other regimens. A meta-analysis of 24 studies found no differences in all-cause mortality and clinical response with tigecycline versus comparators, but tigecycline was associated with a lower microbial eradication rate and a trend for longer hospitalization [117]. Overall, studies of tigecycline for Acinetobacter infections report clinical success rates of 47 to 81 percent [118-120].

Emergence of tigecycline resistance while on therapy has been reported in Acinetobacter infections, with an occurrence rate of 12 percent in the aforementioned meta-analysis [52,102,113,114,117].

Other tetracycline-based agents – Although other broad-spectrum tetracyclines (eg, eravacycline, omadacycline) have some activity in vitro against resistant A. baumannii, we do not routinely use them because clinical experience is extremely limited [121-126]. We also do not use tetracycline because susceptibility breakpoints are not available, and the rate of resistance is higher than with the tetracycline derivatives [99].

Other antibiotics

Cefiderocol – We only use cefiderocol when other effective antibiotics are not an option, and we only use it as part of a combination regimen. Although most isolates of extensively resistant A. baumannii remain susceptible to cefiderocol (including those possessing OXA-type beta-lactamases), clinical experience is extremely limited [127,128]. Furthermore, a randomized trial comparing cefiderocol to best-available therapy for carbapenem-resistant gram-negative infections (including 54 patients with A. baumannii infections) found a trend toward higher all-cause mortality with cefiderocol (34 versus 18 percent), although clinical cure rates were comparable [129]. The mortality difference was more pronounced among patients with Acinetobacter spp infections (50 versus 18 percent).

Emerging agents – New antimicrobials targeting multidrug-resistant A. baumannii are under development; certain agents are available in some countries, although clinical data informing their use for A. baumannii remain very limited [130]. Phage therapy has been promising as a novel therapeutic approach, but clinical data are limited to a few case reports [131,132].

Antibiotics that are not effective — In general, fosfomycin and aztreonam should not be used because Acinetobacter is usually intrinsically resistant to both agents [49,50,133-137]. For simple cystitis in the absence of systemic symptoms, some experts administer a trial of oral fosfomycin; however, there are no standardized breakpoints to determine susceptibility, and the United States Clinical and Laboratory Standards Institute expert panel on antibiotic resistance considers A. baumannii to be intrinsically resistant to fosfomycin [134]. Studies also suggest that rapid emergence of resistance can develop in patients on fosfomycin therapy [133].

Rifamycins (eg, rifampin, rifabutin) have activity, both in vitro and in animal studies, against Acinetobacter. However, benefit has not been proven in clinical studies. Three small trials compared monotherapy with colistin to combination colistin plus rifampin, and none found a benefit with the addition of rifampin [138-140]. Rifamycins have associated toxicities and numerous drug interactions. At this time, based on available data, we suggest not using rifamycins for monotherapy or as part of combination regimens, and our approach aligns with expert guidelines [49,50].

Novel antibiotics that should not be used because they have limited in vitro activity against Acinetobacter include ceftolozane-tazobactam and plazomicin. Furthermore, ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam should not be used because the addition of novel beta-lactamase inhibitors (avibactam, vaborbactam, and relebactam) does not confer additional activity beyond that of the primary agents (ceftazidime, meropenem, and imipenem).

Role of combination antibiotic therapy — Combination therapy is often used to treat Acinetobacter and other multidrug-resistant pathogens. We suggest it for moderate to severe infections or if multidrug resistance is suspected, as discussed elsewhere. (See 'Suggested antibiotic regimens' above.)

There are no definitive clinical data that demonstrate improved outcomes with combination versus monotherapy. However, for highly resistant Acinetobacter infections, limited available data suggest that combination therapy may be associated with improved outcomes [139,141-143].

In a retrospective study of over 300 adults with Acinetobacter ventilator-associated pneumonia, combination therapy (as opposed to monotherapy) was independently associated with lower 30-day mortality [141]. Among those with imipenem-resistant infections, 30-day mortality rates were lower with combination therapy than with monotherapy (52 versus 67 percent).

In another retrospective study that included 83 critically ill patients with extensively resistant Acinetobacter infections, therapy with polymyxin B plus another agent was associated with a lower 30-day mortality rate than with polymyxin B monotherapy (42 versus 68 percent) [142].

For empiric therapy, combination regimens are frequently used to increase the odds that at least one antibiotic will be active against the isolate. While there are no clear clinical data to support this practice for Acinetobacter infections, studies in patients with sepsis due to various pathogens have found that delayed initiation of an antibiotic to which the pathogen is susceptible leads to worse outcomes [144-149]. Further information about the importance of appropriate and timely antibiotic therapy is found elsewhere. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Timing'.)

Combination therapy is also sometimes used to decrease the risk of emergence of resistance while on therapy. Very few studies have been performed to evaluate this issue for Acinetobacter [150]. In a meta-analysis of eight trials that compared combination beta-lactam and aminoglycoside therapy with beta-lactam monotherapy for the treatment of infections caused by various organisms, combination therapy did not decrease the rate of emergent resistance (odds ratio 0.9, 95% CI 0.56-1.47) [151]. Among Acinetobacter infections specifically, there was no difference in the development of resistance between combination regimens and monotherapy (0 of 11 versus 1 of 22 infections, respectively).

MONITORING FOR EMERGENT RESISTANCE — Because of the possibility of emergence of resistance during therapy, continued monitoring of the patient is important. If there is lack of expected improvement or a decline following an initial improvement, repeat cultures to evaluate for growth of resistant Acinetobacter isolates is warranted. While awaiting culture results, therapy can be changed to different agents, preferably from different classes, if clinically indicated.

DISEASE-SPECIFIC CONSIDERATIONS

Pneumonia — The management of pneumonia caused by Acinetobacter is the same as that for Acinetobacter infections in general, as described above (see 'Suggested antibiotic regimens' above). Additional considerations include the possible use of adjunctive inhaled antibiotics.

In select patients, inhaled colistin may be beneficial when combined with a systemic antibiotic [94,152-154], although not all studies suggest a benefit [155]. Because intravenous colistin yields low lung concentrations, we favor adding inhaled colistin for patients with serious pneumonia being treated with parenteral colistin. If other options are available, we avoid the use of polymyxins for pneumonia, whether intravenous or inhaled.

The optimal dose of inhaled colistin is uncertain. Our suggested doses match those in expert guidelines and can be seen in the table (table 2) [83,156].

Among three studies evaluating inhaled colistin as adjunctive therapy to intravenous antibiotics for ventilator-associated pneumonia with drug-resistant gram-negative bacilli, predominantly A. baumannii, the pooled response rate was 80 percent [94]. The main adverse effect of inhaled colistin is bronchoconstriction [95].

Although there are reports of successful treatment of multidrug-resistant respiratory infections by combining inhaled and systemic polymyxin B [157], we do not typically use inhaled polymyxin B because of the risk of bronchospasm. (See "Polymyxins: An overview", section on 'Inhaled administration'.)

The duration of therapy is similar to that for other causes of pneumonia and is discussed separately. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Duration of therapy' and "Treatment of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Duration'.)

Bloodstream infection — The management of bacteremia is typically the same as that for Acinetobacter infections in general.

Patients with primary bacteremia are typically maintained on combination therapy for the complete treatment course. For patients being transitioned from combination therapy to monotherapy (eg, patients whose bacteremia was secondary to urinary tract infection [UTI] or another nonsevere infection), we avoid minocycline or tigecycline as monotherapy; both agents have low blood levels because they rapidly enter tissues following administration.

If bacteremia is associated with an intravascular catheter, the device should be removed [158].

The duration of therapy for uncomplicated bacteremia is similar to bacteremia due to other gram-negative pathogens and is discussed elsewhere (see "Gram-negative bacillary bacteremia in adults", section on 'Duration and route of therapy' and "Intravascular non-hemodialysis catheter-related infection: Treatment"). If endocarditis accompanies Acinetobacter bacteremia, duration of therapy is longer and additional considerations exist. (See "Antimicrobial therapy of left-sided native valve endocarditis", section on 'Other gram-negative organisms' and "Antimicrobial therapy of prosthetic valve endocarditis", section on 'Other gram-negative organisms'.)

Meningitis — Variable cerebrospinal fluid (CSF) penetration of antibiotic agents limits the therapeutic choices for Acinetobacter central nervous system infections.

Of the first-line agents, ceftazidime, cefepime, and the carbapenems most reliably enter into the CSF, particularly when inflammation of the meninges is minimal [159]. Because of the association between high-dose imipenem and seizures, meropenem is the preferred choice of the carbapenems. More details regarding antibiotics used to treat gram-negative meningitis are found elsewhere. (See "Health care-associated meningitis and ventriculitis in adults: Treatment and prognosis", section on 'Systemic antimicrobial therapy'.)

For carbapenem-resistant isolates, polymyxins have been used with some success [159]. Because intravenous colistin achieves spinal fluid levels of only 25 percent of serum levels, we add intrathecal (IT) or intraventricular (IVT) colistin for CNS infections being treated with an intravenous polymyxin [92,159,160].

The dose for IT and IVT colistin therapy varies widely in studies [161-165]. Complications include aseptic chemical meningitis or ventriculitis, which may cause increased CSF white blood cell counts and require IT or IVT dose reduction [161]. Dosing and more details regarding colistin IT and IVT polymyxin therapy are found elsewhere (table 3). (See "Health care-associated meningitis and ventriculitis in adults: Treatment and prognosis", section on 'Intrathecal and intraventricular therapy'.)

The role of tigecycline in gram-negative bacillary Acinetobacter meningitis is limited, since tigecycline CSF penetration is only 11 percent of serum levels, and the CSF concentrations after intravenous administration do not reliably exceed the minimum inhibitory concentrations (MICs) of most A. baumannii strains [166,167]. Nevertheless, tigecycline, when used in combination with other antibiotics, has been used successfully to treat meningitis caused by multidrug-resistant Acinetobacter spp [168,169]. The role of minocycline for treatment of meningitis is uncertain, and we only use it in combination therapy and only when no other options are available.

There are few clinical data on the treatment of meningitis with ampicillin-sulbactam. The fraction of the serum concentration that appears in the CSF following sulbactam administration has ranged from less than 1 percent in patients without meningitis to 33 percent in patients with meningitis [170].

Patients whose CNS infection is associated with a CNS device should undergo device removal [171].

For CNS infections due to Acinetobacter, especially those due to multidrug-resistant isolates, consultation with an expert in the management of such infections is advised. More detailed discussion of CNS infections due to gram-negative bacilli is found elsewhere. (See "Health care-associated meningitis and ventriculitis in adults: Treatment and prognosis".)

The response to therapy should be assessed clinically and with repeat CSF cultures, and the duration of therapy for Acinetobacter meningitis is similar to the duration for other gram-negative meningitis infections. These issues are discussed in detail elsewhere. (See "Health care-associated meningitis and ventriculitis in adults: Treatment and prognosis", section on 'Follow-up CSF testing in selected cases' and "Health care-associated meningitis and ventriculitis in adults: Treatment and prognosis", section on 'Duration'.)

Skin, soft tissue, and bone infection — The management of skin, soft tissue, and bone infections caused by Acinetobacter is the same as that for Acinetobacter infections in general, as described elsewhere (see 'Suggested antibiotic regimens' above). In addition, debridement of affected tissue, particularly in the case of osteomyelitis, may be necessary for optimal control of the infection.

The usual duration of therapy for skin and soft tissue infections is shorter than for osteomyelitis and joint infections. For Acinetobacter infections, duration typically matches that of similar infections caused by other pathogens. Details are discussed elsewhere. (See "Nonvertebral osteomyelitis in adults: Treatment" and "Septic arthritis in adults", section on 'Duration' and "Prosthetic joint infection: Treatment", section on 'Duration of therapy'.)

Urinary tract infection — The management of UTIs caused by Acinetobacter is the same as that for Acinetobacter infections in general, except minocycline, tigecycline, and polymyxin B should not be used as monotherapy because they have poor excretion into the urinary tract. If present, any urinary catheter should be removed.

Because Acinetobacter readily colonizes the urinary tract, particularly in the presence of an indwelling catheter, treatment for infection should only be initiated if a positive culture is accompanied by pyuria and systemic signs or symptoms in the absence of another source of infection. Details regarding differentiating colonization from infection are discussed above. (See 'Differentiating colonization from infection' above.)

The duration of therapy is the same as that for other bacterial UTIs, which are discussed elsewhere. (See "Acute simple cystitis in adult and adolescent females" and "Acute complicated urinary tract infection (including pyelonephritis) in adults and adolescents", section on 'Duration'.)

Other infections — Acinetobacter infection of the eye can include corneal ulcers, endophthalmitis, periorbital cellulitis, and infection after penetrating trauma [172-177]. Treatment often consists of topical, subconjunctival, or intravitreal ophthalmic antibiotic preparations, guided by susceptibility results. The duration of treatment is generally similar to that for infections caused by other gram-negative bacilli and depends on the site of infection. (See "Bacterial endophthalmitis" and "Orbital cellulitis".)

Acinetobacter can cause nosocomial sinusitis in patients admitted to the intensive care unit; mechanical ventilation is the most important predisposing factor [178,179]. Treatment of Acinetobacter sinusitis consists of nasal tube removal, sinus drainage and lavage, and antibiotics and is discussed in detail elsewhere. (See "Complications of the endotracheal tube following initial placement: Prevention and management in adult intensive care unit patients", section on 'Sinusitis'.)

Acinetobacter peritonitis has been described in patients undergoing peritoneal dialysis [180-182]. The management of peritonitis in patients undergoing peritoneal dialysis is discussed separately. (See "Microbiology and therapy of peritonitis in peritoneal dialysis".)

PROGNOSIS — Overall mortality from Acinetobacter infection is higher than that associated with most other gram-negative bacilli. In a systematic review of over 2500 patients with Acinetobacter infections from 16 observational studies, the overall mortality rate was 33 percent [183].

Infections due to resistant strains are associated with higher mortality [183-185]. In the aforementioned systematic review, carbapenem resistance was associated with a greater risk of death (pooled odds ratio 2.22, 95% CI 1.66-2.98) [183]. The excess mortality reported from resistant pathogens in this review may have been conflated due to presence of more severe underlying illness or receipt of inappropriate empiric antibiotic therapy in the group with resistant infections.

PREVENTION AND CONTROL — The goals for control of multidrug-resistant Acinetobacter are early recognition, aggressive control of spread, and preventing establishment of endemic strains. General principles of infection control, as well as strategies to prevent health care-associated infections, are essential and are discussed in detail elsewhere. (See "Nosocomial infections in the intensive care unit: Epidemiology and prevention".)

With regards to environmental cleansing, disinfection is particularly important because of the ability of Acinetobacter to survive on inanimate surfaces and contaminate other surfaces that come into contact with it [186]. As an example, in a study of 199 interactions between health care personnel and patients colonized with multidrug-resistant Acinetobacter, 39 percent resulted in contamination of gloves and/or gowns of the health care personnel, a more frequent rate than that observed for multidrug-resistant Pseudomonas [187]. Multidrug-resistant Acinetobacter remains largely susceptible to disinfectants and antiseptics; occasional reports of failure are more likely to represent failure of personnel to follow cleaning procedures than disinfectant resistance [188].

Control is most successful when a common source is identified and eliminated [1,189]. Aggressive and monitored cleaning of environmental reservoirs (using ultraviolet markers of cleaning efficacy) is also important [189]. Hydrogen peroxide vapor has been found to be an effective decontamination method [190]. When neither common sources nor environmental reservoirs are identified, control depends on active surveillance, contact isolation, health care worker compliance with hand hygiene, and aseptic care of vascular catheters and endotracheal tubes [189,191]. (See "Infection prevention: Precautions for preventing transmission of infection".)

SUMMARY AND RECOMMENDATIONS

Antibiotic resistanceAcinetobacter is intrinsically resistant to numerous antibiotics and can accumulate additional mechanisms of resistance that limit antibiotic treatment options. (See 'Antibiotic resistance' above.)

Epidemiology – Globally, resistant strains have become increasingly common. Risk factors for resistance include healthcare exposure and prior exposure to certain antibiotics. (See 'Epidemiology and risk factors' above.)

Differentiating colonization from active infection – Colonization is common and should not be treated. Positive cultures from sterile sites (eg, blood, pleural fluid) should be interpreted as true infection. Cultures from nonsterile sites (eg, urine, lungs) should only be treated if there is clinical evidence of active infection. (See 'Differentiating colonization from infection' above.)

Suggested antibiotic regimens – Regimen selection depends primarily on the severity of the infection and susceptibility of the isolate (algorithm 1).

We categorize potentially active antibiotics as first-line or second-line agents. First-line agents include certain beta-lactam antibiotics, carbapenems, and fluoroquinolones (aminoglycosides and trimethoprim-sulfamethoxazole are first-line agents only for urinary tract infections [UTIs]). Second-line agents primarily include polymyxins (ie, colistin and polymyxin B) and certain tetracycline derivatives (minocycline and tigecycline) (table 2). (See 'Antibiotic efficacy and safety' above.)

Mild infections – These include UTIs and skin and soft tissue infections in the absence of severe sepsis or septic shock. Select cases of pneumonia may be categorized as mild if no systemic symptoms (eg, fever >100.5°F/38°C, tachycardia, tachypnea), hypoxia, mechanical ventilation, or other concerning features are present. (See 'Severity of infection' above.)

For patients with mild infection, we suggest treating with monotherapy with a first-line agent rather than combination therapy (Grade 2C). The choice of agent depends on susceptibility, side effects, and site of infection (algorithm 1 and table 2). (See 'Mild infections' above.)

Moderate to severe infections – These include any infection for which heightened clinical concern is present or the criteria for mild infection are not met. Examples include severe sepsis or septic shock, infections for which source control has not been achieved, or any infection other than UTI, skin and soft tissue infection, or mild pneumonia. (See 'Severity of infection' above.)

For patients with moderate to severe infections, we suggest initial combination antibiotic therapy (Grade 2C). Limited data suggest that it is associated with lower mortality rates. We choose a combination regimen based on the isolate's antibiotic susceptibilities (algorithm 1 and table 2). For most infections, we transition combination therapy to an active single agent once clinical improvement occurs. (See 'Moderate to severe infections' above.)

Disease-specific considerations – Depending on the site of infection (eg, lungs, blood, central nervous system), certain antibiotics should be avoided or adjunctive antibiotics (eg, inhaled formulations for pneumonia, intrathecal formulations for meningitis) may be beneficial. (See 'Disease-specific considerations' above.)

Monitoring for emergent resistance – Because of the possibility of emergence of resistance during therapy, patients who do not respond as expected to therapy should have repeat cultures to evaluate for growth of resistant Acinetobacter isolates. (See 'Monitoring for emergent resistance' above.)

Prognosis – Overall mortality from Acinetobacter infection, especially from multidrug-resistant isolates, is higher than that associated with most other gram-negative bacilli. (See 'Prognosis' above.)

Prevention and control – The goals for control of multidrug-resistant Acinetobacter are early recognition, aggressive control of spread, and preventing establishment of endemic strains. Environmental disinfection is particularly important because Acinetobacter can survive on inanimate surfaces and personal protective equipment worn by health care personnel. (See 'Prevention and control' above.)

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Topic 3150 Version 39.0

References

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