A Greek-English Lexicon. pneumoniaeK. Mayo Clinic Proceedings.

Anti-microbial treatment -

As antiseptics, antimicrobial products are used to treat or prevent diseases on people, pets, and other living things. If a product shows "EPA" anywhere on the label, you know it's a pesticide and NOT meant for use on the body.

This fact sheet will focus on antimicrobials used as pesticides. If a product label claims to kill, control, repel, mitigate or reduce a pest, it is a pesticide regulated by the U. Bleach is a common name for products that contain sodium hypochlorite.

Bleach may be a pesticide, a cleaner, or both. There are two general categories for antimicrobial pesticides: those that address microbes in public health settings, and those that do not.

See Table 1. There are three types of public health antimicrobials: sterilizers, disinfectants, and sanitizers. See Table 2. Sanitizers are the weakest public-health antimicrobials. They reduce bacteria on surfaces. The label will indicate how a sanitizer can be used. Some sanitizers can be used only for non-food contact surfaces like toilet bowls and carpets, or air.

Disinfectants kill or prevent the growth of bacteria and fungi. Some disinfectants target specific viruses. Disinfectants are also used in residential settings. Different products purify swimming pools and disinfect household surfaces such as linens, toilets, and bathtubs.

Whether disinfectants are used in medical or residentials settings, or elsewhere, they may not be used on surfaces that come in contact with food.

Table 2. Three main types of public health antimicrobial pesticides a Sanitizer Disinfectant Sterilizer Effective against Sprays, liquids, gels, granules, etc. Liquid, gases a This table contains generalized information. Always read the product label to determine where and how a product should be used.

In addition to bacteria, algae, and fungi, they also control hard-to-kill spores. These require applicator training and certification. Sterilizers are used in medical and research settings when the presence of microbes must be prevented as much as possible.

In addition to chemical sterilizers, high-pressure steam and ovens are also used to sterilize items. Limited numbers of patients received cefoxitin or cefotetan in published studies [, , ]. The panel believes more clinical data associated with these agents for the treatment of ESBL-E infections is necessary before advocating for their use—including optimal dosing and frequency of administration—especially in light of the two observational studies suggesting poorer clinical outcomes with cephamycin use.

Data suggest more favorable outcomes with high-dose, continuous infusion cefoxitin i. As both cefotetan and cefoxitin are only available IV and have relatively short half-lives, there does not appear to be a feasibility advantage with use of these agents over preferred agents for the treatment of ESBL-E infections.

Suggested approach: The panel suggests that ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol be preferentially reserved for treating infections caused by organisms exhibiting carbapenem resistance.

The panel suggests against the use of ceftolozane-tazobactam for the treatment of ESBL-E infections, with the possible exception of polymicrobial infections.

Ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol exhibit activity against ESBL-E []. Avibactam is able to successfully protect ceftazidime against hydrolysis by ESBL enzymes []. Clinical trial data support ceftazidime-avibactam effectiveness against ESBL-E infections [].

The carbapenem component of meropenem-vaborbactam and imipenem-cilastatin-relebactam provide sufficient activity against ESBL-E, even without the addition of a β-lactamase inhibitor.

Although ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol are expected to be effective against ESBL-E infections, the panel suggests that these agents be preferentially reserved for treating infections caused by organisms exhibiting carbapenem resistance, where a greater need for these agents exists.

aeruginosa and ESBL-E; ceftazidime-avibactam or cefiderocol in settings of concomitant valproic acid use []. Ceftolozane-tazobactam frequently exhibits in vitro activity against ESBL-E [].

Additionally, clinical data indicate it may be effective for the treatment of ESBL-E infections []. However, the panel remains concerned with the ability of tazobactam to successfully inhibit ESBL production as discussed in Question 1.

The panel suggests against the use of ceftolozane-tazobactam for the treatment of ESBL-E infections. In polymicrobial infections in which DTR- P. aeruginosa and ESBL-E are isolated, the use of ceftolozane-tazobactam can be considered, after weighing the pros and cons of this approach, to limit exposure to multiple agents and their associated toxicities.

However, if this approach is taken, close monitoring of patients for an appropriate clinical response is advised. AmpC β-lactamases are β-lactamase enzymes that are produced at basal levels by a number of Enterobacterales and glucose non-fermenting gram-negative organisms. Their primary function is to assist with cell wall recycling [].

AmpC β-lactamases are capable of hydrolyzing a number of β-lactam agents, some in settings of basal AmpC production and others in settings of increased AmpC production.

Increased AmpC production by Enterobacterales generally occurs by one of three mechanisms: 1 inducible chromosomal gene expression, 2 stable chromosomal gene de-repression, or 3 constitutively expressed ampC genes frequently carried on plasmids, but sometimes integrated into the chromosome [, ].

In this document, we will focus on the treatment of infections by Enterobacterales species with a moderate to high likelihood of inducible ampC gene expression [, ]. Increased AmpC enzyme production resulting from inducible ampC expression can occur in the presence of specific antibiotics and results in sufficient enzyme in the periplasmic space to increase MICs to certain antibiotics, most notably ceftriaxone, cefotaxime, and ceftazidime.

In this scenario, an Enterobacterales isolate that initially tests as susceptible to ceftriaxone may exhibit non-susceptibility to this agent after treatment with ceftriaxone is initiated.

In this guidance document, such organisms are described as having a moderate to high risk for clinically significant AmpC production. Resistance due to ampC induction can be observed after even a few doses of ceftriaxone, cefotaxime, or ceftazidime [].

For the other two mechanisms i. As such, infections by these organisms generally pose less of a treatment dilemma than infections caused by isolates with inducible ampC expression. Regarding the first of these two mechanisms, some Enterobacterales isolates e.

contain mutations in promoters or attenuators of ampC or other related genes e. For the second mechanism, constitutive expression of ampC genes e. pneumoniae , and Salmonella spp. These ampC genes can be found either on plasmids or be integrated into the bacterial chromosome.

Suggested approach : Enterobacter cloacae complex, Klebsiella aerogenes , and Citrobacter freundii are the most common Enterobacterales at moderate to high risk for clinically significant AmpC production.

Quantifying the likelihood of ampC induction across bacterial species would be best defined by systematically identifying organisms initially susceptible to certain β-lactam agents e. Unfortunately, such studies are not available.

For example, Citrobacter freundii harbors a chromosomal ampC whereas Citrobacter koseri does not []. Indole-positive Proteus spp. currently refers to organisms such as P. vulgaris and P.

penneri , which generally do not contain chromosomal ampC genes. The emergence of clinically relevant ampC expression during antibiotic treatment has been most frequently described for E. cloacae complex herein, referred to as E.

cloacae for simplicity , K. aerogenes formerly Enterobacter aerogenes , and C. These clinical observations mirror in vitro mutation rate analyses, which also suggest that these organisms are likely to overexpress ampC [].

Therefore, when E. cloacae , K. aerogenes , or C. freundii are recovered in clinical cultures other than urine cultures in uncomplicated cystitis , the panel suggests avoiding treatment with ceftriaxone or ceftazidime, even if an isolate initially tests susceptible to these agents Question 2.

In contrast, other organisms historically presumed to be at risk for the development of clinically significant ampC expression, such as Serratia marcescens, Morganella morganii, and Providencia spp. When S. marcescens , M.

morgannii , or Providencia spp. are recovered from clinical cultures, the panel suggests selecting antibiotic treatment according to AST results. A number of less commonly encountered pathogens e.

As such, descriptions of their potential for clinically significant AmpC production are very limited. It is reasonable to use AST results to guide treatment decisions if these organisms are recovered in clinical cultures e. When treating infections caused by these less commonly recovered organisms or caused by S.

marcescens, M. morgannii, or Providencia spp. with a high bacterial burden and limited source control e. As with all infections, if an adequate clinical response is not observed after appropriately dosed antibiotic therapy is initiated and necessary source control measures are taken, clinicians should consider the possibility of the emergence of resistance to the initially prescribed agent.

Suggested approach: Several β-lactam antibiotics are at relatively high risk of inducing ampC genes. Both the ability to induce ampC genes and the inability to withstand AmpC hydrolysis should inform antibiotic decision-making.

β-lactam antibiotics fall within a spectrum of potential for inducing ampC genes. Aminopenicillins i. However, organisms at moderate to high risk for clinically significant ampC induction e. Therefore, such AmpC-E isolates will generally test as non-susceptible to these drugs, averting treatment dilemmas.

Imipenem is also a potent ampC inducer but it generally remains stable to AmpC-E hydrolysis because of the formation of stable acyl enzyme complexes []. The induction potential of ertapenem and meropenem has not been formally investigated but, similar to imipenem, they are generally stable to AmpC hydrolysis [, ].

Piperacillin-tazobactam, ceftriaxone, ceftazidime, and aztreonam are relatively weak ampC inducers [, ]. Available evidence indicates that despite their limited ability to induce ampC , the susceptibility of these agents to hydrolysis makes them unlikely to be effective for the treatment of infections by organisms at moderate to high risk for clinically significant AmpC production [, ].

Cefepime has the advantage of both being a weak inducer of ampC and of withstanding hydrolysis by AmpC β-lactamases because of the formation of stable acyl enzyme complexes [, ]. Therefore, cefepime is generally an effective agent for the treatment of AmpC-E infections [].

TMP-SMX, fluoroquinolones, aminoglycosides, tetracyclines, and other non-beta-lactam antibiotics do not induce ampC and are also not substrates for AmpC hydrolysis. Suggested approach: Cefepime is suggested for the treatment of infections caused by organisms at moderate to high risk of significant AmpC production i.

cloacae complex, K. aerogenes , and C. Cefepime is an oxyimino-cephalosporin that is relatively stable against AmpC enzymes and that also has low ampC induction potential [, , , ]. However, several case reports of therapeutic failure of cefepime against infections caused by AmpC-E have led to hesitancy in prescribing this agent [].

Understanding the contribution of AmpC production to cefepime clinical failure in these case reports is challenging as cefepime was generally dosed every 12 hours as opposed to every 8 hours , co-production of ESBL enzymes was rarely investigated, and outer membrane porin mutations were often identified — also elevating carbapenem MICs i.

Clinical trials comparing clinical outcomes of patients with AmpC-E infections treated with cefepime versus carbapenem therapy are not available. However, several observational studies suggest cefepime is associated with similar clinical outcomes as carbapenem therapy [, , ].

Furthermore, a meta-analysis including seven studies comparing clinical outcomes of patients receiving cefepime versus carbapenems for Enterobacter spp. bloodstream infections did not find differences in clinical outcomes between these treatment regimens, although considerable heterogeneity between studies existed, ill appearing patients were more likely to receive carbapenem therapy, and risk of AmpC production varied by the included species [].

In light of both the advantages of cefepime as a compound and no clear clinical failure signals in the literature when administered for the treatment of AmpC-E infections, the panel suggests cefepime as a preferred treatment option for E.

freundii infections Table 1. Although cefepime may be effective for the treatment of AmpC-E infections, it remains suboptimal against infections caused by ESBL-E [92, ].

The same study evaluated patients with E. A small, single-center United States study also suggests that the likelihood of ESBL production increases in E.

cloacae as cefepime MICs increase []. Contemporary data specific to the United States are needed to better understand how frequently ESBLs are produced by Enterobacterales at moderate to high risk of clinically significant AmpC production.

However, in light of available data, we advise caution with administering cefepime for infections caused by E. Suggested approach: Ceftriaxone or cefotaxime or ceftazidime is not suggested for the treatment of invasive infections caused by organisms at moderate to high risk of clinically significant AmpC production e.

Ceftriaxone is a reasonable for uncomplicated cystitis caused by these organisms when susceptibility is demonstrated.

Clinical reports differ on how frequently resistance to ceftriaxone emerges during the treatment of infections by Enterobacterales at moderate to high risk for clinically significant ampC induction.

Several challenges exist when interpreting studies that have attempted to address this question. First, there are no CLSI-endorsed approaches for AmpC detection in clinical isolates, making their accurate identification difficult. Second, these organisms may display ceftriaxone non-susceptibility for other reasons e.

oxytoca , and P. Third, studies often combine estimates for organisms at low risk for significant AmpC production e. morgannii with those posing a higher risk e.

cloacae , C. freundii , obscuring our understanding of how frequently resistance to ceftriaxone emerges for organisms truly at high risk for AmpC production [].

Fourth, studies that evaluate the proportion of isolates exhibiting ceftriaxone non-susceptibility after ceftriaxone exposure do not include confirmation of genetic relatedness of index and subsequent isolates.

Additionally, most AmpC clinical studies use pre CLSI ceftriaxone breakpoints i. Finally, there is significant heterogeneity in sources of infections, severity of illness, pre-existing medical conditions, co-administration of additional antibiotics, and ceftriaxone dosing and duration across studies, complicating the interpretation of clinical data.

freundii [, ] , []. Comparative effectiveness studies addressing the management of presumed AmpC producing infections have mostly focused on the emergence of ceftriaxone resistance, rather than on clinical outcomes.

Clinical trials have not compared the clinical outcomes of patients with presumed AmpC-E infections treated with ceftriaxone compared to alternate agents i. A number of observational studies compared the clinical outcomes of patients with infections caused by E. freundii treated with ceftriaxone compared with other β-lactams [, , , ].

The most rigorous of these studies is a multicenter observational study that included patients with bloodstream infections caused by Enterobacter spp.

Similar to the other observational studies evaluating this question, this study did not identify differences in clinical outcomes when comparing patients treated with ceftriaxone versus carbapenems.

However, this study had several of the limitations outlined above. Nonetheless, since available data indicate a reasonable risk for the emergence of resistance when ceftriaxone or ceftazidime is prescribed for infections caused by organisms at moderate to high risk of AmpC production i.

aerogenes , C. freundii , the panel suggests generally avoiding ceftriaxone or ceftazidime when treating infections caused by these organisms. Based on the mild nature of uncomplicated cystitis and the sufficient urinary excretion of ceftriaxone, ceftriaxone may be adequate therapy for the management of AmpC-E cystitis.

Preferred treatment options for AmpC-E cystitis are described in Question 2. Suggested approach : Piperacillin-tazobactam is not suggested for the treatment of serious infections caused by Enterobacterales at moderate to high risk of clinically significant inducible AmpC production.

Tazobactam is less effective at protecting β-lactams from AmpC hydrolysis than newer β-lactamase inhibitors, such as avibactam, relebactam, and vaborbactam [, , , ].

The role of piperacillin-tazobactam in treating Enterobacterales at moderate to high risk for clinically significant AmpC production remains uncertain. A meta-analysis summarized the findings of eight observational studies and did not identify a difference in mortality between patients treated with piperacillin-tazobactam and carbapenems for bacteremia by Enterobacter spp.

In an observational study of patients published subsequent to the meta-analysis, piperacillin-tazobactam monotherapy was associated with over twice the odds of death within days, compared to alternative agents [].

A pilot unblinded clinical trial compared the outcomes of 72 patients with bloodstream infections caused by Enterobacter spp. aerogenes, C.

freundii , M. morganii , Providencia spp. marcescens randomized to piperacillin-tazobactam 4. There were no significant differences in the primary outcome a composite outcome including day mortality, clinical failure, microbiological failure, or microbiological relapse between the study arms.

The findings of this trial are challenging to interpret and a larger trial is needed to more definitively determine the role of piperacillin-tazobactam for the treatment of organisms at moderate to high risk for clinically significant ampC induction. In light of the limited ability of tazobactam to protect piperacillin from AmpC hydrolysis in vitro and at least three observational studies identifying increased mortality in patients prescribed piperacillin-tazobactam [, , ] , the panel suggests caution if prescribing piperacillin-tazobactam for serious infections caused by AmpC-E.

Piperacillin-tazobactam may be a reasonable treatment option for mild infections such as uncomplicated cystitis. The panel does not suggest the use of ceftolozane-tazobactam as a treatment option for AmpC-E infections, with the possible exception of polymicrobial infections.

Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-cilastatin-relebactam generally exhibit in vitro activity against AmpC-E [, , ]. Although ceftazidime-avibactam is likely to be effective as a treatment for infections caused by AmpC-E, some data suggest it may have slightly higher failure rates for the treatment of AmpC-E infections compared to ESBL-E infections [].

Although the frequency is unknown, emergence of resistance of AmpC-E to ceftazidime-avibactam has been described [, ]. Cefiderocol demonstrates in vitro activity against AmpC-E [, ] and it is likely to be effective in clinical practice, although some case reports indicate the potential for AmpC-E to develop resistance to the drug [, ].

Although ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol are likely to be effective against AmpC-E infections, the panel suggests that these agents be preferentially reserved for treating infections caused by organisms exhibiting carbapenem resistance, where a greater need for them exists.

Tazobactam appears less effective at protecting β-lactams from AmpC hydrolysis compared with newer β-lactamase inhibitors, such as avibactam, relebactam, and vaborbactam [, , , ]. cloacae isolates []. Clinical outcomes data for ceftolozane-tazobactam for the treatment of AmpC-E infections are limited; a clinical trial evaluating this question is underway [].

In light of the concerns described for tazobactam inhibition in Question 2. aeruginosa and AmpC-E are isolated, the use of ceftolozane-tazobactam can be considered, after weighing the pros and cons of this approach, to limit exposure to multiple agents and their associated toxicities.

Suggested approach: Nitrofurantoin or TMP-SMX a re preferred treatment options for uncomplicated AmpC-E cystitis. Aminoglycosides are alternative treatments for uncomplicated cystitis, pyelonephritis, and cUTI caused by AmpC-E.

TMP-SMX or fluoroquinolones can be considered for the treatment of invasive infections caused by organisms at moderate to high risk of clinically significant AmpC production. Preferred treatment options for AmpC-E uncomplicated cystitis include nitrofurantoin [19] or TMP-SMX [38, ].

Ciprofloxacin or levofloxacin are alternative treatment options. A single IV dose of an aminoglycoside is an alternative treatment for AmpC-E uncomplicated cystitis [27]. Aminoglycosides are nearly exclusively eliminated by the renal route in their active form. A single IV dose is generally effective for uncomplicated cystitis, with minimal toxicity, but robust clinical outcomes data are limited [27].

In patients in whom the potential for nephrotoxicity is deemed acceptable, aminoglycosides dosed based on therapeutic drug monitoring results for a full treatment course are an alternative option for the treatment of AmpC-E pyelonephritis or cUTI [39, 40] Table 1 , Supplemental Material.

The role of TMP-SMX or fluoroquinolones for the treatment of AmpC-E infections outside of the urinary tract has not been formally evaluated in clinical trials or robust observational studies. However, neither TMP-SMX nor fluoroquinolones are substrates for AmpC hydrolysis.

Oral step-down therapy with TMP-SMX or fluoroquinolones have been shown to be reasonable treatment considerations for Enterobacterales bloodstream infections, including those caused by AmpC-E, after appropriate clinical milestones are achieved [60, 61].

Based on the known bioavailability and sustained serum concentrations of oral TMP-SMX and fluoroquinolones, these agents are treatment options for patients with AmpC-E infections if 1 susceptibility to an appropriate oral agent is demonstrated, 2 patients are hemodynamically stable, 3 reasonable source control measures have occurred, and 4 concerns about insufficient intestinal absorption are not present.

The panel advises avoiding oral step-down to nitrofurantoin, fosfomycin, doxycycline, or amoxicillin-clavulanate for AmpC-E bloodstream infections. CRE account for more than 13, infections and contribute to greater than 1, deaths in the United States annually [].

The CDC defines CRE as members of the Enterobacterales order resistant to at least one carbapenem antibiotic or producing a carbapenemase enzyme []. Resistance to at least one carbapenem other than imipenem is required for bacteria generally not susceptible to imipenem e. For the purposes of this guidance document, CRE refers to organisms displaying resistance to either meropenem or imipenem, or those Enterobacterales isolates producing carbapenemase enzymes Question 3.

CRE comprise a heterogenous group of pathogens encompassing multiple mechanisms of resistance, broadly divided into those that are not carbapenemase-producing and those that are carbapenemase-producing.

CRE that are not carbapenemase-producing may be the result of amplification of non-carbapenemase β-lactamase genes e. The most common carbapenemases in the United States are K. pneumoniae carbapenemases KPCs , which are not limited to K.

pneumoniae isolates. Other notable carbapenemases that have been identified in the United States include New Delhi metallo-β-lactamases NDMs , Verona integron-encoded metallo-β-lactamases VIMs , imipenem-hydrolyzing metallo-β-lactamases IMPs , and oxacillinases e.

Knowledge of whether a CRE isolate is carbapenemase-producing and, if it is, the specific carbapenemase produced is important in guiding treatment decisions. Phenotypic tests such as the modified carbapenem inactivation method differentiate carbapenemase and non-carbapenemase-producing CRE [].

Molecular testing can identify specific carbapenemase gene families e. Treatment suggestions for CRE infections listed below assume that in vitro activity of preferred and alternative antibiotics has been demonstrated. Suggested approach: For infections caused by Enterobacterales isolates that exhibit susceptibility to meropenem and imipenem i.

In this guidance document, CRE refers to Enterobacterales isolates resistant to meropenem or imipenem or Enterobacterales producing a carbapenemase enzyme. Questions 3. For infections caused by Enterobacterales isolates that exhibit susceptibility to meropenem and imipenem i.

Standard-infusion meropenem or imipenem-cilastatin may be reasonable for uncomplicated cystitis Table 1. For isolates susceptible to meropenem but not susceptible to imipenem and vice versa , in the absence of data to inform the optimal treatment approach, the panel suggests basing the treatment decision on the severity of illness of the patient and site of infection.

For example, in this scenario, meropenem may be a reasonable treatment for urinary tract infection but not for a complex intra-abdominal infection.

The panel suggests against the use of meropenem-vaborbactam or imipenem-cilastatin-relebactam to treat ertapenem-resistant, meropenem-susceptible and imipenem-susceptible infections since these agents are unlikely to offer any substantial benefit beyond that of extended-infusion meropenem or imipenem-cilastatin alone.

Suggested approach: Nitrofurantoin, TMP-SMX, ciprofloxacin, or levofloxacin are preferred treatment options for uncomplicated cystitis caused by CRE, although the likelihood of susceptibility to any of these agents is low.

A single dose of an aminoglycoside, oral fosfomycin for E. coli only , colistin, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, cefiderocol, are alternative treatment options for uncomplicated cystitis caused by CRE.

Clinical trial data evaluating the efficacy of most preferred agents for uncomplicated CRE cystitis are not available. However, as nitrofurantoin, TMP-SMX, ciprofloxacin, or levofloxacin all achieve high concentrations in urine, they are expected to be effective for uncomplicated CRE cystitis, if the isolate is susceptible [4, ].

A single dose of an aminoglycoside is an alternative option for CRE uncomplicated cystitis. Aminoglycosides are almost exclusively eliminated by the renal route in their active form. A single IV dose is generally effective for cystitis, with minimal toxicity [27]. In general, higher percentages of CRE clinical isolates are susceptible to amikacin and plazomicin than to other aminoglycosides [, ].

Plazomicin may remain active against isolates resistant to other aminoglycosides []. Oral fosfomycin is an alternative option for the treatment of uncomplicated CRE cystitis caused by E. coli as the fosA gene intrinsic to many gram-negative organisms can hydrolyze fosfomycin and may lead to clinical failure [28, 29].

Clinical trial data indicate that a single dose of oral fosfomycin is associated with higher clinical failure than a five-day course of nitrofurantoin for uncomplicated cystitis [19].

Colistin the active form of the commercially available parenteral inactive prodrug colistimethate sodium is an alternative agent for treating uncomplicated CRE cystitis.

Colistin converts to its active form in the urinary tract; clinicians should remain cognizant of the associated risk of nephrotoxicity [].

Polymyxin B should not be used as treatment for uncomplicated CRE cystitis, due to its predominantly nonrenal clearance []. Ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol are alternative options for uncomplicated CRE cystitis.

They are designated alternative agents to preserve their activity for more invasive CRE infections. Data are insufficient to favor one agent over the others but all of these agents are reasonable treatment options based on published comparative effectiveness studies [, ].

Suggested approach: TMP-SMX, c iprofloxacin, or levofloxacin are preferred treatment options for pyelonephritis and cUTI caused by CRE, if susceptibility is demonstrated.

Ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol are also preferred treatment options for pyelonephritis and cUTIs. Aminoglycosides are alternative treatment options.

Although the minority of CRE are expected to retain susceptibility to TMP-SMX, ciprofloxacin, or levofloxacin, these agents are all preferred agents to treat CRE pyelonephritis or cUTI if susceptibility is demonstrated []. Ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol are preferred treatment options for pyelonephritis and cUTIs caused by CRE based on clinical trials showing non-inferiority of these agents to common comparator agents for UTIs [, ].

Isolates included in these trials were overwhelmingly carbapenem susceptible. Data are insufficient to favor one agent over the others. In patients in whom the potential for nephrotoxicity is deemed acceptable, aminoglycosides for a full treatment course are an alternative option for the treatment of CRE pyelonephritis or cUTI [].

Table 1 , Supplemental Material. Suggested approach: Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-cilastatin-relebactam are the preferred treatment options for infections outside of the urinary tract caused by CRE, when carbapenemase testing results are either not available or negative.

For patients with CRE infections who within the previous 12 months have received medical care in countries with a relatively high prevalence of metallo-β-lactamase-producing organisms or who have previously had a clinical or surveillance culture where a metallo-β-lactamase-producing isolate was identified, preferred treatment options include the combination of ceftazidime-avibactam plus aztreonam, or cefiderocol as monotherapy, while awaiting AST results to the novel β -lactam agents and carbapenemase testing results.

Ceftazidime-avibactam has activity against most KPC- and OXAlike-producing CRE isolates [, ]. Meropenem-vaborbactam and imipenem-cilastatin-relebactam are active against most Enterobacterales that produce KPC enzymes but not those that produce OXAlike carbapenemases [].

Neither ceftazidime-avibactam, meropenem-vaborbactam, nor imipenem-cilastatin-relebactam have activity against metallo-β-lactamase e.

As described above, the vast majority of CRE clinical isolates in the United States either do not produce carbapenemases or, if they do, produce KPCs. Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-cilastatin-relebactam all have a high likelihood of activity against CRE that do not produce carbapenemases [, ].

There do not appear to be differences in the effectiveness of these agents when susceptibility has been demonstrated. Cefiderocol is suggested as an alternative treatment option for CRE infections outside of the urine.

Cefiderocol is a synthetic conjugate composed of a cephalosporin moiety and a catechol-type siderophore, which binds to iron and facilitates bacterial cell entry using active iron transporters [].

Once inside the periplasmic space, the cephalosporin moiety dissociates from iron and binds primarily to PBP3 to inhibit bacterial cell wall synthesis [].

Cefiderocol is highly likely to be active against CRE clinical isolates as it exhibits activity against Enterobacterales producing any of the five major carbapenemase enzymes, as well as CRE isolates not producing carbapenemases [, ].

In an effort to preserve cefiderocol activity for infections caused by pathogens where other β-lactam agents may have little to no activity, such as those caused by metallo- β -lactamase-producing Enterobacterales or by non-fermenting gram-negative organisms, the panel suggests cefiderocol as an alternative agent for infections caused by non-metallo- β -lactamase producing CRE.

Patients with CRE infections who have received medical care in countries with a relatively high prevalence of metallo-β-lactamase-producing CRE within the previous 12 months [] or who previously had a clinical or surveillance culture where metallo-β-lactamase-producing organisms were identified have a high likelihood of being infected with metallo-β-lactamase-producing Enterobacterales.

For such patients if carbapenemase results are not yet available , preferred treatment options include the combination of ceftazidime-avibactam plus aztreonam, or cefiderocol as monotherapy Question 3.

Tigecycline or eravacycline are alternative options for the treatment of CRE infections not involving the bloodstream or urinary tract Question 3. Their activity is independent of the presence or type of carbapenemase. However, subsequent observational and trial data indicate increased mortality and excess nephrotoxicity associated with polymyxin or aminoglycoside-based regimens relative to newer β-lactam-β-lactamase inhibitor agents for the treatment of CRE infections [].

Therefore, the panel advises against the use of extended-infusion carbapenems with or without the addition of a second agent for the treatment of CRE infections.

Suggested approach: Meropenem-vaborbactam, ceftazidime-avibactam, and imipenem-cilastatin-relebactam are preferred treatment options for KPC-producing infections. Cefiderocol is an alternative option. Preferred agents for KPC-producing infections include meropenem-vaborbactam, ceftazidime-avibactam, or imipenem-cilastatin-relebactam [, , , ].

Although all three agents are preferred agents for the treatment of KPC-producing infections, the panel slightly favors meropenem-vaborbactam, followed by ceftazidime-avibactam, and then imipenem-cilastatin-relebactam, based on available data regarding clinical outcomes and emergence of resistance.

These agents are associated with improved clinical outcomes and reduced toxicity compared to other regimens commonly used to treat KPC-producing infections, which are often polymyxin-based [, ].

Clinical trials comparing these agents to each other for the treatment of KPC-producing infections are not available. An observational study compared the clinical outcomes of patients who received either meropenem-vaborbactam or ceftazidime-avibactam for at least 72 hours for the treatment of CRE infections [].

Carbapenemase status was largely unavailable. Although these differences were not statistically significant, they numerically favor meropenem-vaborbactam. This study had a number of important limitations: likely selection bias due to its observational nature, relatively small numbers of patients, heterogenous sites of CRE infection, more than half of patients had polymicrobial infections, and more than half of patients received additional antibiotic therapy.

These limitations notwithstanding, this study suggests that both meropenem-vaborbactam and ceftazidime-avibactam are reasonable treatment options for KPC-producing infections, although the emergence of resistance may be more common with ceftazidime-avibactam Question 3.

At least two groups that have published their clinical experiences with the use of ceftazidime-avibactam and meropenem-vaborbactam similarly found that patients who received meropenem-vaborbactam had a slightly higher likelihood of clinical cure and survival and a lower risk of emergence of resistance than patients treated with ceftazidime-avibactam [].

Limited clinical data are available for imipenem-cilastatin-relebactam compared with the other novel β-lactam-β-lactamase inhibitor agents. A clinical trial including patients with infections caused by gram-negative organisms not susceptible to imipenem assigned patients to receive either imipenem-cilastatin-relebactam versus imipenem-cilastatin and colistin [].

It is difficult to draw meaningful conclusions from these data given the small numbers. However, in vitro activity of imipenem-cilastatin-relebactam against CRE [, ] , clinical experience with imipenem-cilastatin, and the stability of relebactam as a β-lactamase inhibitor [] suggest imipenem-cilastatin-relebactam is likely to be effective for CRE infections if it tests susceptible.

Cefiderocol is an alternative treatment option for KPC-producing Enterobacterales []. Example: Aspergillus fumigatus changes the cyp1A gene so that triazoles cannot bind to the protein.

Example: Some Staphylococcus aureus bacteria can bypass the drug effects of trimethoprim. Skip directly to site content Skip directly to search. Español Other Languages. How Antimicrobial Resistance Happens Minus Related Pages. Germs are microbes—very small living organisms including bacteria, fungi, parasites, and viruses.

Most germs are harmless and even helpful to people, but some can cause infections. Harmful germs are called pathogens. Antimicrobials is a term used to describe drugs that treat many types of infections by killing or slowing the growth of pathogens causing the infection.

The content on this webpage does not include resistance to antivirals or antiparasitics. Bacteria cause infections such as strep throat, foodborne illnesses, and other serious infections.

Antibiotics treat bacterial infections. Antifungals treat fungal infections. On This Page. How Antibiotic and Antifungal Use Affects Resistance Antibiotics and antifungals save lives, but their use can contribute to the development of resistant germs.

Resistance Mechanisms Defense Strategies Resistance Mechanisms Defense Strategies Description Restrict access of the antibiotic Germs restrict access by changing the entryways or limiting the number of entryways. Get rid of the antibiotic or antifungal Germs get rid of antibiotics using pumps in their cell walls to remove antibiotic drugs that enter the cell.

Change or destroy the antibiotic Germs change or destroy the antibiotics with enzymes, proteins that break down the drug.

Change the targets for the antibiotic or antifungal Many antibiotic drugs are designed to single out and destroy specific parts or targets of a bacterium. Fact Sheets. How Resistance Spreads.

Antimicrobial resistance AMR High protein low carb diet a Anti-kicrobial Anti-microbial treatment. Anti-microhial, approximately 1. In the Treatmebt States, antimicrobial Antu-microbial pathogens caused Anti-microbial treatment than 2. The Anti-microbial treatment Diseases Society of America IDSA identified the development and Anti-microbial treatment of Anti-microbial treatment practice guidelines Anfi-microbial other guidance documents as a top initiative in its Strategic Plan [3]. IDSA acknowledged that the ability to address rapidly evolving topics such as AMR was limited by prolonged timelines needed to generate new or updated clinical practice guidelines, which are based on systematic literature reviews and employ GRADE Grading of Recommendations Assessment, Development, and Evaluation methodology. Additionally, when clinical trial data and other robust studies are limited or not available, the development of clinical practice guidelines is challenging. Anti-jicrobial antimicrobial is an agent that kills microorganisms microbicide or stops their Greatment bacteriostatic Anti-microbial treatment. For example, antibiotics are Anti-microbial treatment against bacteriaand antifungals are used Anti-jicrobial fungi. They Pre-workout meal planning guide also be Anti-microbial treatment Antk-microbial to their Anti-microbial treatment. Traetment use of antimicrobial medicines to treat infection is known as antimicrobial chemotherapywhile the use of antimicrobial medicines to prevent infection is known as antimicrobial prophylaxis. The main classes of antimicrobial agents are disinfectants non-selective agents, such as bleachwhich kill a wide range of microbes on non-living surfaces to prevent the spread of illness, antiseptics which are applied to living tissue and help reduce infection during surgeryand antibiotics which destroy microorganisms within the body.