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Stewardship and Emerging Resistance The presence of ESBLs can be inferred by the antibiotic sensi- is more potent against KPC-producing organisms than other tivity pattern (i.e., cefotaxime, ceftazidime, ceftriaxone, or B-lactamase inhibitors), ESBL, and AmpC B-lactamase- cefepime resistance). Intravenous carbapenems are the pre- producing Enterobacteriaceae. Plazomicin is an aminoglyco- ferred option for treating serious infections caused by side with activity against some aminoglycoside-resistant, ESBLs. In addition to several newer antibiotics, tigecycline gram negative organisms; however, it does not provide supe- and ceftazidime-avibactam remain options for treating infec- rior benefit to older aminoglycosides for Pseudomonas or tions caused by KPC-producing gram-negative bacteria. Acinetobacter species (Table 69). Ceftolozane-tazobactam is an option for treating multidrug- resistant P aeruginoso infections. Several older antibiotics retain their activity against some Outpatient Parenteral antibiotic-resistant organisms. Minocycline has activity against Antibiotic Therapy multidrug-resistant Acinetobacter and has been used to treat Outpatient parenteral antibiotic therapy (OPAT) is defined as ventilator-associated pneumonia with an B0'/u clinical response administration of at least two doses of intravenous antibiotics rate. Minocycline is also useful for treating infections caused by on different days without intervening hospitalization. OPAT Stenotrophomonos maltophilio, a problematic pathogen with allows patients to complete parenteral antibiotic therapy at intrinsic antibiotic resistance. In vitro susceptibility to minocy- home or in other outpatient settings when an oral antibiotic is cline can be inferred from susceptibility to tetracycline; how- not appropriate or available. Bone and joint infections are ever, some tetracycline-resistant strains are sensitive to those most commonly treated with OPAT; other candidates minocycline. Fosfomycin is a bactericidal oral antibiotic with include endocarditis, cardiac device infections, abdominal gram-negative and gram-positive activity (including methicillin- infections, skin and soft tissue infections, and antibiotic- resistant S. aureus [MRSA] and vancomycin-resistant resistant infections for which parenteral antibiotics are the Enterococcus [VRE]). It achieves high concentrations in the only option (such as urinary tract infection). urine and may be used to treat cystitis caused by multidrug- Patients should be clinically stable and their infection resistant uropathogens such as VRE and carbapenemase- improving before starting OPAT. When considering OPAI it producing K. pneumonioe. Colistin (polymyxin E) is a bacteri- is important to assess the type of infection being treated, the cidal agent, administered by nebulized aerosol or intravenously, prescribed antibiotic and dosing frequency, the planned that is used to treat multidrug and pan-resistant aerobic, gram- therapy duration, the administration site, the intravenous negative infections, including P. aeruginosa. Proteus, catheter type, and the monitoring process for possible com- Prouidencia, Burkholderia, Morganello, and Serratia species plications. Increasingly, OPAT is being started without initial are resistant to colistin. Colistin resistance has been described in hospitalization after careful medical assessment by a well- some multidrug-resistant gram-negative infections (mostly established and organized OPAT program. OPAT requires carbapenemase-producing K. pneumonio,e). The most com- close monitoring and may include antibiotic levels (vanco- mon adverse effect is nephrotoxicity (up to 50o1, of patients), mycin, aminoglycosides), complete blood count, creatinine which is usually reversible. level, liver chemistry tests, and coagulation tests; patients XEY POIilTS receiving daptomycin therapy in particular should undergo o Minocycline has activity against multidrug-resistant baseline measurement of kidney function and creatine Acinetob acter and Stenotrophomonas maltophilia. kinase level, followed by weekly monitoring. Antibiotic doses and timing should be adjusted based on monitoring . Fosfomycin has gram-negative and gram-positive activ- results. Treatment failure may result from relapse or pro- ity (including methicillin - resist ant Staphglococcus gression of primary infection (60o1, and 21"L, respectively) aure us and vancomyci n- resistant Ente roc o ccus) and and therapeutic complications (tg'/,,). Successful OPAT achieves high concentrations in the urine, making it requires patient participation; supervised infectious dis- useful for treating cystitis. eases OPAT programs have been shown to be safe, efficient, o Nephrotoxicity occurs in up to 50% of patients treated and clinically effective. with colistin, although it is usually reversible. XEY POIT{T . Bone and joint infections are the primary infections Newer Antibaqteria I Drugs treated with outpatient parenteral antibiotic therapy (Opaf)r other candidates for OPAT include serious Two novel tetracycline derivatives, eravacycline and omadacy- infections (endocarditis, cardiac device infections, cline, have activity against many gram-positive (including MRSA and VRE) and gram-negative organisms (including abdominal infections, and skin and soft tissue infec- CRE) as well as anaerobes and atypical bacteria. Meropenem tions) and antibiotic-resistant infections for which parenteral antibiotics are the only option (such as uri- vaborbactam is a combination carbapenem/B-lactamase nary tract infection). inhibitor antibiotic that has activity against KPC (vaborbactam

The presence of ESBLs can be inferred by the antibiotic sensi- is more potent against KPC-producing organisms than other tivity pattern (i.e., cefotaxime, ceftazidime, ceftriaxone, or B-lactamase inhibitors), ESBL, and AmpC B-lactamase- cefepime resistance). Intravenous carbapenems are the pre- producing Enterobacteriaceae. Plazomicin is an aminoglyco- ferred option for treating serious infections caused by side with activity against some aminoglycoside-resistant, ESBLs. In addition to several newer antibiotics, tigecycline gram negative organisms; however, it does not provide supe- and ceftazidime-avibactam remain options for treating infec- rior benefit to older aminoglycosides for Pseudomonas or tions caused by KPC-producing gram-negative bacteria. Acinetobacter species (Table 69). Ceftolozane-tazobactam is an option for treating multidrug- resistant P aeruginoso infections. Several older antibiotics retain their activity against some Outpatient Parenteral antibiotic-resistant organisms. Minocycline has activity against Antibiotic Therapy multidrug-resistant Acinetobacter and has been used to treat Outpatient parenteral antibiotic therapy (OPAT) is defined as ventilator-associated pneumonia with an B0'/u clinical response administration of at least two doses of intravenous antibiotics rate. Minocycline is also useful for treating infections caused by on different days without intervening hospitalization. OPAT Stenotrophomonos maltophilio, a problematic pathogen with allows patients to complete parenteral antibiotic therapy at intrinsic antibiotic resistance. In vitro susceptibility to minocy- home or in other outpatient settings when an oral antibiotic is cline can be inferred from susceptibility to tetracycline; how- not appropriate or available. Bone and joint infections are ever, some tetracycline-resistant strains are sensitive to those most commonly treated with OPAT; other candidates minocycline. Fosfomycin is a bactericidal oral antibiotic with include endocarditis, cardiac device infections, abdominal gram-negative and gram-positive activity (including methicillin- infections, skin and soft tissue infections, and antibiotic- resistant S. aureus [MRSA] and vancomycin-resistant resistant infections for which parenteral antibiotics are the Enterococcus [VRE]). It achieves high concentrations in the only option (such as urinary tract infection). urine and may be used to treat cystitis caused by multidrug- Patients should be clinically stable and their infection resistant uropathogens such as VRE and carbapenemase- improving before starting OPAT. When considering OPAI it producing K. pneumonioe. Colistin (polymyxin E) is a bacteri- is important to assess the type of infection being treated, the cidal agent, administered by nebulized aerosol or intravenously, prescribed antibiotic and dosing frequency, the planned that is used to treat multidrug and pan-resistant aerobic, gram- therapy duration, the administration site, the intravenous negative infections, including P. aeruginosa. Proteus, catheter type, and the monitoring process for possible com- Prouidencia, Burkholderia, Morganello, and Serratia species plications. Increasingly, OPAT is being started without initial are resistant to colistin. Colistin resistance has been described in hospitalization after careful medical assessment by a well- some multidrug-resistant gram-negative infections (mostly established and organized OPAT program. OPAT requires carbapenemase-producing K. pneumonio,e). The most com- close monitoring and may include antibiotic levels (vanco- mon adverse effect is nephrotoxicity (up to 50o1, of patients), mycin, aminoglycosides), complete blood count, creatinine which is usually reversible. level, liver chemistry tests, and coagulation tests; patients XEY POIilTS receiving daptomycin therapy in particular should undergo o Minocycline has activity against multidrug-resistant baseline measurement of kidney function and creatine Acinetob acter and Stenotrophomonas maltophilia. kinase level, followed by weekly monitoring. Antibiotic doses and timing should be adjusted based on monitoring . Fosfomycin has gram-negative and gram-positive activ- results. Treatment failure may result from relapse or pro- ity (including methicillin - resist ant Staphglococcus gression of primary infection (60o1, and 21"L, respectively) aure us and vancomyci n- resistant Ente roc o ccus) and and therapeutic complications (tg'/,,). Successful OPAT achieves high concentrations in the urine, making it requires patient participation; supervised infectious dis- useful for treating cystitis. eases OPAT programs have been shown to be safe, efficient, o Nephrotoxicity occurs in up to 50% of patients treated and clinically effective. with colistin, although it is usually reversible. XEY POIT{T . Bone and joint infections are the primary infections Newer Antibaqteria I Drugs treated with outpatient parenteral antibiotic therapy (Opaf)r other candidates for OPAT include serious Two novel tetracycline derivatives, eravacycline and omadacy- infections (endocarditis, cardiac device infections, cline, have activity against many gram-positive (including MRSA and VRE) and gram-negative organisms (including abdominal infections, and skin and soft tissue infec- CRE) as well as anaerobes and atypical bacteria. Meropenem tions) and antibiotic-resistant infections for which parenteral antibiotics are the only option (such as uri- vaborbactam is a combination carbapenem/B-lactamase nary tract infection). inhibitor antibiotic that has activity against KPC (vaborbactam 104

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