2. 12) Non-infectious causes of fever – DVT’s, hematoma, drug fever, malignancy,  transfusion reactions, pancreatitis, and more Vilay AM, Grio M, Depestel DD, Sowinski KM, Gao L, Heung M, et al. water exposures, animal bites, neutropenia). Nitrofurantoin 100 mg po bid x 5 days (contraindicated in renal failure), or + It appears to be effective in several studies, although this remains a bit controversial. 4. In one study of patients treated for osteomyelitis, Moenster and colleagues 5 reported the incidence of AKI for vancomycin + PT (VPT) and vancomycin + cefepime (VC) to be 31.2% and 19.5%, respectively, but this difference was not statistically significant. In addition to surgical drainage, empiric antibiotics based on gram stain:  Also effective vs anthrax. caspofungin) if severely ill and high risk of Candida (e.g TPN, immunocompromised). III. 2. Combination therapy of low-dose beta-lactam with an aminoglycoside achieves very good response rates and low rates of toxicity. IV. 8) Viral Infections – Influenza, HSV/VZV/CMV etc. 3. 7-21 days if no evidence of osteomyelitis. Only Ciprofloxacin and Levofloxacin come in PO form, all other are IV only. Load 200 mg IV once, then 100 mg IV qday. 2. Included are drugs with activity against MRSA, Coag-negative staph, Streptococci, Enterococcus including VRE (except Vancomycin). Used for: respiratory infections (upper and lower tract), gonorrhea, UTIs, Lyme disease (alternative to Doxycycline), and more. (HAP, HCAP, VAP). Oral options: Cephalexin 500 mg po q6 hours, Clindamycin, Dicloxacillin. If mildly ill – Ciprofloxacin 400 mg IV q12 hrs or Levofloxacin 500 mg IV q24 hrs or Ceftriaxone 1 g IV q24 hrs. Cefepime has been shown to have similar efficacy as carbapenems for Enterobacter infections, with no differences in bacteremia duration, length of … There was a slight difference in length of admission (13 vs 10 days, P = 0.042), but no difference in days to ... AKI occurred in nearly 55% of patients with piperacillin‐tazobactam therapy versus 13% of patients with cefepime therapy, which suggests cefepime may be preferred in combination with vancomycin and tobramycin for pediatric CF patients. Oral Vancomycin – first-line therapy for severe C.diff infection (WBC >15k, or acute renal failure).  Shown to be superior in severe cases of C.diff vs Metronidazole (CID 2007). Â, 3. 1. Despite broad spectrum, only used for select indications. 2006; 26: 1320-32. IRB approval from a single CF center was obtained for this retrospective cohort study. Overall, treatment groups were balanced with respect to baseline characteristics, although more patients in the meropenem group had diabetes (41.4% vs 31.4%), a urinary tract source for BSI (67.0% vs 54.8%), and higher APACHE II scores (21.0 vs 17.9). Staph aureus is possible if chronic urinary catheters or stents.  Also: Enterococcus, Candida. There were no significant differences detected for any of the secondary outcomes. 1. 3. 1. Data suggest that up to 15% of ICU patients treated with cefepime … 2) VRE – suspect especially if patient previously on vancomycin *Consider anti-Pseudomonal coverage if risk factors present. More frequent administration of a beta-lactam typically increases this amount of time. Mechanism: new macrocyclic antibiotic with narrow spectrum of activity against only C.diff (inhibits C.difficile RNA polymerases).Â. Used for: Drug of choice for MSSA infections (unless PCN sensitive, which is rare).  Good choice for cellulitis, osteomyelitis, endocarditis, and bacteremia from MSSA.Â. Ceftaroline (5th Gen Cephalosporin) – see Beta-lactam section above.  Covers MRSA, VISA, VRSA, Strep, Enterococcus faecalis/VRE (but not as good vs E.faecium).  Similar gram negative coverage as Ceftriaxone. S.aureus including MRSA, Streptococcus species (especially Group B strep in diabetics), N.gonorrhoeae (triad of pustular skin lesions, tenosynovitis, arthritis), Gram negative rods (Pseudomonas if IVDU). 66; Probably adequate: Piperacillin-tazobactam doesn't induce the production of AmpC beta-lactamases. Peyko V, Smalley S, Cohen H. Prospective Comparison of Acute Kidney Injury During Treatment With the Combination of Piperacillin-Tazobactam and Vancomycin Versus the Combination of Cefepime or Meropenem and Vancomycin.  Â, Achieves low serum concentrations (distributes widely into tissues) –, Main side effects = GI (nausea/vomiting/diarrhea) and elevated LFTs, Double coverage involves a beta-lactam plus either Fluoroquinolone or Aminoglycoside.  Use Aztreonam if PCN-allergic.Â. 2. All carbapenems are … 10-14 days Used for: prevention of recurrent UTI’s (as opposed to treatment of active infection). Mechanism: Lipopeptide antibiotic – forms transmembrane channels and depolarizes cells.  Rapidly cidal drug. Fidaxomicin (PO) Cefepime – main weakness is weak anaerobe coverage and no Enterococcus Zosyn (Piperacillin/Tazobactam) – broader due to excellent anaerobe coverage, activity vs Amp-susceptible Enterococcus. perforation, peritonitis, intraabdominal abscesses) – major anaerobic pathogen is Bacteroides species, Gynecological infections (endometritis, tuboovarian abscesses, pelvic inflammatory disease)– major pathogens include Prevotella species and others, Certain skin and soft tissue infections (Fournier’s gangrene, diabetic foot ulcer, decubitus ulcers, bite wounds) – anaerobic pathogens depend on site.Â, Classically best for infections “below the diaphragm” – mainly due to excellent activity vs Bacteroides, and less reliable activity vs Peptostreptococcus (gram positive oral anaerobe) and, Excellent (virtually 100%) bioavailability. Dicloxacillin is a reasonable oral choice for non-severe cellulitis; otherwise, Nafcillin tends to be better tolerated than Oxacillin (less hepatitis and rash), Note Zosyn’s higher dosing for PNA/Pseudomonas coverage: 4.5 g q6 hrs (vs. 3.375 g q6 for other indications). Used for: Uncomplicated urinary tract infections in women, especially in those with history of resistant bugs.  Given as a one-time mega-dose of 3 g (excreted into urine and achieves high levels there for several days.   Sometimes used for complicated UTI’s in males with resistant pathogens (3 g PO q3 days x several doses), although this is an off-label use. Spectrum: only covers Gram positives including MRSA, strep, and Enterococcus/VRE.  No gram negative activity. Aztreonam possesses greater convulsant properties than some cephalosporins, but much less than penicillin and cefazolin.46,47 In a series of 22 bacterial meningitis patients treated with …  No gram negative coverage.   Considered the gold standard for MRSA infections. Side effects: nausea, diarrhea, metallic taste, dose-dependent and possibly cumulative peripheral neuropathy (avoid multiple courses for recurrent C.diff), also Disulfiram effect w/ EtOH.  Peripheral neuropathy is usually reversible.Â, Avoid for long-term use due to potential pulmonary side effects: Hypersentivity Pneumonitis(occurs 7-10 days after therapy, usually resolves)  and, Contraindicated in renal failure with CrCl < 60 (poor excretion into urine). Itraconazole(PO or IV) Cefepime has been shown to be non-inferior to carbapenems. 6. "SUPER GRAM NEGATIVE ANTIBIOTICS" THAT COVER PSEUDOMONAS, VIII. C onsider for sepsis with gastrointestinal source - Cefepime can be use d for CNS infections and readily achieves therapeutic concentrations in the lungs . Similar to Zosyn, but Timentin has activity vs Stenotrophomonas, and is less effective vs Pseudomonas and Enterococci. Enter your email address below and we will send you your username, If the address matches an existing account you will receive an email with instructions to retrieve your username, Rebecca S. Pettit PharmD, MBA, BCPS, BCPPS, I have read and accept the Wiley Online Library Terms and Conditions of Use. Side Effects: photosensitivity, GI discomfort, teeth discoloration, inhibits bone growth in children, teratogenic, steatosis and hepatotoxicity. Remarkably non-toxic, but can rarely cause elevated LFTs, also GI upset (n/v), Poor penetration into urine – not used for UTIs.  Also, not much data on CSF penetration – not recommended for fungal meningitis.Â, Not well studied for Candida endocarditis (prefer Amphoterecin), All 3 agents are essentially interchangeable in terms of spectrum of activity. Cefepime Maxipime Moderate Increases Cephalosporins possess inherent anticoagulant properties and may increase bleeding risk Cefixime Suprax Moderate Increases Cephalosporins possess inherent anticoagulant properties and may increase bleeding risk Cefotaxime Claforan Moderate Increases Cephalosporins possess inherent anticoagulant … Main side effects: Hypersensitivity reactions including anaphylaxis, Rashes, Bone marrow suppression, Interstitial Nephritis,  GI (nausea, diarrhea, and C.diff) interstitial nephritis, GI (nausea, diarrhea, and C.diff), seizures (mainly with high doses in renal failure). Alternatives: Piperacillin/Tazobactam 4.5 g IV q6 hrs, Imipenem 500 mg IV q6 hrs or Meropenem 1 g IV q8 hrs E.coli is most common, followed by also other gram negatives (Proteus, Klebsiella, Serratia, Enterobacter) and  Staph saphrophyticus. *Role of anaerobes, even in nosocomial aspiration pneumonia, is unclear (but reasonable to add anaerobic coverage in that scenario). Used with beta-lactams against gram positive organisms for synergistic effect (mainly in endocarditis). (97%) vs. ceftriaxone and doxycycline (95%); moxifloxacin (90%) vs. ofloxacin plus metronidazole (91%); doxycycline plus metronidazole (91%) or ciprofloxacin plus tinidazole (96%); azithromycin alone (97%) or azithromycin plus metronidazole (96%) vs. metronidazole plus doxycycline plus cefoxitin plus probenecid *S.aureus if IV drug user, recent influenza. cefepime. Mullins et al 641 replacement therapies (RRT), time to resolution of AKI, pri-mary infection site, if sepsis type of sepsis (not indicative of primary site of infection), and SCr at day of hospital dis- Patients were included if they had a diagnosis of CF, age 30 days to 18 years, and received intravenous vancomycin, tobramycin, and piperacillin‐tazobactam or cefepime. Rifampin (PO and IV) Cefepime (C), a fourth generation cephalosporin, was found as effective and safe as ceftazidime in a previous randomized trial in our center (Kebudi R et al, Med Pediatr Oncol 36:434–441,2001). Dalbavancin (IV) - newer 2nd generation lipoglycopeptide antibiotic, with similar spectrum of vancomycin and indicated for skin and soft tissue infection. Noninferior (and likely superior) to oral vancomycin for initial treatment of C.difficile.Â, Aside from its role in mycobacterial infections, Rifampin’s other main use is its. While in the long-term group (time > 5 ds), there was no significant difference between P/T and cefepime therapy (OR = 1.06, p = 0.79) Asymmetry in Funnel B. Depends on clinical course (should continue at least until no more surgical debridement necessary and minimum of 10-14 days. 6) Stenotrophomonas maltophilia – nonlactose fermenting gram negative rod that causes infections, usually in ICU patients (esp with prior Carbapenem use) or immunocompromised. Used for: Upper respiratory infections, sinusitis, otitis media, cellulitis, Listeria infections, UTI’s, early Lyme disease (alternative to Doxycycline), and more. 66–69 3. Use the link below to share a full-text version of this article with your friends and colleagues. Spectrum: Broad spectrum vs Gram positives (including MRSA, E.faecium/VRE); Gram negatives but NOT Pseudomonas; Anaerobes, and unusual pathogens including spirochetes, Rickettsia, Erhlichia, Coxiella, Typhoid/Paratyphoid Salmonella. The second component of these regimens is typically either piperacillin-tazobactam (pip-tazo, brand name Zosyn) or cefepime (brand name Maxipime), which adds broad-spectrum Gram negative … 1. Cefepime 1 g IV q12 hrs (especially if prior resistant organisms or Pseudomonas), Complicated UTI (defined by presence of anatomic or functional abnormality in GU tract, or urinary catheter). *If nosocomial – treat as HAP, with preference for Piperacillin/Tazobactam, Imipenem or Meropenem for anaerobic coverage, or add Clindamycin or Metronidazole. Spectrum: Excellent activity vs. Anaerobes and Gram positive cocci – Strep and Staph, including ~ 50% of community-acquired MRSA, but NOT Enterococci.       If you do not receive an email within 10 minutes, your email address may not be registered, Mechanism: Oxazolidinone class –unique ribosomal inhibitor (acts on 50S subunit).  Bacteriostatic agent. Cefepime 1-2 g IV q8h (preferred regimen if S. pneumoniae is also considered likely) OR Meropenem 1 gm IV q8h (only if known to be colonized with ESBL organism or multidrug resistant pathogen such as Pseudomonas or Acinetobacter) OR Severe penicillin allergy: aztreonam 2 g IV q8h PLUS Levofloxacin 750 mg IV q24h OR gentamicin 7 mg/kg/dose IV daily PLUS … Spectrum: “Respiratory Fluoroquinolone” -  excellent activity vs. Strep pneumo, slightly less reliable Pseudomonas coverage than Cipro. Long-term efficacy is unclear. classification: edematous vs. necrotizing pancreatitis. Cefepime, ceftazidime, ciprofloxacin PLUS Metronidazole Ceftriaxone, cefotaxime, cefepime, ceftazidime PLUS Metronidazole OR Gentamicin or tobramycin PLUS Metronidazole or clindamycin ± Ampicillin Healthcare-associated intra-abdominal infection includes a spectrum of adult patients who have close association with acute care hospitals or reside in chronic care …   Lacks good anaerobic coverage. Oral anaerobes, enteric gram negative rods, S.aureus, Streptococcus species. Ofted used as 2nd agent of “double coverage” when suspecting serious Pseudomonas infection (including for HAP/HCAP/VAP), Side effects = ATN/nephrotoxicity (manifests after 3-5 days, usually reversible) and oto/vestibular toxicity (irreversible, unlike Vancomycin).   If using long-term, check baseline audiology test and ~q2 weeks.Â, Three ways to dose aminoglycosides (doses listed for Gentamicin). A large survey of more than 2,000 patients treated with cefepime reported only three cases of seizures, and these were found to be unrelated to antibiotic administration.45. Thrombocytopenia is a serious hematological finding with a reported incidence ranging from 15–58% in intensive care unit (ICU) patients [].A platelet count nadir below 100,000/µL and a decrease in platelet count of ≥ 30% has been associated with higher mortality in this patient population [].Although this condition is commonly encountered in clinical practice, diagnosis remains a challenge. Negative gram stain – Vancomycin + Ceftriaxone, or Vancomycin + Cefepime or Ceftazidime if risk factors for Pseudomonas. + Cefepime* 2 g IV q8h If non-life threatening penicillin or cephalosporin allergy: Substitute meropenem* 2 g IV q8h for cefepime If life threatening penicillin allergy: Substitute aztreonam* 2 g IV q6h for cefepime neurosurgery Aerobic gram-e.g.,) S. aureus Coag-negative Staphylococci 1st line: *Add Vancomycin if: Hypotensive or severely ill, pneumonia, suspected catheter-related infection, known colonization with MRSA or PCN-resistant Strep, recent prophylaxis with fluoroquinolones. are a common cause of nosocomial pneumonia and treatment can be complicated by AmpC resistance.  Anti-pseudomonal PCNs - Piperacillin, Ticarcillin Additionally, the combination of cefepime fluoroquinolones resulted in … Empiric antimicrobial therapy for healthcare-acquired infections often includes vancomycin plus an anti-pseudomonal beta-lactam (AP-BL). Cefepime answers are found in the Johns Hopkins ABX Guide powered by Unbound Medicine. If severe or healthcare-associated infection, consider Piperacillin/Tazobactam or Imipenem or Meropenem. It might be an attractive option in an environment of increasing resistance among gram-negative bacteria. We evaluated the efficacy of non-carbapenems vs. carbapenems in 'ESCPM' bacteraemia. Infections arising from the oral cavity (Dental abscesses, Peritonsillar abscess, Deep neck space infections) – major pathogens include Peptostreptococcus, microaerophilic streptococci, Fusobacterium, and others. Associated conditions include diabetes, neuropathy, vascular disease: Common pathogens: Mild disease: Ciprofloxacin 750mg PO q12h (+/- rifampin 600mg PO qd) OR: Levofloxacin 750 mg PO qd (+/- rifampin 600mg PO qd for S. aureus if present) OR: Augmentin … AKI was identified in 54.5% (18/33) of patients receiving piperacillin‐tazobactam and 13.2% (5/38) of patients receiving cefepime (P ≤ 0.0001). 1. Spectrum: Active mainly against Gram negative organisms including Pseudomonas, Klebsiella, Enterobacter, Acinetobacter.  No activity vs Gram positives.  Limited activity vs anaerobes.  Proteus and Serratia are generally resistant. Resistance develops rapidly – not suitable for sustained therapy for severe infections.  1) Atypical infections – Legionella, Chlamydia, Mycoplasma.  Vanc/Zosyn is not adequate for Community-Acquired Pneumonia. “Extended Infusion” strategy – 3.375 g over 4 hours, q8 hrs – some data suggesting better outcomes for treatment of Pseudomonas infections compared to standard dosing (goal to maximize time above MIC). Can be given in aerosolized form as well as IV (both forms used quite commonly in Cystic Fibrosis patients with resistant gram negative infections), Old drugs that had been long abandoned for routine use due to its toxicity Ã, CNS abscesses (Brain, epidural, subdural). More patients in the piperacillin-tazobactam group had immune compromise (27.1% vs 20.9%) but had a shorter time to receipt … Microbiologic success is dependent on pharmacokinetic and pharmacodynamic parameters and the organism’s MIC.8 As previously mentioned, the pharmacodynamic target for beta-lactam antibiotics is the time the drug concentration remains above the MIC of the infecting organism. Aztreonam – high rates of resistance at most institutions, so use only if PCN-allergic, and empirically double-cover. Drug of choice for many severe fungal infections: Zygomycetes, Cryptococcal Meningitis (induction phase with flucytosine), Severe Histoplasmosis/Blastomycosis/Coccidioidomycosis Cidal for many molds à drug of choice for Invasive Aspergillosis! Advantage over Posaconazole is that it has IV formulation as well as PO, so more suitable for initial therapy of acute infection. All fluoroquinolones have atypical coverage (but Cipro – relatively weaker against Chlamydia and Mycoplasma, but good vs Legionella).

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