Penicillin Allergy

Administration of a cephalosporin to a patient with a history of penicillin allergy

More than 99 percent of penicillin skin test-positive patients tolerate treatment with carbapenems, despite a significant rate of cross-reactivity between penicillins and carbapenems on skin testing.

An individual patient's risk of reacting to a carbapenem may be assessed based upon the results of penicillin skin testing, the clinical features of the penicillin reaction, and the time elapsed since the last reaction to penicillin. The approach is identical to that for cephalosporins.

Aztreonam is the only monobactam currently available for clinical use. There is no evidence of immunologic cross-reactivity between penicillins and monobactams, and penicillin-allergic patients may receive aztreonam normally.

INfective Endocarditis: Acute

So today I got one pt with IE..so lets discuss lil bit abt IE management:

Treatment:
Empiric treatment:

• for native valve endocarditis: Pen G+ genta--for synergistic coverage for strep
• for prosthetic valve: have to cover MRSA and Coag negative Staph aureus : so have to use Vanco+genta
• For IVDA: have to cover staph aureus: Nafcillin/vanco+ Genta
• rifampin can be added if pt has any foreign body: like prosthetic valve..as Rifampin can penetrate biofilm  of most of the pathogen ...shoud be added to Vanco+gentaan 
• can use Linezolid in place of vanco if renal function is not good and have difficulty in achieving trough level.
• if vanco resistance: then can use linezolid or Daptomycin
• have to give ABX for almost 4-6 weeks and Only IV  treatment not oral ..Oral should be used only as suppressive for inoprable Prosthetic valve Endocarditis.
• 
  

If pt has vagetation then it is difficult to eradicate oragnism as antibiotic had dofficulty in penetrating fibrin/platelet rich thrombi

specific Treatment:
Usually Native valve endocariditis is caused by Strep Viridans and Bovis : can use
-Pen G alone If no other complication but require Continous IV infusion 12-18u/day or 6times a day for 4 weeks  so has very poor pt compliance
- or ampicillin 12 gm/day as continous IV infusion or 6 equally divided doses iv
- can Use ceftriaxone in place of Pen G, and it requires only twice a day dose   for sick and Once a day dose for Stable pt  so has good pt compliance..sometimes can be given IM if IV access is difficult.
-cefazolin 6gm/day can be also used in 3 equally divided doses for 4 weeks
-if allergic to penicillin ; use vanco 30 mg/kg/day , but not more then 2gm/day q12hrly for 4 weeks
-for sick/complicated pt ahve to use 2 drugs so have to add genta 1 mg/kg with Pen G or Ceftriaxone


For enterococcal Infection:
same treatment can be used
if PVE: then 6 weeks of treatment is used
-A combination of an inhibitor of cell wall synthesis (ie, penicillin, vancomycin) with an aminoglycoside (ie, gentamicin, streptomycin) is necessary to achieve bactericidal activity against the enterococci. Tobramycin or amikacin does not act synergistically with antibiotics active against the bacterial cell wall.
-if resistnace to Beta lactmase then : use Ampi-sulbactam/vanco/cipro/imipenam  +  genta




For VRE:

• can use Quinupristin/dalfopristin
• ampi+ceftriaxone
• ampi+ imipenam
• linezolid
• chloramphenical

For MSSA:

• Nafcillin/oxacillin 2gm/day q4hrly
• cefazolin 2gm IV q 8hrly
• if allergic to pen: use Vanco 30 mg.kg /day

Id staph with MIC for vanco> 1.5-2 mcg/ml ---use other ABX---linezolid/daptomycin

If PVE +MSSA:

use Cefazolin/nafcillin/oxacillin for 4-6 week

add Genta+ rifampicin for 2 week

PVE+MRSA:

use Vanco+ genta+rifampin

Linezolid had better outcome then Vanco: but have to monitor blood count

or daptomycin

HACEK:

use ampicillin or cefazolin

VAlve replacement Surgery:

if IE cause

• CHF
• >1cm vegetation
• perivalvular or myocardial abscess
• valve dysfunction
• >1 embolic episode

Fungal IE:

Surgical excision+ Amphotericin B

Daptomycin

Recently we discussed New drug Daptomycin...so I m Gonna post few facts regarding it:

MOA: cause Cell wall depolarization--> inhibit DNA, RNA and Protein synthrsis

Organism suscetibility: only gm +ve cocci--> staph-->MRSA too, Strep, ENterococci --also GRE

Used for MRSA, Rt sided endocarditis, soft tissue Infection...

Side effect:
Renal Failure
rhabdomyolysis---> so be careful while using dapto and statin together.

Limitation:
Cant be used in Pneumonia as It binds to surfactant ..

conjuctivits

pseudomonas infection

Antimicrobial agents are needed to treat Pseudomonas infections. Two antipseudomonal drug combination therapy (eg, a beta-lactam antibiotic with an aminoglycoside) is usually recommended for the initial empiric treatment of a pseudomonal infection, especially for patients with neutropenia, bacteremia, sepsis, severe upper respiratory infections (URIs), or abscess formation. The choice of antibiotic also depends on the site and extent of infection and on local resistance patterns.^[5] Reports of more resistant strains of Pseudomonas organisms to the currently used antimicrobials are causing much concern.

B cepacia has grown resistant to aminoglycosides, antipseudomonal penicillins, and most beta-lactam agents. Some strains are variably susceptible to third-generation cephalosporins, ciprofloxacin, trimethoprim-sulfamethoxazole, ampicillin-sulbactam, chloramphenicol, or meropenem.

Because human cases of glanders are rare, limited information is available about antibiotic treatment of the organism in humans. Sulfadiazine has been effective in experimental treatments of animals and humans. B malleiorganisms are usually sensitive to tetracyclines, ciprofloxacin, streptomycin, novobiocin, gentamicin, imipenem, ceftazidime, and sulfonamides. Resistance to chloramphenicol has been reported. Treatment duration is often prolonged, from 1-2 months, often combined with surgical drainage.

Ceftazidime alone or in combination with either trimethoprim-sulfamethoxazole or amoxicillin clavulanate is the therapy of choice for B pseudomallei. The organism is usually sensitive to imipenem, penicillin, doxycycline, azlocillin, ceftazidime, ticarcillin-clavulanic acid, and ceftriaxone. Initiate treatment early in the course of the disease. The organism is resistant to ciprofloxacin and aztreonam. Treatment is often prolonged, from 3-12 months, with the longest duration of therapy used for chronic extrapulmonary disease.

Pseudomonas vaccines are also currently used to reduce infection risks in patients with cystic fibrosis (CF) and are still under investigation.Pseudomonas aeruginosa infections include the following:

• Bacteremia
  

  • Empiric antibiotics are often started before the organism is identified.
  • Whether single-drug or combination therapy is most effective in patients who have bacteremia and neutropenia is debated. The author is unaware of any prospective randomized comparison between monotherapy and combination drug therapy for patients with pseudomonal bacteremia. Duration of treatment is at least 2 weeks.
• Bone and skin infections
  

  • A 4-week course of aminoglycoside antibiotics is often successful for managing vertebral osteomyelitis.
  • Sternoarticular pyarthrosis has been managed effectively with aminoglycoside and antipseudomonal penicillin if administered for at least 6 weeks.
  • Patients with osteomyelitis of the pubic symphysis require treatment for at least 4 weeks with an antipseudomonal penicillin and aminoglycoside combination. Surgical intervention is not usually indicated.
  • Patients with osteochondritis require medical and surgical treatment. Parenteral administration of 1-2 antipseudomonal agents is recommended before surgical debridement. The recommended regimen continues postsurgical treatment for 1-2 additional weeks with oral (PO) ciprofloxacin.
  • Chronic contiguous pseudomonal osteomyelitis requires 4-6 weeks of combination therapy, in addition to surgical debridement.
  • Burn wound sepsis management requires early intervention with daily wound inspection and systemic antibiotic combination regimens. Monotherapy is not indicated.
  • Management of pseudomonal cellulitis includes the use of PO antibiotic for 7-10 days; this often resolves a localized infection.
  • Pseudomonal toe web infections require initial debridement with applications of silver nitrate or 5% acetic acid to the toe webs and the dorsal and planter areas. Following this initial treatment, apply a topical antibiotic, silver sulfadiazine cream, or Castellani paint until infection resolves. PO quinolone effectively reduces the duration of infection.
  • Pseudomonal folliculitis is often self-limited; treatment may require only application of silver sulfadiazine cream or 5% acetic acid wet compresses for 20 minutes 2-4 times daily with topical antibiotics.
• CNS infections
  

  • Ceftazidime, cefepime, or meropenem are the antibiotics of choice because of their high CNS penetration. Initially, consider double coverage with an aminoglycoside for patients with adequate renal function. Aztreonam, ciprofloxacin, or levofloxacin are indicated for patients with renal failure and those allergic to beta-lactam. Imipenem-cilastatin should be avoided because of the risk of seizures. Intrathecal treatment should also be considered. Treatment duration should be at least 2 weeks.
  • Antibiotics can be used in the initial treatment of brain abscesses that are multiple, small (ie, < 2 cm), poorly distributed, or relatively difficult to access. Antibiotic therapy duration depends on the speed of abscess shrinkage, but therapy usually lasts 2-6 weeks.
• Ear and eye infections
  

  • Otitis media in at-risk populations should be treated with antipseudomonal agents for at least 10 days.
  • Chronic suppurative otitis media requires daily aural toilet and treatment with antibiotics (eg, ceftazidime, mezlocillin, ciprofloxacin), and often surgical treatment.
  • Otitis externa can be treated with local care using an acetic acid compress and daily aural cleaning.
  • Management of malignant externa otitis should be aggressive and involve both medical and surgical therapies. The conventional therapy (ie, an aminoglycoside and a beta-lactam agent with antipseudomonal activity) is needed for at least 4 weeks to treat localized infections and 6-8 weeks or longer to treat extensive disease. Monotherapy using ceftazidime intravenously (IV), cefepime IV, or ciprofloxacin PO for 6 weeks has been reported effective.
  • If gram-negative rods are isolated from the Gram stain of an eye infection, immediately start a combined topical and subconjunctival (or subtenon) therapy of aminoglycoside antibiotics. Aminoglycoside solution (not ointment) must be applied to the affected eye every 30-60 minutes. Subconjunctival therapy is needed for the first 3 days of treatment. Total duration of therapy is at least 1 week. An alternative therapy uses a quinolone antibiotic solution. The addition of parental or PO antipseudomonal antibiotics also has been beneficial.
  • Pseudomonal endophthalmitis requires immediate antibiotic therapy, using aminoglycoside and antipseudomonal penicillin administered via a parenteral and subconjunctival, topical, or intraocular route. Therapy duration depends on the clinical improvement.
• GI and GU infections
  

  • Treat GI manifestations of pseudomonal infection with antibiotic therapy for patients with severe localized or systemic infections.
  • The treatment modality for urinary tract infection (UTI) depends on the presence of sepsis, degree of chronicity, potential sites of persistent infection, and local antibiotic susceptibility. Ideally, indwelling urinary catheters should be removed. If the catheter cannot be removed, consider treating only symptomatic episodes or exacerbations because it is not feasible to totally eradicate the organism. Aminoglycosides and quinolones remain the agents of choice.
• Cardiovascular (CV) and respiratory infections
  

  • To treat endocarditis, administer an antipseudomonal beta-lactam with high-dose aminoglycoside for approximately 6 weeks.
  • According to the criteria used in France to select antibiotics to treat VAP, the following 2 risk factors must be considered: (1) administration of broad-spectrum antibiotics in the previous 15 days and (2) mechanical ventilation for fewer than 7 days or for 7 or more days. The extended factors predict the involvement of multiresistant nosocomial P aeruginosa, suggesting administration of carbapenems to those who have undergone mechanical ventilation of 7 or more days and who have been exposed to antibiotics in the prior 15 days.
  • The role of antibiotic prophylaxis or chronic suppression of respiratory pseudomonal infections in patients with CF is controversial. Among the promising treatment plans are intermittent aerosolization of antibiotics to patients with CF who have established pseudomonal lung infections.
  • Choices for empiric antibiotic treatment in patients with a history of Pseudomonas infection requires review of previous culture sensitivity.
  • More widely accepted is the treatment of children with pseudomonal infections by using fluoroquinolone, especially children with previous therapeutic failure or resistance to multiple other antibiotics.^[6] Treatment often continues until symptoms resolve (ie, 1-2 wk).
  • Inhalation of mucolytic and hydrating agents, postural drainage, and chest physiotherapy often are therapies used together. Bronchial lavage also has been used to remove respiratory secretions.

ESBL

Extended-spectrum ß-Lactamases (ESBLs) are extremely broad spectrum ß-Lactamase enzymes found in a variety ofEnterobacteriaceae. Most strains producing these ß-Lactamases are Klebsiella pneumoniae, other Klebsiella species (i.e., K. oxytoca), and Escherichia coli. When producing these enzymes, organisms become highly effective at inactivating various ß-Lactam antibiotics.


 these organisms are resistant to all ß-Lactam antibiotics except cephamycins (cefoxitin, cefotetan) and carbapenems. In addition, ESBL-producing organisms are frequently resistant to many other classes of antibiotics, including aminoglycosides and fluoroquinolones.^[2-4]Hence, a more appropriate name would be "multidrug resistant organisms."


The initial approach to assessing the presence of ESBL isolates in an institution should involve examining the susceptibility of K. pneumoniae and E. coli to ceftazidime. If susceptibilities to ceftazidime are less than 100%, ESBL-producing organisms are probably present. 

Conclusions

The ESBL-producing organisms are a breed of multidrug-resistant pathogens that are increasing rapidly and becoming a major problem in the area of infectious diseases. High rates of third-generation cephalosporin use have been impli-cated as a major cause of this problem. Problems associated with ESBLs include multidrug resistance, difficulty in detection and treatment, and increased mortality. Of all available anti-microbial agents, carbapenems are the most active and reliable treatment options for infections caused by ESBL isolates. However, overuse of carbapenems may lead to resistance of other gram-negative organisms. Therefore, restricting the use of third-generation cephalo-sporins, along with implementation of infection control measures, are the most effective means of con-trolling and decreasing the spread of ESBL isolates.