Miscellaneous
This free iTunes segment is just one tiny snippet of the fully-loaded 3-hour monthly Peds RAP show. Earn CME on your commute while getting the latest practice-changing peds information: journal article breakdowns, evidence-based topic reviews, critical guideline updates, conversations with experts, and so much more. Sign up for the full show at hippoed.com/PEDSRAPPOD. Pediatric ID specialist Michael Neely, MD, and Michael Cosimini, MD discuss how cephalosporins work and which bugs they do and do not kill. Pearls: In general, cephalosporins do not cover anaerobes, enterococcus, listeria and MRSA. Oral cephalosporins are generally not first line in pediatrics. Some exceptions include the treatment of UTIs and some skin and soft tissue infections; group A strep and sinopulmonary infections in penicillin allergic patients are other common indications. 1st generation cephalosporins do have gram positive coverage, but do not work well against strep pneumo, MRSA, enterococcus. They do cover some enteric gram negative bacteria, the “PECK” organisms. What are cephalosporin antibiotics and how do they compare to penicillins? Chemically, both penicillins and cephalosporins are beta-lactam antibiotics, with the beta-lactam portion responsible for bacterial killing. The chemical portions off the beta-lactam ring make the antibiotics different. Beta-lactam antibiotics work by binding to the penicillin-binding protein on the bacterial cell wall. These proteins have structural functions that maintain the integrity of the bacterial cell wall and therefore, when these antibiotics bind, the penicillin-binding protein is disrupted, the cell wall falls apart and the bacterial dies. How do you keep a straight spectrum of activity for antibiotics? To help with this, think of bacteria into big categories: gram-positive, gram-negative and “other”. Gram-positive bacteria include: Staph aureus (MSSA, MRSA), Streptococcus (Group A Strep, Group B Strep, Strep pyogenes, Strep viridans), Enterococcus, Pneumococcus, Listeria Gram-negative bacteria are a much bigger group and can be divided into: Respiratory gram-negatives include Moraxella, Haemophilus, Meningococcus Enteric gram-negatives include the “PECK” bacteria: Proteus, E.coli, Klebsiella What bacteria do cephalosporins not cover? In general, cephalosporins do not cover anaerobic bacteria, enterococcus, listeria and MRSA. There are a few exceptions to this rule. Cefoxitin (a second generation cephalosporin), for example, does have anaerobic coverage. It is commonly used in the treatment of PID as it covers enteric anaerobes and Neisseria gonorrhea. There is a 5th generation cephalosporin that does cover MRSA (discussed later). Are cephalosporins well absorbed? Generally speaking, cephalosporins in oral formulations are not as well absorbed as penicillins and are more difficult to get where they need to go outside the urinary tract. Also, generally speaking, no beta-lactam really gets into the spinal fluid in very high concentrations; all of them do have better penetration when there is inflammation. Practically, remember that the penetration into the CSF between ampicillin and ceftriaxone is negligible. What bacteria do first generation cephalosporins cover? Although the classic teaching is that cephalosporins are good for gram-positive coverage (staph and strep), this is not a hard and fast rule. As stated, enterococcus is not covered by any cephalosporin and MRSA is not covered by most cephalosporins. First generation cephalosporins are also good for coverage of the “PECK” enteric gram negative bacteria, but not good for coverage of other gram negative bacteria. These organisms tend to cause UTIs and therefore, first generation cephalosporins (for example, cephalexin) are frequently used for UTI treatment. Of course, resistance can occur. Even though strep pneumo is a gram-positive organism, when it comes to first generation cephalosporins, it acts like a gram-negative organism and therefore, first generation cephalosporins do not work well against strep pneumo. What about bacteria that develop resistance? A patient with an E. Coli UTI, for example, may have a microbiology laboratory report stating that the E. Coli is resistant to a first generation cephalosporin but the patient is still getting better. This may have to do with the type of infection the patient had; for example, a healthy patient with a simple cystitis may have been able to stay well hydrated and the normal immune system was able to clear the E. Coli. This question can also be answered in the context of breakpoints, that is when the bacteria become susceptible or resistant to the antibiotic depending on the site of infection. Some labs will actually label a bacteria resistant or susceptible depending on whether the infection is in the urine, spinal fluid or blood. Therefore, if a lab that reports site-specific breakpoints suggests that an E. Coli is resistant to a first generation cephalosporin in the urine, the lab has already taken into account the higher concentration of drug in the urine. Similarly, a pneumococcal isolate that may be resistant to ceftriaxone in the CNS may be susceptible to ceftriaxone as a pneumonia because there are much higher concentrations of ceftriaxone in the lungs than in the spinal fluid. When should a skin or soft tissue infection be treated with a first-generation cephalosporin? When should MRSA be suspected? This can be a tricky question as an outpatient, but there are some clues to gauge whether or not the infection may be caused by MRSA. One, it is helpful to know the community prevalence of MRSA. In some communities, community acquired staph aureus infections are up to 80-90% MRSA. In these communities, MRSA coverage should of course be given. If the prevalence is much lower, using a first generation cephalosporin, such as cephalexin may be reasonable. Other clues can be more specific to the patient the their families. Is the patient or family known to be colonized with MRSA? Have they had an MRSA infection in the past? If MRSA coverage is needed, either trimethoprim-sulfa or clindamycin generally is a good approach. A randomized controlled trial published in the NEJM showed no difference in outcomes when treating a known MRSA infection. Miller LG et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015 Mar 19;372(12): 1093-103. https://www.ncbi.nlm.nih.gov/pubmed/25785967 In general, the quality of the infection does not help point to MRSA or not. There is some suggestion that if there is a soft-tissue abscess this is more likely staph aureus and if there is just pure erythema, tenderness and warmth without abscess, this is more likely to be Group A strep. Remember, no matter what antibiotic is started for cellulitis (or any infection, for that matter), follow up is essential. If you are on the right antibiotics, cellulitis should be improving within 24 hours.