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Serratia UTI discussion

If you got here without taking the case quiz go back here Dysuria and fever post surgery and take it.

My Recommendation

Change to ertapenem. He will need at least 14 days of therapy and without established effective oral options it will need to be completed intravenously. In future, fosfomycin may be shown to be a good option. See below.

Why not stay on ceftriaxone?

He appears to be responding to ceftriaxone but this may be short lived. The susceptibility test did not report ceftriaxone. However the asterix next to cefazolin denotes that there is more information available if it is “clicked” on. This is what is visible after “clicking”:

“This organism has a chromosomal Inducible Beta lactamase. The organism is resistant to ampicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam, and all cephalosporins.”

Serratia marcescens is a member of the so-called “SPICE” group of organisms (Serratia, Pseudomonas, Proteus, Citrobacter, Enterobacter) that all produce AmpC beta-lactamases. They are also referred to as inducible beta-lactamase producers (IBLs).

This is not an optimal means of reporting susceptibilities that will be rectified in upcoming improvements to the Cerner EMR.

Why not gentamicin or tobramycin?

Aminoglycosides are too toxic for use in this setting where other options are available. They are particularly worrisome in the elderly where renal function is often reduced.

Why not nitrofurantoin?

Nitrofurantoin is only indicated for simple cystitis in women. This man has either pyelonephritis or prostatitis.

Why not fosfomycin?

Fosfomycin is an old agent that has been “resurrected”. It’s only officially indicated as single dose therapy for simple cystitis in women. However, there is considerable interest in evaluating its role in other infections including prostatitis. See this recent paper from Clinical Infectious Diseases suggesting it may be of utility.

AmpC E. coli UTI Review

If you got here without taking the case quiz go back here AmpC E. coli UTI case and take it

My recommendation

Imipenem. Carbapenems are reliable therapy for AmpC E. coli pyelonephritis. Commonly used beta-lactams (ceftriaxone and piperacillin/tazobactam) are not. Read more about carbapenems here Carbapenem notes.

Why not nitrofurantoin?

This woman has pyelonephritis as evidenced by her systemic symptoms. Nitrofurantoin in only indicated for thetreatment of cystitis, not pyelonephritis.

Why not tobramycin?

Tobramycin would be effective therapy for this infection but is considerably more toxic than is imipenem. Close monitoring of drug levels improves safety but nephrotoxicity, ototoxicity and vestibulotoxicity are common.

Why not ertapenem?

Ertapenem is a newer, once daily carbapenem that would be effective therapy in this case. Currently it is reserved for use in outpatient settings in British Columbia though that is being reconsidered.

Why not fosfomycin?

Fosfomycin is an old antibiotic making a comeback and its only approved indication is for the therapy of simple cystitis in a 3 gram single dose form. However, it is one of the only oral options for resistant organisms like in this case and experience with its use for pyelonephritis and other indications is growing.

Take home

This case is a great example of the relentless progression of antibiotic resistance and the need to be very careful with the remaining effective antibiotics. E. coli is present in large numbers in all people. It is the most common cause of urinary tract infections and, until recently, was relatively easy to treat with several reliable oral antibiotic options. These AmpC strains of E. coli are challenging. If you are interested in more in-depth treatment of AmpC beta-lactamases look here Clin. Micro. Rev – Beta Lactamases.

The scenario presented here is now a regular occurence in BC. The use of carbapenems is increasing and with it the worry of promoting and sustaining carbapenem-resistant organisms (CPOs) for which there are almost no antibiotic options. This makes efforts at prevention of urinary tract infections more important than ever. Attention to hydration and catheter use in hospitals and long term care are particularly important.

Red Arm 1 Review

If you got here without taking the case quiz go back here Case Quiz Red Arm 1 and take it.

What did I suggest?

I suggested that discontinuing antibiotics was appropriate.

Why?

It didn’t make sense that this was a non-responding cellulitis of his arm. He had also had some cefuroxime in the ICU (not sure of the indication) and this developed while on it. The “look” isn’t typical of cellulitis and the distribution is very suspicious for a response to extravasation of some infusion he received in ICU.

What happened?

Antibiotics were discontinued and it resolved over the next several days.

Take home

Not all acute inflamed areas of skin are cellulitis.

Red leg 1

What did I recommend?

I suggested that continuing with ceftriaxone was appropriate.

Why?

Despite the reports of it not improving, the overall look of this leg is of one that is improving. Bad cellulitis takes quite a long time to resolve and often the extent of the redness gets larger initially despite totally appropriate therapy. His leg is red but not BRIGHT red. You really need to look at a lot of cellulitic limbs through the course of their therapy to get a good feel for this.

The most important assessment is whether or not there was prompt improvement in systemic signs of infection after initiation of therapy. When this man was asked how he felt, in the overall sense, compared to when he first presented he responded “200% better!”. His fever had resolved, his appetite had improved and apart from a very uncomfortable leg he felt close to normal. I was convinced that he was responding well.

Why not go back to cefazolin?

A strong argument could be made for this as Group A Streptococci and S. aureus are well treated with cefazolin and it avoids the promotion of resistance in Gram- negative bacilli (in particular E. coli) by ceftriaxone. However, he appeared to be near ready for discharge and ceftriaxone facilitates home IV or OPAT therapy. Granted, cefazolin plus probenecid would be another option. I would not fault anyone for recommending going back to cefazolin.

What happened?

At the start…

]1 Click image for larger version

Four days later…

He was changed to oral therapy.

And 7 more days later (2 days after stopping antibiotics)…

Carbapenem Case 1 review

What I recommend

Change to Ceftriaxone and metronidazole.

This is a case of “Mild to Moderate”” diverticulitis. Carbapenems are almost never empirically indicated for diverticular disease and the first choice for “Severe” diverticulitis is piperacillin-tazobactam. Have a look at these therapy recommendations for diverticulitis.

In general, carbapenems should not be the first therapy for intra-abdominal infections that arise outside of hospital. It is useful to frame the choices of empiric therapy for intra-abdominal infections into 4 accending choices:

  1. Cefazolin/metronidazole (met/cef) This is the therapy of choice for uncomplicated infections such as appendicitis in otherwise healthy people that have not been recently hospitalized.

  2. Ceftriaxone/metronidazole The “step up” from met/cef that is appropriate for uncomplicated but more serious infections in people with underlying medical conditions.

  3. Piperacillin/tazobactam Appropriate initial empiric therapy for people with complicated intra-abdominal infections especially those that have recently been in hospital where the likelihood of colonization with more resistant organisms is higher.

  4. Imipenem Generally not indicated as empirical therapy. The exception is for people that have had recent infections caused by microbiologically proven resistant organisms.

More general information about carbapenems can be found here Carbapenem Notes

Dysuria in men

These are the responses and a discussion of a case quiz – Dysuria in men.

If you reached this page without taking the case quiz feel free to click on the link and make your selection. You will be redirected back to this page.

UTIs in men

The convention of calling all UTIs in men “complicated” is simplistic but does signify the need to think differently about the diagnosis and therapy in men vs. women. Cystitis is women is the most common form of UTI and often very easily treated. “Cystitis” in men is very often accompanied by acute prostatitis that is difficult to diagnose and difficult to treat. If acute prostatitis progresses to chronic prostatitis it becomes one of the most difficult-to-treat conditions known. For this reason I believe that it is safer to assume prostatitis is always present.

Of the available choices I believe that either TMP/SMX or ciprofloxacin for 3 weeks are most appropriate. Both agents achieve excellent levels in prostate and are “tried and true” for this indication. A three week prescribed course is likely to achieve about a 2 week average course with compliance in men being less than perfect. In the practical sense, if follow-up is assured, a short course could be prescribed that would allow for the completion of culture and susceptibility with specific therapy then prescribed to complete the course.

Men don’t get cystitis, they get prostatitis.

Cystitis in women of child-bearing age

These are the responses and a discussion of this case quiz – Dysuria in an adult woman

If you reached this page without taking the case quiz feel free to click on the link and make your selection. You will be redirected back to this page.

Dysuria and frequency resulting from acute cystitis in women of child-bearing age is a very common reason for primary care visit. This type of urinary tract infection (UTI) is commonly referred to as “uncomplicated” to distinguish it from all other types of UTIs that all get the designation “complicated”. I can’t think of a more stupid classification system. But more on that in other posts…

One would think that this common, easily diagnosed condition would be managed very similarly by all physicians. It isn’t. There is large variance in history taking, physical examination practices, selection of laboratory tests, interpretation of laboratory tests, selection of empiric antibiotic and duration of therapy.

An office visit for this complaint should not take long but there are important elements to consider.

History

One very important distinction is between cystitis alone and cystitis accompanied by pyelonephritis. Questions aimed at differentiation might include “Have you had a fever and if so have you measured it?” “Have you had any pain in your back?” People with pyelonephritis are generally systemically unwell whereas people with cystitis are not.

Another consideration is the possibility of urethritis causing dysuria and frequency. Questions aimed at determining the possibility of STIs may be indicated.

Pregnancy is important to rule out as management is different in pregnancy.

Physical Exam

Exam should be limited in most cases of acute cystitis. Measurement of temperature is always prudent and it is good practice to instruct office staff to take the temperature of patients with potential infection-related symptoms when placing them in the examining room.

Always look for costo-vertebral angle tenderness by gentle tapping with the closed fist. Pelvic exam should be reserved for those in which there is considerable suspicion of STI.

Laboratory

A dipstick urinalysis (or other laboratory performed urinalysis if quickly available) is always indicated. A negative urinalysis should increase the suspicion of urethritis potentially caused by STI. Leukocytes, blood and nitrites are the analytes of interest. Inflammation is associated with leukocytes, while nitrites are present if there are bacteria from the family Enterobacteriaciae present. As E. coli is, by far, the most common bacterium causing UTI, many UTIs are manifest by nitrites present on urinalysis. However, other organisms (most notably Enterococci) can cause UTI and do not reduce nitrates to nitrites and therefore the nitrite test will be negative.

There is no broad consensus concerning the advisability of urine culture in this setting. Many experts (like me) believe that, because empiric therapy is indicated and effective in the large majority of patients, culture is not indicated. Culture is relatively expensive the the result is quite unlikely to influence the care. All people who fail empiric therapy should have cultures, of course.

Nitrofurantoin is now preferred empiric therapy

Recently, in part because of increases in resistance rates to trimethoprim-sulfamethoxazole and fluoroquinolones, and in part to reserve fluoroquinolones and cephalosporins for more serious hospital-associated infections, nitrofurantoin has become the Drug of Choice. Though slightly more expensive, the monohydrate/macrocrystals formulation (Macrobid TM) is preferable as it is dosed 100 mg BID. The other available form (Macrodantin TM) is macrocrystals only is dosed 50-100 mg QID. Specify Macrobid when prescribing. Duration of therapy is 5 days for either formulation.

Despite being used for many years, resistance is still rare in E. coli and many strains of enterococci are also susceptible. It cannot be used for pyelonephritis and caution must be used in patients with renal dysfunction. See http://infectionnet.org/questions/nitrofurantoin-safety-in-the-elderly/

Alternate agents include Trimethoprim-sulfamethoxazole 1 DS tablet BID x 3 days, cefixime 400 mg OD x 3 days or ciprofloxacin 250 mg BID or 500 mg XL form OD x 3 days.

Another new alternative (actually the re-appearance of an old drug) is fosfomycin. Fosfomycin is given as a single dose of 3 grams in powdered form mixed with water. I will write a post about fosfomycin soon.

Is it time to revisit cefepime?

We have recently done a small survey of peoples preferences for the therapy of AmpC – producing E. coli and below are the results. If you would like to take the survey click http://viha.fluidsurveys.com/s/UTI-Case-1/

Not long ago serious infections with E.coli and K. pneumoniae were treatable with a wide variety of antibiotics. The evolution of ESBL and AmpC producing strains has changed things. Now it is common in Canada to see infections with strains that are resistant to all of the “workhorse” hospital antibiotics (ceftriaxone, piperacillin-tazobactam, ciprofloxacin) making carbapenems the primary agents. Carbapenem use is rising and carbapenemase producing organisms are appearing on our shores – a very large concern.

Cefepime first became available in 1994 and was marketed as the first “4th generation” cephalosporin with a spectrum of activity similar to ceftazidime but with standard Q12H dosing. It is approved for the treatment of pneumonia, urinary tract infections, skin and soft-tissue infections, intra-abdominal infections and febrile neutropenia. Despite its broad label indications it has never been used widely in Canada. On the current BC provincial hospital formulary it is restricted to febrile neutropenia and cystic fibrosis.

Cefepime is the cephalosporin that is most stable to AmpC beta-lactamases of chromosomal or plasmid origin. There is growing clinical evidence of efficacy even in the context of hyperproduction of AmpC enzymes See http://cid.oxfordjournals.org/content/57/6/781.

With the only alternative therapy often being carbapenems, cefepime is being advocated as a “carbapenem-sparing” strategy for SPICE organism and AmpC E.coli, K. pneumonia and P. mirabilis infections.

It may be time to utilize cefepime more fully in BC.

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