Doxycycline for ESBL-E Cystitis | Clinical Infectious Diseases

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Tomasz Jodlowski,

Tomasz Jodlowski

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Charles R Ashby, Jr,

Charles R Ashby, Jr

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Sarath G Nath

Sarath G Nath

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Clinical Infectious Diseases, Volume 73, Issue 1, 1 July 2021, Pages e274–e275, https://doi. org/10.1093/cid/ciaa1898

Published:

29 December 2020

Article history

Published:

29 December 2020

Corrected and typeset:

16 February 2021

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To the Editor—With great anticipation we read the recently published ahead-of-print guidance on the treatment of antimicrobial resistant gram-negative infections by Tamma et al [1]. It is a very timely, well written, and useful document. However, we noticed the supporting reference for the statement: “Doxycycline is not recommended for the treatment of extended spectrum beta-lactamase—Enterobacterales (ESBL-E) cystitis due to limited urinary excretion,” on page 6. We do not support this statement as approximately 35%–60% of an oral dose of 100 mg of doxycycline dose is excreted unchanged into the urine [2]. The concentrations of doxycycline following a 100 mg oral dose in the urine can range from 60–300 μg/mL in patients with normal renal function, which is significantly greater than the MIC for the extended spectrum beta-lactamase (ESBL)-E that cause acute cystitis [3, 4].

Clinical data indicate that doxycycline has efficacy against susceptible Gram-positive uropathogens, such as Enterococcus faecalis and E. faecium including vancomycin-resistant E. fecium (VRE) and Gram-negative organisms, including E. coli and K. pneumoniae, that cause urinary cystitis [4–7] Additionally, it was also successful in eradication of VRE in the urine [8].

However, doxycycline is typically not used to treat urinary tract infections. This could be due to the fact that neither doxycycline nor tetracycline are always tested or reported against Gram-negative bacteria. There could also be a lack of knowledge regarding the concentrations reached in the urine that greatly exceed the MIC values for certain uropathogens. Its antimicrobial efficacy is increased in acidic environments, including urine [4]. Given the increased incidence in multidrug-resistant Gram-negative bacterial infections and the favorable pharmacokinetic and safety profile of doxycycline, perhaps its use for treating certain types of acute cystitis should be reconsidered. Following oral administration, 95% of a 100 mg dose of doxycycline is absorbed; doxycycline can be used in patients with renal insufficiency as there is a compensatory increase in nonrenal elimination [9]. Doxycycline is generally well tolerated and the most commonly reported adverse effects include nausea, vomiting, diarrhea, epigastric pain, photosensitivity reactions but the rate of treatment discontinuation is low. It has a low propensity for producing Clostridioides difficile infections [10], meanwhile a normal treatment course is relatively inexpensive. Doxycycline should not be given to pregnant females and children under the age of 8 due to the risk of permanent discoloration of developing teeth [5, 9]. Finally, doxycycline does not inhibit or induce any of the Phase I or II drug metabolizing enzymes, thus decreasing the likelihood of drug–drug interactions,

In conclusion, based on the published pharmacokinetic data and MIC values for uropathogenic ESBL-E, doxycycline reaches levels in the urine that should make it a potential option for the treatment of acute cystitis caused by ESBL-E.

Nonstandard Abbreviations

Nonstandard Abbreviations

 

• ESBL-E

  extended spectrum beta-lactamase Enterobacterales

 

• VRE

  vancomycin-resistant E. fecium

Note

Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

References

1.

Tamma

PD

,

Aitken

SL

,

Bonomo

RA

, et al. 

Infectious diseases society of America antimicrobial resistant treatment guidance: gram-negative bacterial infections

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Clin Infect Dis

2020

:ciaa1478. doi:10.1093/cid/ciaa1478.

2.

Agwuh

KN

,

MacGowan

A

.

Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines

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J Antimicrob Chemother

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65

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3.

Cunha

BA

.

Oral doxycycline for non-systemic urinary tract infections (UTIs) due to P. aeruginosa and other Gram negative uropathogens

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An infectious disease and pharmacokinetic perspective on oral antibiotic treatment of uncomplicated urinary tract infections due to multidrug-resistant Gram-negative uropathogens: the importance of urinary antibiotic concentrations and urinary pH

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White

CR

,

Jodlowski

TZ

,

Atkins

DT

,

Holland

NG

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Successful doxycycline therapy in a patient with Escherichia coli and multidrug-resistant Klebsiella pneumoniae urinary tract infection

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J Pharm Pract

2017

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464

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7

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6.

Lockey

JE

,

Williams

DN

,

Raij

L

,

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LD

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Comparison of 4 and 10 days of doxycycline treatment for urinary tract infection

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Holloway

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,

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Kim

Y

,

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S

,

Hwang

S

, et al. 

Does oral doxycycline treatment affect eradication of urine vancomycin-resistant Enterococcus? A tertiary hospital study

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Yeungnam Univ J Med

2020

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9.

Joshi

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© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

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Successful Doxycycline Therapy in a Patient With Escherichia coli and Multidrug-Resistant Klebsiella pneumoniae Urinary Tract Infection

Case Reports

. 2017 Aug;30(4):464-467.

doi: 10.1177/0897190016642362.

Epub 2016 Apr 12.

Cassandra R White 
^1
 
2
, Tomasz Z Jodlowski 
²
, Dylan T Atkins 
¹
, Nicole G Holland 
¹

Affiliations

Affiliations

• ¹ 1 Husson University School of Pharmacy, Bangor, ME, USA.
• ² 2 VA Maine Healthcare System, Augusta, ME, USA.

• PMID:

  27071978

• DOI:

  10. 1177/0897190016642362

Case Reports

Cassandra R White et al.

J Pharm Pract.

2017 Aug.

. 2017 Aug;30(4):464-467.

doi: 10.1177/0897190016642362.

Epub 2016 Apr 12.

Authors

Cassandra R White 
^1
 
2
, Tomasz Z Jodlowski 
²
, Dylan T Atkins 
¹
, Nicole G Holland 
¹

Affiliations

• ¹ 1 Husson University School of Pharmacy, Bangor, ME, USA.
• ² 2 VA Maine Healthcare System, Augusta, ME, USA.

• PMID:

  27071978

• DOI:

  10.1177/0897190016642362

Abstract

Objective:

To report on a patient with a symptomatic, polymicrobial Escherichia coli and multidrug-resistant (MDR), extended-spectrum β-lactamase (ESBL)-positive Klebsiella pneumoniae urinary tract infection (UTI) who was successfully treated with oral doxycycline hyclate.

Case summary:

A 70-year-old white male inpatient with a history of recurrent UTI, type 2 diabetes, hypertension, obesity, and diverticular disease was diagnosed with UTI and empirically treated with oral ciprofloxacin. Symptoms persisted 2 days later, and the patient was transitioned to amoxicillin/clavulanate by a different provider. The next day, upon receipt of the urine culture and susceptibility panel revealing E coli and MDR, ESBL-positive K pneumoniae infection, treatment was switched to doxycycline hyclate, which resulted in clinical improvement.

Discussion:

Complicated UTI involving multiple pathogens requires careful clinical judgment to select the appropriate antimicrobial agent, improve clinical outcomes, and prevent resistance. Treatment with doxycycline was based on the susceptibility panel and local resistance patterns. Advantages of doxycycline for UTI include its oral formulation, wide spectrum of activity, ability to achieve high concentration in the urine, and low toxicity.

Conclusion:

Doxycycline hyclate may be an effective treatment option for patients with susceptible MDR UTI.

Keywords:

bacterial resistance; doxycycline; infectious disease; urology.

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Cheap analogs of expensive antibiotics: analogs of expensive drugs

Antibiotics are one of the most expensive groups of drugs. And if the cost of “old” antibiotics is more or less acceptable, then new broad-spectrum antibiotics are incredibly expensive, which is not surprising, because the development of one new antibiotic costs approximately 1 billion US dollars.

If you think about this topic, you can understand that there are not so many new antibiotics, because not only do development and clinical studies take decades, but also the cost of the project is equal to the cost of space flight. In this regard, very few pharmaceutical companies in the US and Europe can conduct such expensive research.

For example, Linezolid (trade name Zyvox) is the latest antibiotic to enter the market and is patented by Pfizer. At the same time, it was synthesized back in 1990, and only in 2000 was it first put into practice.

And what about other pharmaceutical companies, including domestic ones, who cannot afford such expenses? The answer is simple – they produce generics, that is, analogues of already well-known antibiotics, with the same active ingredient as the original drug, but under a different trade name. The cost of such drugs is often lower than the cost of the original drug, but there are also opposite cases.

When prescribing antibiotic therapy, doctors can prescribe both the original drug – an expensive antibiotic (occurs less often), and its analogue – a cheap antibiotic (in most cases). The reason for this is the work of medical representatives of pharmaceutical companies and distributors. So if the doctor prescribed you an expensive antibiotic, do not rush to buy it at the expense of the budget. Most likely, he has a cheaper analogue, which a pharmacist in a pharmacy can also advise you if you ask him about it. However, it is worth remembering that from January 1, 2023 in Ukraine, you can buy an antibiotic only with an electronic prescription, which is pre-written to you by a doctor. The Doc.ua service also provides an opportunity to get an electronic prescription for antibiotics in just a few clicks. You can also buy all the necessary prescription drugs at the Doc.ua Pharmacy.

In this article we have provided a list of analogues of the most famous and widely used antibiotics.

Antibiotics for colds list Ukraine

Antibiotics of the penicillin group

Flemoxin Solutab , cases of bronchitis, sinusitis, pneumonia, peptic ulcer, cystitis and other

The average cost of Flemoxin Solutab and Ospamox is 80-150 UAH. Its analogue is Amoxil (amoxicillin analogues, amoxiclav analogues). The average cost is 50-70 UAH (inexpensive antibiotics for colds).

Antibiotics of the group of inhibitor-protected aminopenicillins

Flemoklav Solutab , Augmentin (amoxicillin and clavulanic acid).

This antibiotic is used to treat mild and uncomplicated cases of bronchitis, sinusitis, pneumonia, peptic ulcers, cystitis, etc. caused by b-lactamase producing bacteria.

The average cost of Flemoclav Solutab is 100-150 UAH, Augmentin is 130-190 UAH.

Flemoklav Solutab analogues, Augmentin analogues ( cheap broad-spectrum antibiotics):

Bactoclav is the cheapest antibiotic, the average price is 60 – 70 UAH.

Amoxil K, Medoklav, Abiklav, Amoksiklav 2x, Betaklav, are also inexpensive antibiotics for colds.

Antibiotics of the cephalosporin group

Emsef , Rotacef , Blitzef , Diacef , Denicef ​​ (ceftriaxone analogues in tablets) – Lorakson, Medakson (ceftriaxone analogue in tablets), Ceftriaxone-Darnitsa, Ceftriaxone-KMP, Ceftriaxone-Lekhim.

Antibiotics treat diseases such as sepsis, meningitis, disseminated Lyme borreliosis (early and late stages of the disease), infections of the abdominal cavity, etc. 27 (cefuroxime) – Aksetin, Aksef , Auroxetil.

Antibiotics treat urinary tract infections – cystitis, pyelonephritis, urethritis; skin and soft tissues – furunculosis, pyoderma, impetigo, etc.

Quadrocef , Roxipim , Abipim , Denipim 900 26, Exipim , Septipim (cefepime) – Cefepim-Lekhim, Cefepim Abryl, Cefepim Aurobindo.

Antibiotics treat respiratory diseases (pneumonia and bronchitis), urinary tract infections, and skin and soft tissue infections.

Eurosidim , Ceftazidime-Vista (ceftazidime) – Ceftazidime Yuria-pharm, Ceftum, Zacef, Ceftazidime-BHFZ.

These antibiotics are used to treat meningitis, sepsis and other illnesses.

Sorcef , Cefinac , Suprax Solutab (cefixime) – Lopraks, Opticef, Cefix.

Antibiotics treat diseases such as pharyngitis, tonsillitis, sinusitis, acute and chronic bronchitis, otitis media, and urinary tract infections.

Macrolide antibiotics

Sumamed , Azax , Azitrox , Aztec , Hemomycin , 9002 6 Zybax (azithromycin analogues are expensive, sumamed analogues) – Azibiot, Azipol, Zitrox, Ormax, Azimed (the best analogue sumamed) Azicin, Zoxy, Azithromycin-Astrapharm, Azithromycin-Health, Azithromycin-BHFZ, Azithromycin-Red Star, Ziomycin (azithromycin analogues of the drug).

These name antibiotics are used to treat pharyngitis, tonsillitis, sinusitis, otitis media, as well as acute bronchitis, pneumonia. 9Ora dro (clarithromycin analogs) – Aziklar, Clarithromycin-Health, Clarithromycin-Astrapharm, Clarithromycin-Darnitsa, Clarithromycin-Arterium, Clubax.

Antibiotics treat diseases such as infections of the upper respiratory tract and ENT organs: tonsillopharyngitis, otitis media, acute sinusitis, as well as infections of the lower respiratory tract: acute bronchitis, exacerbation of chronic bronchitis and others.

Antibiotics of the tetracycline group

Unidox Solutab (doxycycline) – its inexpensive antibiotics – analogues: Doxycycline-Teva, Doxycycline-Darnitsa, Doxycycline-BHFZ (inexpensive antibiotic).

Antibiotics are used to treat pharyngitis, bronchitis, tracheitis, bronchopneumonia, as well as otitis media, tonsillitis, sinusitis and others.

Antibacterial drugs of the fluoroquinolone group

Ofloxin (ofloxacin) – Ofloxacin-Darnitsa, Ofloxacin-Lekhim (inexpensive antibiotic).

Antibiotics treat infectious and inflammatory diseases of bones and joints, abdominal cavity, diseases of the kidneys (pyelonephritis) and urinary tract (cystitis, urethritis.

Abiflox , Levaksela, Lebel , Levoksimed, Levomak , Tigeron (levofloxacin) – Levokilz, Levofloxacin-Lekhim, Levofloxacin-Health, Floxium, Leflok.

Antibiotics are used to treat acute sinusitis, exacerbations of chronic bronchitis, community-acquired pneumonia, complicated urinary tract infections.

Avelox , Moxicum, Timoksi, Moxifloxacin-Sandoz (moxifloxacin) – Moxifloxacin-Lekhim, Moflaxa, Moxifloxacin-Pharmex, Atovax.

Antibiotics are used to treat acute sinusitis, exacerbations of chronic bronchitis, community-acquired pneumonia.

Cifran , Tsiprinol , Tsiprolet analogues , Flaprox, 900 26 Ciprobel (ciprofloxacin analogues are expensive) – Ciprofloxacin-Euro, Ciprofloxacin-Lekhim, Ciprofloxacin-Astrapharm, Citeral.

An antibiotic is used to treat sepsis and peritonitis and to prevent and treat infections in immunosuppressed patients.

Nitroimidazole antibacterials

Strong antibiotics in tablets

Trichopolum , Efloran (metronidazole) – Metrogyl, Metressa, Metronidazole-Health, Metronidazole-Darnitsa, Metronidazole-Infusion, Metronid Zol-Yuria Pharm, Metronidazole Lubnypharm.

Antibiotics treat protozoal infections: extraintestinal amoebiasis, including amoebic liver abscess, intestinal amoebiasis (amebic dysentery), trichomoniasis, giardiasis, balantidiasis, cutaneous leishmaniasis, trichomonas vaginitis, trichomonas urethritis, and others.

Ornigil , Ornizol, Ornimac (ornidazole) – Ornidazol-Darnitsa, Ornidazol-Novofarm, Ornidazol-Infusion.

Antibiotics are used to treat trichomoniasis, amoebiasis, giardiasis, and a mild antibiotic is used to prevent postoperative complications.

Antibiotic analogues table

Help DOC.ua: You can sign up for a consultation with a general practitioner on the website.

Urethritis | Dikul Center

Urethritis is a disease in which there is inflammation and irritation of the urethra, which is the passageway for urine from the bladder. Sperm also passes through the urethra in men.

Urethritis usually presents with pain when urinating and an urge to urinate frequently. The leading cause of urethritis is infection of the urethra by various bacteria.

Urethritis – differs from urinary tract infection in that the inflammation and infection affects only the urethra locally. The symptoms of a UTI may be the same as those of urethritis, but treatment will vary depending on the cause of the urethritis.

Urethritis can develop in people of any age and occurs in both women and men. However, women are at a higher risk of developing urethritis than men because the urethra is much shorter in women, which increases the risk of bacteria entering the urethra.

In 80% of cases, urethritis has a non-gonococcal origin.

Symptoms

Symptoms in men

Men with urethritis may have the following symptoms:

• Burning urination
• itching or burning sensation near the opening of the urethra
• blood in urine or semen
• discharge from the urethra

Symptoms in women

Women with urethritis may have the following symptoms:

• frequent urge to urinate
• urinary discomfort
• burning sensation or irritation in the area of ​​the urethral orifice
• possible abnormal discharge from the vagina.

At the same time, urethritis may be asymptomatic in some people, especially in women. In men, urethritis can also occur without symptoms if caused by infections such as chlamydia or Trichomonas.

For this reason, testing for (STIs) is essential when infections are suspected.

Causes

Most cases of urethritis are caused by infection: viruses or bacteria. The most common cause of urethritis is bacteria that can infect both the lining of the urethra and the bladder or kidneys. Bacteria that naturally live in the genital area can also cause urethritis if they enter the urinary tract.

Bacteria that can cause urethritis include:

• Neisseria gonorrhea
• Chlamydia trachomatis
• Mycoplasma genitalium

Urethritis can also be caused by protozoa such as trichomoniasis.

In addition, some viruses (human papillomavirus, herpes simplex and cytomegalovirus) can also cause urethritis.

Types

There are different types of urethritis classified according to the genesis of the inflammation. These are gonococcal urethritis and non-gonococcal urethritis.

Gonococcal urethritis is caused by the bacterium gonorrhea. Such an infection is the cause of urethritis in 20 percent of cases.

Non-gonococcal urethritis – not caused by gonorrhea, but by other infections. Chlamydia is a common cause of non-gonococcal urethritis, and other STIs can also cause inflammation of the urethra.

However, urethral irritation not associated with STIs may occur. These causes may be trauma to the genitals or, for example, damage to the urethra after using the catheter.

Urethritis can have multiple causes, especially in women.

Diagnosis

After your doctor has your symptoms and history, your doctor will also examine your genital area for discharge, tenderness, sores, and other signs of an STI. This can help the doctor make a diagnosis.

Your doctor may also order a urine or swab test from the urethra or vaginal area. If a specific STI is suspected, other blood tests may be ordered to look for other STIs, such as HIV and syphilis.

Within a few days, the results of the tests will be ready, and the doctor can prescribe treatment. Often, the partner also has to undergo examination and treatment.

Treatment

Urethritis is usually treated with medication, such as antibiotics or antivirals.

The most common drugs for treating urethritis are:

• azithromycin, an antibiotic, usually given as a single dose
• doxycycline
• erythromycin
• ofloxacin
• levofloxacin

If urethritis is caused by an STI, it is essential that all sexual partners be evaluated and treated if necessary. This helps to prevent re-infection and eliminate the risk of spreading STIs.

Symptoms usually improve within a few days of starting treatment. However, it is necessary to complete the fully recommended course of treatment and resume sexual activity no earlier than one week after completion of treatment.

Potential adverse effects may occur with drug interactions used to treat urethritis when taken with:

• blood thinners
• heart drugs
• anticonvulsants

Complications

Medications, if administered in time, allow you to quickly get rid of urethritis. However, if the infection is left untreated, the consequences can be long-term and very serious. The infection can spread to other parts of the urinary tract, including the bladder, ureters, and kidneys. If the urinary tract is affected, treatment is longer, and if left untreated, complications can be long-term and cause organ damage. Infections can also spread through the blood and lead to sepsis, which can be fatal.

In addition, STIs, which often cause urethritis, can cause problems with the reproductive system. Women can develop pelvic inflammatory disease (PID), which can cause infertility, pain during sex, or persistent pelvic pain. Women with untreated STIs also have a higher risk of ectopic pregnancy, which can be fatal.

In men, urethritis can lead to infection of the prostate or narrowing of the urethra due to scarring, resulting in painful urination. For these reasons, if you have any symptoms of urethritis, you should consult a doctor.

Prevention

Many of the bacteria that cause urethritis can be passed on to another person through sexual contact.