These patients often represent “problem cases” in the
clinic. Frequently, different kinds of antibiotics are prescribed before the
patients are cured. In a few women, antibiotics have only a limited effect, but
most of these women are spontaneously cured after a varying time. Therefore , may refer her to an Urlogist if tr
under your care seems ineffective by two months time. The uncommon organism
responsible for recurrent urethritis in euglycemic women are 1) Mycoplasma genitalium: a common cause of persistent
urethritis more amongst men than women usually treated with doxycycline
2) Resistant Fungal. Infection 3) Urethral diverticulitis 4)
Trichomonal Urethritis .5) condom moistener covered over the outer aspect of
male condom 6) Contraceptive sponge / Pessary. However Doxycycline is the first
choice for treatment of non‐gonococcal urethritis (NGU)-à followed by
Azithromycin. According to current recommendations
treatment is initiated after establishing or excluding sexually transmitted
infection (STI) , How the lab diag of Rec urethritis is done . Treatment is
usually initiated when urethritis is diagnosed on the basis of microscopy of a
stained smear from the urethra. The number of polymorphonuclear leucocytes –WBC
(PMNLs) defining urethritis but usually >4 PMNLs per high power field
(×1000) (hpf) is considered significant. PMNL counts between
5/hpf and 10/hpf are often considered low grade or borderline, and can in some
patients represent a sign of infection, but may among other cases be normal.
Many researchers have time and again showed that the number of leucocytes
is a strong predictor of infection with Chlamydia
trachomatis although more than one third of the patients did
not have urethritis. In contrast, some studies showed that 90% of all patients
with C trachomatis or Mycoplasma
genitalium infection had urethritis and all of those with NGU (nongonococcal
) had >10 PMNLs/hpf.
Few points on Neisseria gonorrhoeae: It is a common cause of urethritis. However, gonorrhoea
has become a very uncommon disease in globally and not all reported though the
majority of the patients have NGU. B) Few points on the second common cause of rec urethritis C trachomatis
and this infection is on the rise. \ Though many studies reports
that more than half of the NGU patients
are C trachomatis negative.(nonspecific urethritis (NSU). C) . Few points on the Ureaplasmas may have a
role in some patients but its high isolation rate in men without urethritis has
given rise to much controversy. M
genitalium has been most thoroughly studied as a cause of
urethritis and cervicitis, but it is most likely also a cause of
upper genital tract infections. Tetracyclines are usually
suboptimal, whereas azithromycin is likely to be the most effective
antibiotic, when given as a total dose of 1.5 g over 5 days. Polymerase
chain reaction (PCR) tests detecting M
genitalium, which currently are the only diagnostic tools, have
recently been introduced
D) Few points on Trichomonas vaginalis might give rise to symptoms in
some patients whereas
E) Few points on M hominis.
,& M genitalium has
been shown to be an important aetiological agent in non‐chlamydial,
non‐gonococcal
urethritis (NCNGU) accounting for approximately 20% of symptomatic urethritis F) Few points on Viruses, such as adenovirus, herpes simplex,
and human papillomavirus, might be important in some cases, but the
majority remains unexplained
. Treatement
:--Doxycycline. The choice of antibiotic for NSU is usually the same as that
for NGU in general—that is, doxycycline. Despite appropriate antibiotic
therapy, 10%–20% of women return to the clinic because of persisting symptoms
and show signs of dysuria. Second
line drugs of Kochs for ordinary UTI!! What are second line drugs for Kochs ?? This group
of second line drugs is therefore considered to be the most important component
of the core MDR-TB regimen. The benefits from their use outweighs the potential
risks. So they should always be included unless there is an absolute
contra-indication for their use.
The order of preference for the inclusion of the later
generation fluoroquinolones in MDR-TB regimens is:
high-dose levofloxacin , all Fluoroquinolones
(levofloxacin or moxifloxacin), bed aquiline and linezolid are strongly
recommended for use in longer regimens, which are completed with other drugs
ranked by their relative balance of effectiveness to potential toxicity.
moxifloxacin
& gatifloxacin
It is recommended that ofloxacin is phased out from MDR-TB
regimens and that ciprofloxacin is never used due to the limited evidence for
their effectiveness Second Line Drugs - Fluoroquinolones,
second line injectable drugs
WHO recommendations on the treatment of drug resistant TB
In December 2018 the World Health Organisation (WHO) changed
their recommendations on the second line drugs to be used for the treatment of
drug resistant TB.1 As the treatment provided for many patients will lag
behind the guidelines produced by WHO, a summary of the 2016 recommendations
are also provided here for reference.
The guidelines published by WHO provide extensive information,
so the information provided here is just a summary.
Second line drugs, recommendations after December 2018
The second line drugs to be used for the treatment of drug
resistant TB after 2018 are shown in the table below.
The new guidelines mark a major change in the recommended
treatment to be provided for those on "longer regimens". Longer
MDR-TB regimens are treatments for MDR/RR-TB which last 18 months or more and
which may be standardized or individualized. These regimens are usually
designed to include a minimum number of second line TB medicines considered to
be effective based on patient history or drug resistance patterns. The term
"conventional" was previously used to refer to such regimens but was
discontinued in 2016 when WHO first issued a recommendation for the use of a
shorter MDR-TB regimen.
Injectable agents are no longer among the priority medicines to
be used when designing longer MDR-TB regimens and WHO recommends that oral
regimens should become the preferred option for most patients. It is a major
step forward in the treatment of patients with drug resistant TB that patients
are no longer required to have injectable drugs.
Fluoroquinolones (levofloxacin or moxifloxacin), bed aquiline
and linezolid are strongly recommended
for use in longer regimens, which are completed with other drugs ranked by
their relative balance of effectiveness to potential toxicity.
|
Group A :
|
Group B :
|
Group C :
|
|
Levofloxacin (Lfx) or
Moxifloxacin (Mfx) |
Clofazimine (Cfz)
|
Ethambutol (E)
|
|
Bedaquiline (Bdq)
|
Cycloserine (Cs)
or Terizidone (Trd) |
Delamanid (Dlm)
|
|
Linezolid (Lzd)
|
Pyrazinamide (Z)
|
|
|
Imipenem-cilastatin (Ipm-Cln) or
Meropenem (Mpm) |
||
|
Amikacin (Am) (or Streptomycin)
|
||
|
Ethionamide (Eto) or Prothionamide (Pto)
|
||
|
p-aminosalicylic acid (PAS)
|
||
|
Second line drugs used to treat rifampicin resistant
and multi drug resistant
TB after December 2018
|
||
If a plus sign is shown, clicking on it will show more columns.
All three medicines in Group A should be included.
In group B one or both medicines should be included
Group C medicines should be included to complete the regimen when medicines from Groups A and B cannot be used.
In group B one or both medicines should be included
Group C medicines should be included to complete the regimen when medicines from Groups A and B cannot be used.
There is some further information about this on the page on
the Treatment of Drug
Resistant TB, and there is extensive information which should be consulted
in the WHO guidelines document.
Second line drugs, recommendations after 2016 and before 2018
In 2016 WHO changed their recommendations on the second line
drugs to be used for the treatment of drug resistant TB.2. The
second line drugs to be used for the treatment of drug resistant TB after 2016
were as follows.
|
Group A : Fluoroquinolones
|
Group B : Second line injectable drugs
|
Group C : Other core second line drugs
|
Group D : Add-on drugs (not part of the core MDR-TB regimen)
|
|
Levofloxacin (Lfx)
|
Amikacin (Am)
|
Ethionamide/Prothionamide (Eto/Pto)
|
D1 Pyrazinamide
|
|
Moxifloxacin (Mfx)
|
Capreomycin (Cm)
|
Cycloserine / Terizidone (Cs Trd)
|
D1 Ethambutol (E)
|
|
Gatifloxacin (Gfx)
|
Kanamycin (Km)
|
Linezolid (Lzd)
|
D1 High-dose isoniazid (Hh)
|
|
(Streptomycin)
|
Clofazimine (Cfz)
|
D2 Bedaquiline (Bdq)
|
|
|
D2 Delamanid (Dlm)
|
|||
|
D3 p-aminosalicylic acid
PAS)
|
|||
|
D3 imipenem-cilastatin (lpm)
|
|||
|
D3 Meropenem (Mpm)
|
|||
|
D3 Amoxicillin-clavulanate (Amx-Clv)
|
|||
|
D3 Thioacetazone (T)
|
|||
Groups A, B & C are the core second line drugs.
If a plus sign is shown, clicking on it will show more columns.
Few points on Asymptomatic bacteriuria (ASB) : It is
worth remembering that Asymptomatic
bacteriuria (ASB) is the presence of bacteria within the urinary
tract, excluding the distal urethra, without signs or symptoms of infection.
ASB is associated with low-birth-weight infants and preterm delivery, and its
treatment in pregnancy is indicated. The prevalence of ASB during pregnancy
ranges from 2% to 7%. If left: untreated, 20% to 30% of ASB in pregnant women
progresses to pyelonephritis; treatment reduces this to 3%.
Screening for bacteriuria with a urine culture is
recommended at the first prenatal visit. Women with sickle cell trait have a
twofold increased risk of ASB and can be screened every trimester. A
clean-catch urine culture with >100,000 colonics/mL or catheterized urineculture
with >100 colonics/mL warrants treatment. Escherichia coli
accounts for 75% to 90% of infections. Klebsiella, Proteus, Pseudomonas, Enterobacter, and
coagulase-negative Staphylococcus are other common pathogens.
Initial therapy is usually empiric and may
be altered based on urine culture sensitivities. Repeat urine
culture is obtained 1 to 2 weeks after treatment and again each trimester. If
bacteriuria persists after two or more treatment courses, suppressive therapy
should be considered for the remainder of the pregnancy.
Acute cystitis occurs in approximately 1% to 3%
of pregnant women. Symptoms include urinary frequency, urgency, dysuria,
hematuria, and/or suprapubic discomfort. Empiric treatment regimens arc the
same as for ASB. If possible, a urine culture should be sent prior to
initiating antibiotic therapy.
Urethritis is usually caused by Chlamydia
trachomatis, and it should be suspected in patients with symptoms
of acute cystitis and a negative urine culture. Mucopurulent cervicitis may
also be present. The treatment of choice is azithromycin 1 g as a single oral
dose for both the patient and her partner. A test of cure should be sent 3 to 4
weeks after treatment.
Under certain conditions, covert bacteriuria can cause
symptomatic cystitis or pyelonephritis. Normal pregnancy-induced urinary stasis
and vesicoureteral reflux predispose to these infections. The invading
organisms are those from the normal perineal flora, and about 10% of women have
perineal colonization with strains of E. coli that have adhesins
such as S- or P-fimbriae. These appendages enhance bacterial virulence, and
indeed, 90% of E. coli isolates from women with acute
pyelonephritis have these fimbriae.
Because one-fourth of pregnant women with untreated
asymptomatic bacteriuria go on to develop acute pyelonephritis, early prenatal
screening and eradication is recommended by most, including the American
College of Obstetricians and Gynecologists. When the prevalence is low,
standard urine cultures may not be cost effective and other test systems such
as the dipstick culture technique have been reported to be accurate.
Cystitis typically is characterized by dysuria, urgency and
frequency with minimal manifestations. Infection is confirmed by pyuria,
hematuria and bacteriuria. The upper urinary tract may also become involved by
ascending infection, either with or without concomitant cystitis. The incidence
of acute pyelonephritis during pregnancy is reported to be as high as 4%.
Because of this, renal infection is a leading cause of sepsis syndrome (see
Protocol 26). Pyelonephritis is more common after midpregnancy and it is
right-sided in about half of cases and bilateral in another fourth. The onset
is usually abrupt with fever, shaking chills and pain in one or both lumbar
regions. There may be anorexia, nausea and vomiting. Tenderness usually can be
elicited by percussion in one or both costovertebral angles. The urinary
sediment usually contains many leukocytes, frequently in clumps, and numerous
bacteria. E.
coli strains are isolated from urine cultures in 75 to 80% of
women with pyelonephritis. The other isolates include Klebsiella,
Enterobacter or Proteus species or group B
streptococci. Women with acute pyelonephritis usually appear quite ill, and
bacteremia is confirmed in 15 to 20%.
Bacteriuria or cystitis are treated empirically with any of
several antimicrobial regimens that include single-dose or 3-day treatment
with ampicil- lin or amoxicillin; one of the cephalosporins or quinolones;
nitrofurantoin; or trimethoprim-sulfamethoxazole. Regardless of the regimen
chosen, the recurrence rate is about 30% after completion of any of these
regimens. For women with a recurrent infection, a second course with the same
or another one of these agents is given. For women with persistent bacteriuria,
or those with frequent recurrences, suppressive therapy for the remainder of
pregnancy can be given with nitrofurantoin, 100 mg at bedtime.
Most major complications encountered with antepartum
pyelonephritis are caused by the sepsis syndrome. Between 5 and 20% of women
will manifest reversible acute kidney injury manifest by elevated serum creatinine
levels. In some of these, it may be necessary to modify dosing with potentially
nephrotoxic antimicrobials such as amnioglycosides. Up to 5 to 10% of women
with acute pyelonephritis develop varying degrees of acute respiratory distress
syndrome. In some of these, tracheal intubation with mechanical ventilation is
lifesaving. After midpregnancy, septicemia may cause uterine activity, but
caution is urged for co-administration of tocolytics that may increase the risk
of permeability pulmonary edema. Finally, persistence of the sepsis syndrome
should prompt a search for ureteral obstruction as well as for a perinephric
phlegmon or abscess. Endotoxin-induced hemolysis causes anemia in about a third
of women.
A scheme for management of acute pyelonephritis during
pregnancy is shown in Table 41.1. Hydration with intravenous crystalloid
solutions and antimicrobials is the cornerstone of therapy and is begun
promptly at diagnosis. Therapy is empirical, and ampicillin plus gentamicin;
cefazolin or ceftriaxone; or an extended-spectrum beta-lactam have been found
to be 95% effective in randomized trials. Ongoing surveillance in an acute care
unit is recommended in order to recognize worsening of sepsis syndrome. To do
so, frequent determinations of vital signs and urinary output are monitored.
Clinical response is usually relatively prompt and clinical symptoms usually
resolve within 2 days and 95% of women are afebrile by 72 hours. As discussed,
for those who do not respond promptly and appropriately, consideration is given
for urinary tract obstruction, usually from stone disease, and imaging studies
may be indicated. At discharge, oral antimicrobial therapy is given for 7 to 10
days.
Recurrent covert bacteriuria develops in about a third of women
following treatment for pyelonephritis. Because a third of these will again
develop recurrent symptomatic infection, then asymptomatic bacteriuria is
treated again as
Management of the pregnant woman
with acute pyelonephritis
Hospitalization
Urine culture; blood culture if overtly septic
Hemogram, serum creatinine and electrolytes
Monitor vital signs frequently, including urinary output
with indwelling bladder catheter
Intravenous crystalloid to establish urinary output to
&50 ml/h
Intravenous antimicrobial therapy
Chest x-ray if there is dyspnea or tachypnea
Repeat hemogram and creatinine in 48 hours
Switch to oral antimicrobials when afebrile
Discharge when afebrile 24 hours,
give antimicrobial therapy for 7 to 10 days
Urine culture 1 to 2 weeks after antimicrobial therapy
completed
described above. Unless urine culture surveillance is
performed to ensure urine sterility, then nitrofurantoin, 100 mg at bedtime, is
given for the remainder of the pregnancy. Avoid using
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